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Sökning: WFRF:(Hallström Björn)

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1.
  • Edfors, Fredrik, et al. (författare)
  • Gene-specific correlation of RNA and protein levels in human cells and tissues
  • 2016
  • Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292 .- 1744-4292. ; 12:10
  • Tidskriftsartikel (refereegranskat)abstract
    • An important issue for molecular biology is to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. Here, we have developed a targeted proteomics approach for a set of human non-secreted proteins based on parallel reaction monitoring to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP) conversion factor independent of the tissue type is introduced, thus significantly enhancing the predictability of protein copy numbers from RNA levels. The results show that the RTP ratio varies significantly with a few hundred copies per mRNA molecule for some genes to several hundred thousands of protein copies per mRNA molecule for others. In conclusion, our data suggest that transcriptome analysis can be used as a tool to predict the protein copy numbers per cell, thus forming an attractive link between the field of genomics and proteomics.
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2.
  • Hallström, Björn, et al. (författare)
  • Lund Stroke Register: hospitalization pattern and yield of different screening methods for first-ever stroke
  • 2007
  • Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 115:1, s. 49-54
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To explore case ascertainment, hospitalization, characteristics of both hospitalized and non-hospitalized patients in a population-based group of stroke patients. Materials and methods One-year screening in Lund-Orup district for first-ever strokes using multiple prospective and retrospective methods. Results A total of 456 patients with first-ever stroke (n = 412 prospective screening methods, n = 17 primary care, n = 12 hospital registers, n = 10 death register, n = 2 autopsy registers, n = 3 other). Hospitalization proportion within 14 days was 84%. Patients sent home from emergency unit (n = 36) were often males (75%), had low 28-day case-fatality (0%), and less severe strokes (median National Institute of Health Stroke Scale score 2 vs 4 for all). Patients managed solely within primary care (n = 18) were elderly (median age 89 vs 77 years for all), resided in nursing homes (86% vs 8% for all) and had high 28-day-case-fatality (61%). Conclusions Hospitalization was lower than expected. Two main categories of patients were not hospitalized: elderly patients at nursing homes with high case-fatality and patients with mild stroke.
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3.
  • Lindgren, Arne, et al. (författare)
  • Prevalence of Stroke and Vascular Risk Factors among First-Degree Relatives of Stroke Patients and Control Subjects.
  • 2005
  • Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 20:5, s. 381-387
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Genetic and environmental factors may be of importance for stroke risk. We assessed the prevalence of stroke and vascular risk factors among first-degree relatives and spouses of stroke patients and control subjects. <i>Methods:</i> As a part of the Lund Stroke Register study, we asked 925 consecutive patients with first-ever stroke and 286 control subjects to complete a questionnaire about all their first-degree relatives and spouses. The questionnaires addressed whether these relatives had been affected by stroke or TIA, hypertension, heart disease, diabetes mellitus, and if they were smokers. <i>Results:</i> A total of 606 patients and 261 control subjects returned the questionnaire, providing information on 4,972 first-degree relatives and 738 spouses. The prevalence of stroke or TIA was 12.3% among first-degree relatives of patients and 7.5% among first-degree relatives of control subjects (OR 1.74, 95% CI 1.36–2.22). Corresponding results for hypertension were 21.0 and 16.7% (OR 1.33, 95% CI 1.10–1.60). The prevalences of heart disease, diabetes mellitus and smoking did not differ significantly between first-degree relatives of patients and control subjects. Spouses of patients and control subjects had similar prevalences of stroke or TIA and vascular risk factors. <i>Conclusions:</i> The prevalences of stroke or TIA and hypertension are higher among first-degree relatives of stroke patients than among first-degree relatives of control subjects. This, and the lack of differences between spouses of patients and control subjects, indicates that an increased risk of stroke may in part be explained by heritability of hypertension.
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4.
  • Andersson, Sandra, et al. (författare)
  • The Transcriptomic and Proteomic Landscapes of Bone Marrow and Secondary Lymphoid Tissues
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12, s. e115911-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The sequencing of the human genome has opened doors for global gene expression profiling, and the immense amount of data will lay an important ground for future studies of normal and diseased tissues. The Human Protein Atlas project aims to systematically map the human gene and protein expression landscape in a multitude of normal healthy tissues as well as cancers, enabling the characterization of both housekeeping genes and genes that display a tissue-specific expression pattern. This article focuses on identifying and describing genes with an elevated expression in four lymphohematopoietic tissue types (bone marrow, lymph node, spleen and appendix), based on the Human Protein Atlas-strategy that combines high throughput transcriptomics with affinity-based proteomics. Results: An enriched or enhanced expression in one or more of the lymphohematopoietic tissues, compared to other tissue-types, was seen for 693 out of 20,050 genes, and the highest levels of expression were found in bone marrow for neutrophilic and erythrocytic genes. A majority of these genes were found to constitute well-characterized genes with known functions in lymphatic or hematopoietic cells, while others are not previously studied, as exemplified by C19ORF59. Conclusions: In this paper we present a strategy of combining next generation RNA-sequencing with in situ affinity-based proteomics in order to identify and describe new gene targets for further research on lymphatic or hematopoietic cells and tissues. The results constitute lists of genes with enriched or enhanced expression in the four lymphohematopoietic tissues, exemplified also on protein level with immunohistochemical images.
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5.
  • Anfelt, Josefine, et al. (författare)
  • Using Transcriptomics To Improve Butanol Tolerance of Synechocystis sp Strain PCC 6803
  • 2013
  • Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 79:23, s. 7419-7427
  • Tidskriftsartikel (refereegranskat)abstract
    • Cyanobacteria are emerging as promising hosts for production of advanced biofuels such as n-butanol and alkanes. However, cyanobacteria suffer from the same product inhibition problems as those that plague other microbial biofuel hosts. High concentrations of butanol severely reduce growth, and even small amounts can negatively affect metabolic processes. An understanding of how cyanobacteria are affected by their biofuel product can enable identification of engineering strategies for improving their tolerance. Here we used transcriptome sequencing (RNA-Seq) to assess the transcriptome response of Synechocystis sp. strain PCC 6803 to two concentrations of exogenous n-butanol. Approximately 80 transcripts were differentially expressed at 40 mg/liter butanol, and 280 transcripts were different at 1 g/liter butanol. Our results suggest a compromised cell membrane, impaired photosynthetic electron transport, and reduced biosynthesis. Accumulation of intracellular reactive oxygen species (ROS) scaled with butanol concentration. Using the physiology and transcriptomics data, we selected several genes for overexpression in an attempt to improve butanol tolerance. We found that overexpression of several proteins, notably, the small heat shock protein HspA, improved tolerance to butanol. Transcriptomics-guided engineering created more solvent-tolerant cyanobacteria strains that could be the foundation for a more productive biofuel host.
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6.
  • Árnason, Úlfur, et al. (författare)
  • The reversal of human phylogeny : Homo left Africa as erectus, came back as sapiens sapiens
  • 2020
  • Ingår i: Hereditas. - : Springer Science and Business Media LLC. - 0018-0661 .- 1601-5223. ; 157:1
  • Forskningsöversikt (refereegranskat)abstract
    • Background: The molecular out of Africa hypothesis, OOAH, has been considered as an established fact amid population geneticists for some 25–30 years despite the early concern with it among phylogeneticists with experience beyond that of Homo. The palaeontological support for the hypothesis is also questionable, a circumstance that in the light of expanding Eurasian palaeontological knowledge has become accentuated through the last decades. Results: The direction of evolution in the phylogenetic tree of modern humans (Homo sapiens sapiens, Hss) was established inter alia by applying progressive phylogenetic analysis to an mtDNA sampling that included a Eurasian, Lund, and the African Mbuti, San and Yoruba. The examination identified the African populations as paraphyletic, thereby compromising the OOAH. The finding, which was consistent with the out of Eurasia hypothesis, OOEH, was corroborated by the mtDNA introgression from Hss into Hsnn (Neanderthals) that demonstrated the temporal and physical Eurasian coexistence of the two lineages. The results are consistent with the palaeontologically established presence of H. erectus in Eurasia, a Eurasian divergence between H. sapiens and H. antecessor ≈ 850,000 YBP, an Hs divergence between Hss and Hsn (Neanderthals + Denisovans) ≈ 800,000 YBP, an mtDNA introgression from Hss into Hsnn* ≈ 500,000 YBP and an Eurasian divergence among the ancestors of extant Hss ≈ 250,000 YBP at the exodus of Mbuti/San into Africa. Conclusions: The present study showed that Eurasia was not the receiver but the donor in Hss evolution. The findings that Homo left Africa as erectus and returned as sapiens sapiens constitute a change in the understanding of Hs evolution to one that conforms to the extensive Eurasian record of Hs palaeontology and archaeology.
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7.
  • Bergman, Julia, et al. (författare)
  • The human adrenal gland proteome defined by transcriptomics and antibody-based profiling.
  • 2017
  • Ingår i: Endocrinology. - : Endocrine Society. - 0013-7227 .- 1945-7170. ; 158:2, s. 239-251
  • Tidskriftsartikel (refereegranskat)abstract
    • The adrenal gland is a composite endocrine organ with vital functions that include the synthesis and release of glucocorticoids and catecholamines. To define the molecular landscape that underlies the specific functions of the adrenal gland, we combined a genome-wide transcriptomics approach using messenger RNA sequencing of human tissues with immunohistochemistry-based protein profiling on tissue microarrays. Approximately two-thirds of all putative protein coding genes were expressed in the adrenal gland, and the analysis identified 253 genes with an elevated pattern of expression in the adrenal gland, with only 37 genes showing a markedly greater expression level (more than fivefold) in the adrenal gland compared with 31 other normal human tissue types analyzed. The analyses allowed for an assessment of the relative expression levels for well-known proteins involved in adrenal gland function but also identified previously poorly characterized proteins in the adrenal cortex, such as the FERM (4.1 protein, ezrin, radixin, moesin) domain containing 5 and the nephroblastoma overexpressed (NOV) protein homolog. We have provided a global analysis of the adrenal gland transcriptome and proteome, with a comprehensive list of genes with elevated expression in the adrenal gland and spatial information with examples of protein expression patterns for corresponding proteins. These genes and proteins constitute important starting points for an improved understanding of the normal function and pathophysiology of the adrenal glands.
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9.
  • Bidon, Tobias, et al. (författare)
  • Brown and Polar Bear Y Chromosomes Reveal Extensive Male-Biased Gene Flow within Brother Lineages
  • 2014
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 31:6, s. 1353-1363
  • Tidskriftsartikel (refereegranskat)abstract
    • Brown and polar bears have become prominent examples in phylogeography, but previous phylogeographic studies relied largely on maternally inherited mitochondrial DNA (mtDNA) or were geographically restricted. The male-specific Y chromosome, a natural counterpart to mtDNA, has remained underexplored. Although this paternally inherited chromosome is indispensable for comprehensive analyses of phylogeographic patterns, technical difficulties and low variability have hampered its application in most mammals. We developed 13 novel Y-chromosomal sequence and microsatellite markers from the polar bear genome and screened these in a broad geographic sample of 130 brown and polar bears. We also analyzed a 390-kb-long Y-chromosomal scaffold using sequencing data from published male ursine genomes. Y chromosome evidence support the emerging understanding that brown and polar bears started to diverge no later than the Middle Pleistocene. Contrary to mtDNA patterns, we found 1) brown and polar bears to be reciprocally monophyletic sister (or rather brother) lineages, without signals of introgression, 2) male-biased gene flow across continents and on phylogeographic time scales, and 3) male dispersal that links the Alaskan ABC islands population to mainland brown bears. Due to female philopatry, mtDNA provides a highly structured estimate of population differentiation, while male-biased gene flow is a homogenizing force for nuclear genetic variation. Our findings highlight the importance of analyzing both maternally and paternally inherited loci for a comprehensive view of phylogeographic history, and that mtDNA-based phylogeographic studies of many mammals should be reevaluated. Recent advances in sequencing technology render the analysis of Y-chromosomal variation feasible, even in nonmodel organisms.
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10.
  • Butler, L. M., et al. (författare)
  • Analysis of Body-wide Unfractionated Tissue Data to Identify a Core Human Endothelial Transcriptome
  • 2016
  • Ingår i: Cell Systems. - : Cell Press. - 2405-4712. ; 3:3, s. 287-301.e3
  • Tidskriftsartikel (refereegranskat)abstract
    • Endothelial cells line blood vessels and regulate hemostasis, inflammation, and blood pressure. Proteins critical for these specialized functions tend to be predominantly expressed in endothelial cells across vascular beds. Here, we present a systems approach to identify a panel of human endothelial-enriched genes using global, body-wide transcriptomics data from 124 tissue samples from 32 organs. We identified known and unknown endothelial-enriched gene transcripts and used antibody-based profiling to confirm expression across vascular beds. The majority of identified transcripts could be detected in cultured endothelial cells from various vascular beds, and we observed maintenance of relative expression in early passage cells. In summary, we describe a widely applicable method to determine cell-type-specific transcriptome profiles in a whole-organism context, based on differential abundance across tissues. We identify potential vascular drug targets or endothelial biomarkers and highlight candidates for functional studies to increase understanding of the endothelium in health and disease.
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11.
  • Carreras-Puigvert, Jordi, et al. (författare)
  • A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family
  • 2017
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes. To a certain extent, their substrate preference redundancies correlate with structural classes, thus linking structure and activity relationships. To elucidate interdependence among the NUDIX hydrolases, we pairwise deplete them generating an epistatic interaction map, evaluate cell cycle perturbations upon knockdown in normal and cancer cells, and analyse their protein and mRNA expression in normal and cancer tissues. Using a novel FUSION algorithm, we integrate all data creating a comprehensive NUDIX enzyme profile map, which will prove fundamental to understanding their biological functionality.
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12.
  • Caspeta-Guadarrama, Luis, 1974, et al. (författare)
  • Altered sterol composition renders yeast thermotolerant
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6205, s. 75-78
  • Tidskriftsartikel (refereegranskat)abstract
    • Ethanol production for use as a biofuel is mainly achieved through simultaneous saccharification and fermentation by yeast. Operating at >= 40 degrees C would be beneficial in terms of increasing efficiency of the process and reducing costs, but yeast does not grow efficiently at those temperatures. We used adaptive laboratory evolution to select yeast strains with improved growth and ethanol production at >= 40 degrees C. Sequencing of the whole genome, genome-wide gene expression, and metabolic-flux analyses revealed a change in sterol composition, from ergosterol to fecosterol, caused by mutations in the C-5 sterol desaturase gene, and increased expression of genes involved in sterol biosynthesis. Additionally, large chromosome III rearrangements and mutations in genes associated with DNA damage and respiration were found, but contributed less to the thermotolerant phenotype.
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13.
  • Danielsson, Angelika, et al. (författare)
  • The Human Pancreas Proteome Defined by Transcriptomics and Antibody-Based Profiling
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12, s. e115421-
  • Tidskriftsartikel (refereegranskat)abstract
    • The pancreas is composed of both exocrine glands and intermingled endocrine cells to execute its diverse functions, including enzyme production for digestion of nutrients and hormone secretion for regulation of blood glucose levels. To define the molecular constituents with elevated expression in the human pancreas, we employed a genome-wide RNA sequencing analysis of the human transcriptome to identify genes with elevated expression in the human pancreas. This quantitative transcriptomics data was combined with immunohistochemistry-based protein profiling to allow mapping of the corresponding proteins to different compartments and specific cell types within the pancreas down to the single cell level. Analysis of whole pancreas identified 146 genes with elevated expression levels, of which 47 revealed a particular higher expression as compared to the other analyzed tissue types, thus termed pancreas enriched. Extended analysis of in vitro isolated endocrine islets identified an additional set of 42 genes with elevated expression in these specialized cells. Although only 0.7% of all genes showed an elevated expression level in the pancreas, this fraction of transcripts, in most cases encoding secreted proteins, constituted 68% of the total mRNA in pancreas. This demonstrates the extreme specialization of the pancreas for production of secreted proteins. Among the elevated expression profiles, several previously not described proteins were identified, both in endocrine cells (CFC1, FAM159B, RBPJL and RGS9) and exocrine glandular cells (AQP12A, DPEP1, GATM and ERP27). In summary, we provide a global analysis of the pancreas transcriptome and proteome with a comprehensive list of genes and proteins with elevated expression in pancreas. This list represents an important starting point for further studies of the molecular repertoire of pancreatic cells and their relation to disease states or treatment effects.
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14.
  • Derwig, Mariette, et al. (författare)
  • eHealth usage among parents to premature or surgically treated neonates: associations with eHealth literacy, healthcare satisfaction or satisfaction with an eHealth device
  • 2023
  • Ingår i: BMC Pediatrics. - 1471-2431. ; 23
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundA specific eHealth device, a surf tablet, was developed for bridging between advanced in-hospital care and children’s homes. Since little is known about determinators for parental eHealth usage, the study’s aim was to explore if parents’ usage of the device was associated with their eHealth literacy, or their satisfaction with their child’s healthcare or with the specific surf tablet.MethodsIn this explorative usage and questionnaire study, parents to neonates who were discharged home after advanced in-hospital care were included. Their surf tablet usage at maximum 30 days after discharge was reported as frequency (%) of active days (usage days/days having the device) and median number of tablet activities (chat and photo) per usage day. eHealth literacy (eHealth Literacy Questionnaire; eHLQ), healthcare satisfaction (PedsQL Healthcare Satisfaction Generic Module), and satisfaction with the surf tablet were explored regarding tablet usage. Statistics were described in median (range) and (%) using non-parametric and regression models (p ResultsParents to 32 children (11 premature, 21 operated) were included. Active days with eHealth communication using the device was 39% (9.0/29.5), with 2.0 (1.0-4.2) usage occasions per active day. Activity on the tablet was higher among parents reporting to be very satisfied or satisfied with the device (n = 25) compared with neutral/dissatisfied parents (n = 7) (2.8 vs. 2.2 vs. 1.6 activities) (p = 0.030), while their frequency of active days did not differ (31.6% vs. 38.3% vs. 40%) (p = 0.963). A higher eHealth literacy was not associated with frequency of active days (0.926 (0.652–1.317); p = 0.659) or number of eHealth activities (0.973 (0.758–1.250); p = 0.825). Healthcare satisfaction was not associated with higher frequency of active days 0.996 (0.983–1.009; p = 0.519); neither was number of eHealth activities 1.001 (0.991–1.011; p = 0.883).ConclusionIn this study, eHealth usage was associated with parental satisfaction with the specific eHealth device, but not with eHealth literacy or healthcare satisfaction. To assure equal access to healthcare when using eHealth, the user-friendliness of the device seems to be crucial, and technical support needs to be in place.
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15.
  • Djureinovic, Dijana, et al. (författare)
  • Profiling cancer testis antigens in non-small-cell lung cancer
  • 2016
  • Ingår i: JCI INSIGHT. - : American Society for Clinical Investigation. - 2379-3708. ; 1:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.
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16.
  • Djureinovic, Dijana, et al. (författare)
  • The human testis-specific proteome defined by transcriptomics and antibody-based profiling
  • 2014
  • Ingår i: Molecular human reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 20:6, s. 476-488
  • Tidskriftsartikel (refereegranskat)abstract
    • The testis' function is to produce haploid germ cells necessary for reproduction. Here we have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling to characterize the molecular components of the testis. Deep sequencing (RNA-Seq) of normal human testicular tissue from seven individuals was performed and compared with 26 other normal human tissue types. All 20 050 putative human genes were classified into categories based on expression patterns. The analysis shows that testis is the tissue with the most tissue-specific genes by far. More than 1000 genes show a testis-enriched expression pattern in testis when compared with all other analyzed tissues. Highly testis enriched genes were further characterized with respect to protein localization within the testis, such as spermatogonia, spermatocytes, spermatids, sperm, Sertoli cells and Leydig cells. Here we present an immunohistochemistry-based analysis, showing the localization of corresponding proteins in different cell types and various stages of spermatogenesis, for 62 genes expressed at > 50-fold higher levels in testis when compared with other tissues. A large fraction of these genes were unexpectedly expressed in early stages of spermatogenesis. In conclusion, we have applied a genome-wide analysis to identify the human testis-specific proteome using transcriptomics and antibody-based protein profiling, providing lists of genes expressed in a tissue-enriched manner in the testis. The majority of these genes and proteins were previously poorly characterised in terms of localization and function, and our list provides an important starting point to increase our molecular understanding of human reproductive biology and disease.
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18.
  • Dusart, Philip, et al. (författare)
  • A Systems-Based Map of Human Brain Cell-Type Enriched Genes and Malignancy-Associated Endothelial Changes
  • 2019
  • Ingår i: Cell Reports. - : CELL PRESS. - 2211-1247. ; 29:6, s. 1690-
  • Tidskriftsartikel (refereegranskat)abstract
    • Changes in the endothelium of the cerebral vasculature can contribute to inflammatory, thrombotic, and malignant disorders. The importance of defining cell-type-specific genes and their modification in disease is increasingly recognized. Here, we develop a bioinformatics-based approach to identify normal brain cell-enriched genes, using bulk RNA sequencing (RNA-seq) data from 238 normal human cortex samples from 2 independent cohorts. We compare endothelial cell-enriched gene profiles with astrocyte, oligodendrocyte, neuron, and microglial cell profiles. Endothelial changes in malignant disease are explored using RNA-seq data from 516 lower-grade gliomas and 401 glioblastomas. Lower-grade gliomas appear to be an "endothelial intermediate'' between normal brain and glioblastoma. We apply our method for the prediction of glioblastoma-specific endothelial biomarkers, providing potential diagnostic or therapeutic targets. In summary, we provide a roadmap of endothelial cell identity in normal and malignant brain, using a method developed to resolve bulk RNA-seq into constituent cell-type-enriched profiles.
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19.
  • Eraslan, Basak, et al. (författare)
  • Quantification and discovery of sequence determinants of protein-per-mRNA amount in 29 human tissues
  • 2019
  • Ingår i: Molecular Systems Biology. - : WILEY. - 1744-4292 .- 1744-4292. ; 15:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite their importance in determining protein abundance, a comprehensive catalogue of sequence features controlling protein-to-mRNA (PTR) ratios and a quantification of their effects are still lacking. Here, we quantified PTR ratios for 11,575 proteins across 29 human tissues using matched transcriptomes and proteomes. We estimated by regression the contribution of known sequence determinants of protein synthesis and degradation in addition to 45 mRNA and 3 protein sequence motifs that we found by association testing. While PTR ratios span more than 2 orders of magnitude, our integrative model predicts PTR ratios at a median precision of 3.2-fold. A reporter assay provided functional support for two novel UTR motifs, and an immobilized mRNA affinity competition-binding assay identified motif-specific bound proteins for one motif. Moreover, our integrative model led to a new metric of codon optimality that captures the effects of codon frequency on protein synthesis and degradation. Altogether, this study shows that a large fraction of PTR ratio variation in human tissues can be predicted from sequence, and it identifies many new candidate post-transcriptional regulatory elements.
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20.
  • Fagerberg, Linn, et al. (författare)
  • Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
  • 2014
  • Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
  • Tidskriftsartikel (refereegranskat)abstract
    • Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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21.
  • Fletcher, Eugene, 1986, et al. (författare)
  • Evolutionary engineering reveals divergent paths when yeast is adapted to different acidic environments
  • 2017
  • Ingår i: Metabolic engineering. - : Academic Press. - 1096-7176 .- 1096-7184. ; 39, s. 19-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Tolerance of yeast to acid stress is important for many industrial processes including organic acid production. Therefore, elucidating the molecular basis of long term adaptation to acidic environments will be beneficial for engineering production strains to thrive under such harsh conditions. Previous studies using gene expression analysis have suggested that both organic and inorganic acids display similar responses during short term exposure to acidic conditions. However, biological mechanisms that will lead to long term adaptation of yeast to acidic conditions remains unknown and whether these mechanisms will be similar for tolerance to both organic and inorganic acids is yet to be explored. We therefore evolved Saccharomyces cerevisiae to acquire tolerance to HCl (inorganic acid) and to 0.3 M L-lactic acid (organic acid) at pH 2.8 and then isolated several low pH tolerant strains. Whole genome sequencing and RNA-seq analysis of the evolved strains revealed different sets of genome alterations suggesting a divergence in adaptation to these two acids. An altered sterol composition and impaired iron uptake contributed to HCl tolerance whereas the formation of a multicellular morphology and rapid lactate degradation was crucial for tolerance to high concentrations of lactic acid. Our findings highlight the contribution of both the selection pressure and nature of the acid as a driver for directing the evolutionary path towards tolerance to low pH. The choice of carbon source was also an important factor in the evolutionary process since cells evolved on two different carbon sources (raffinose and glucose) generated a different set of mutations in response to the presence of lactic acid. Therefore, different strategies are required for a rational design of low pH tolerant strains depending on the acid of interest.
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22.
  • Funkquist, Eva-Lotta, 1965- (författare)
  • Policies and Practice in Neonatal Nursing Related to Nutrition
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of these studies was to increase knowledge about hospital feeding routines in high-risk neonates. A retrospective medical chart review procedure was used to study routines at the neonatal units of two Swedish hospitals. In Papers I and II, the sample (Uppsala n=21 and Umeå n=21) comprised of small for gestational age (SGA) infants, in Papers III (Uppsala n=64 and Umeå n=59) and IV (n=127), the samples comprised of appropriate for gestational age (AGA) infants. Paper I indicated large enteral/oral milk volumes rendered i.v. administration of glucose unnecessary, reduced weight loss and helped SGA infants regain birth weight earlier. More rapid postnatal growth did not remain up to 18 months with corrected age in any growth variable (Paper II). In Paper III, effects were compared whether the infants’ volume of breast milk intake in hospital was estimated by “clinical indices” or determined by test-weighing. Infants treated in hospitals where test-weighing was practised attained exclusive breastfeeding at an earlier postmenstrual age (PMA), and they were discharged at an earlier PMA. However, the two study units were similar regarding the proportion of infants attaining exclusive breastfeeding. Paper IV revealed preterm AGA infants with higher standard deviation scores (SDS) at birth had more negative changes from birth to discharge for all growth variables. Conclusions: Papers I and II indicated that early initiation of enteral/oral feeding with proactive increases in milk volume was beneficial short term. No evidence was found for a proactive nutrition regimen with initial large volumes of milk resulting in a different pattern of growth up to the corrected age of 18 months. Test-weighing before and after breastfeeding might help infants to attain exclusive breastfeeding at an earlier PMA (study III). Finally, preterm AGA infants with higher SDS at birth are at higher risk of inadequate growth during their hospital stay (study IV).
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23.
  • Gallus, S., et al. (författare)
  • Evolutionary histories of transposable elements in the genome of the largest living marsupial carnivore, the tasmanian devil
  • 2015
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 32:5, s. 1268-1283
  • Tidskriftsartikel (refereegranskat)abstract
    • The largest living carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii), is the sole survivor of a lineage originating about 12 Ma. We set out to investigate the spectrum of transposable elements found in the Tasmanian devil genome, the first high-coverage genome of an Australian marsupial. Marsupial genomes have been shown to have the highest amount of transposable elements among vertebrates. We analyzed the horizontally transmitted DNA transposons OC1 and hAT-1-MEu in the Tasmanian devil genome. OC1 is present in all carnivorous marsupials, while having a very limited distribution among the remaining Australian marsupial orders. In contrast, hAT-1-MEu is present in all Australian marsupial orders, and has so far only been identified in a few placental mammals. We screened 158 introns for phylogenetically informative retrotransposons in the order Dasyuromorphia, and found that the youngest SINE (Short INterspersed Element), WSINE1, is no longer active in the subfamily Dasyuridae. The lack of detectable WSINE1 activity in this group may be due to a retrotransposon inactivation event approximately 30 Ma. We found that the Tasmanian devil genome contains a relatively low number of continuous full-length LINE-1 (Long INterspersed Element 1, L1) retrotransposons compared with the opossum genome. Furthermore, all L1 elements in the Tasmanian devil appeared to be nonfunctional. Hidden Markov Model approaches suggested that other potential sources of functional reverse transcriptase are absent from the genome. We discuss the issues associated with assembling long, highly similar L1 copies from short read Illumina data and describe how assembly artifacts can potentially lead to erroneous conclusions.
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24.
  • Gremel, Gabriela, et al. (författare)
  • The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling
  • 2015
  • Ingår i: Journal of gastroenterology. - : Springer. - 0944-1174 .- 1435-5922. ; 50:1, s. 46-57
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The gastrointestinal tract (GIT) is subdivided into different anatomical organs with many shared functions and characteristics, but also distinct differences. We have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling to describe the gene and protein expression patterns that define the human GIT. METHODS: RNA sequencing data derived from stomach, duodenum, jejunum/ileum and colon specimens were compared to gene expression levels in 23 other normal human tissues analysed with the same method. Protein profiling based on immunohistochemistry and tissue microarrays was used to sub-localize the corresponding proteins with GIT-specific expression into sub-cellular compartments and cell types. RESULTS: Approximately 75% of all human protein-coding genes were expressed in at least one of the GIT tissues. Only 51 genes showed enriched expression in either one of the GIT tissues and an additional 83 genes were enriched in two or more GIT tissues. The list of GIT-enriched genes with validated protein expression patterns included various well-known but also previously uncharacterised or poorly studied genes. For instance, the colon-enriched expression of NXPE family member 1 (NXPE1) was established, while NLR family, pyrin domain-containing 6 (NLRP6) expression was primarily found in the human small intestine. CONCLUSIONS: We have applied a genome-wide analysis based on transcriptomics and antibody-based protein profiling to identify genes that are expressed in a specific manner within the human GIT. These genes and proteins constitute important starting points for an improved understanding of the normal function and the different states of disease associated with the GIT.
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25.
  • Habuka, Masato, et al. (författare)
  • The Kidney Transcriptome and Proteome Defined by Transcriptomics and Antibody-Based Profiling
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12, s. e116125-
  • Tidskriftsartikel (refereegranskat)abstract
    • To understand renal functions and disease, it is important to define the molecular constituents of the various compartments of the kidney. Here, we used comparative transcriptomic analysis of all major organs and tissues in the human body, in combination with kidney tissue micro array based immunohistochemistry, to generate a comprehensive description of the kidney-specific transcriptome and proteome. A special emphasis was placed on the identification of genes and proteins that were elevated in specific kidney subcompartments. Our analysis identified close to 400 genes that had elevated expression in the kidney, as compared to the other analysed tissues, and these were further subdivided, depending on expression levels, into tissue enriched, group enriched or tissue enhanced. Immunohistochemistry allowed us to identify proteins with distinct localisation to the glomeruli (n=11), proximal tubules (n=120), distal tubules (n=9) or collecting ducts (n=8). Among the identified kidney elevated transcripts, we found several proteins not previously characterised or identified as elevated in kidney. This description of the kidney specific transcriptome and proteome provides a resource for basic and clinical research to facilitate studies to understand kidney biology and disease.
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26.
  • Haglund, Felix, et al. (författare)
  • Inflammatory infiltrates in parathyroid tumors
  • 2017
  • Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 177:6, s. 445-453
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Inflammatory infiltrates are sometimes present in solid tumors and may be coupled to clinical behavior or etiology. Infectious viruses contribute to tumorigenesis in a significant fraction of human neoplasias. Objective: Characterize inflammatory infiltrates and possible viral transcription in primary hyperparathyroidism. Design: From the period 2007 to 2016, a total of 55 parathyroid tumors (51 adenomas and 4 hyperplasias) with prominent inflammatory infiltrates were identified from more than 2000 parathyroid tumors in the pathology archives, and investigated by immunohistochemistry for CD4, CD8, CD20 and CD45 and scored as +0, +1 or +2. Clinicopathological data were compared to 142 parathyroid adenomas without histological evidence of inflammation. Transcriptome sequencing was performed for 13 parathyroid tumors (four inflammatory, 9 non-inflammatory) to identify potential viral transcripts. Results: Tumors had prominent germinal center-like nodular (+2) lymphocytic infiltrates consisting of T and B lymphocytes (31%) and/or diffuse (+1-2) infiltrates of predominantly CD8+T lymphocytes (84%). In the majority of cases with adjacent normal parathyroid tissue, the normal rim was unaffected by the inflammatory infiltrates (96%). Presence of inflammatory infiltrates was associated with higher levels of serum-PTH (P = 0.007) and oxyphilic differentiation (P = 0.002). Co-existent autoimmune disease was observed in 27% of patients with inflammatory infiltrates, which in turn was associated with oxyphilic differentiation (P = 0.041). Additionally, prescription of anti-inflammatory drugs was associated with lower serum ionized calcium (P = 0.037). Conclusions: No evidence of virus-like sequences in the parathyroid tumors could be found by transcriptome sequencing, suggesting that other factors may contribute to attract the immune system to the parathyroid tumor tissue.
  •  
27.
  • Hailer, F., et al. (författare)
  • Response to comment on "Nuclear genomic sequences reveal that polar bears are an old and distinct bear lineage"
  • 2013
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 340:6127, s. 1522-b
  • Tidskriftsartikel (refereegranskat)abstract
    • Nakagome et al. reanalyzed some of our data and assert that we cannot refute the mitochondrial DNA-based scenario for polar bear evolution. Their single-locus test statistic is strongly affected by introgression and incomplete lineage sorting, whereas our multilocus approaches are better suited to recover the true species relationships. Indeed, our sister-lineage model receives high support in a Bayesian model comparison.
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28.
  • Hallström, Björn, et al. (författare)
  • Gnathostome phylogenomics utilizing lungfish EST sequences.
  • 2009
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 26:2, s. 463-471
  • Tidskriftsartikel (refereegranskat)abstract
    • The relationship between the Chondrichthyes (cartilaginous fishes), the Actinopterygii (ray-finned fishes) and the piscine Sarcopterygii (lobe-finned fishes), and how the Tetrapoda (four-limbed terrestrial vertebrates) are related to these has been a contentious issue for more than a century. A general consensus about the relationship of these vertebrate clades has gradually emerged among morphologists, but no molecular study has yet provided conclusive evidence for any specific hypothesis. In order to examine these relationships on the basis of more extensive sequence data we have produced almost 1,000,000 base pairs of expressed sequence tags (ESTs) from the African marbled lungfish, Protopterus aethiopicus. This new data set yielded 771 transcribed nuclear sequences that had not been previously described. The lungfish EST sequences were combined with EST data from two cartilaginous fishes and whole genome data from an agnathan, four ray-finned fishes and four tetrapods. Phylogenomic analysis of these data yielded, for the first time, significant maximum likelihood support for a traditional gnathostome tree with a split between the Chondrichthyes and remaining (bone) gnathostomes. Also the sister group relationship between Dipnoi (lungfishes) and Tetrapoda received conclusive support. Previously proposed hypotheses, such as the monophyly of fishes, could be rejected significantly. The divergence time between lungfishes and tetrapods was estimated to 382-390 million years ago by the current data set and six calibration points.
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29.
  • Hallström, Björn, et al. (författare)
  • Mammalian evolution may not be strictly bifurcating.
  • 2010
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 27, s. 2804-2816
  • Tidskriftsartikel (refereegranskat)abstract
    • The massive amount of genomic sequence data that is now available for analyzing evolutionary relationships among 31 placental mammals reduces the stochastic error in phylogenetic analyses to virtually zero. One would expect that this would make it possible to finally resolve controversial branches in the placental mammalian tree. We analyzed a 2,863,797 nucleotide-long alignment (3,364 genes) from 31 placental mammals for reconstructing their evolution. Most placental mammalian relationships were resolved, and a consensus of their evolution is emerging. However, certain branches remain difficult or virtually impossible to resolve. These branches are characterized by short divergence times in the order of 1-4 million years. Computer simulations based on parameters from the real data show that as little as about 12,500 amino acid sites could be sufficient to confidently resolve short branches as old as about 90 million years ago. Thus, the amount of sequence data should no longer be a limiting factor in resolving the relationships among placental mammals. The timing of the early radiation of placental mammals coincides with a period of climate warming some 100 - 80 million years ago and with continental fragmentation. These global processes may have triggered the rapid diversification of placental mammals. However, the rapid radiations of certain mammalian groups complicate phylogenetic analyses, possibly due to incomplete lineage sorting and introgression. These speciation-related processes led to a mosaic genome and conflicting phylogenetic signals. Split network methods are ideal for visualizing these problematic branches and can therefore depict data conflict and possibly the true evolutionary history better than strictly bifurcating trees. Given the timing of tectonics, of placental mammalian divergences, and the fossil record, a Laurasian rather than Gondwanan origin of placental mammals seems the most parsimonious explanation.
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30.
  • Hallström, Björn (författare)
  • Phylogenomic Analysis of Vertebrate Evolution
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The field of phylogenomics has emerged during the last five years, as the number of fully or partially sequenced genomes has increased rapidly. Using whole genomes for phylogenetic studies greatly increases the accuracy of the trees determined, and can potentially resolve phylogenetic questions that could not be resolved bu studies using only a few gene sequences. In the current thesis selected phylogentic problems in vertebrate evolution has been studies, with special emphasis on placental mammals. Sequences from several thousand protein-coding sequences (representing almost 3 million nucleotide characters) have been compared between over 30 species of placental mammals. The need for novel bioinformatical methods and approaches to work with such large amounts of data has been solved with customised software. The large-scale analyses has resolved several previously uncertain relationships with strong statistical confidence. However, a small number of divergences remained unresolved, despite the extensive data sampling. As other possibilities were ruled out as less likely, the natural explanation for this lack of resolution is probably to be found in speciation related processes. All the identified problematic relationships are characterised by rapid subsequent speciation events. In such scenarios, incomplete sorting of ancient polymorphism and species hybridization are processes that could create mosaic genomes in which different parts of the genomes will show incompatible trees. Divergences such as these are not well-represented as a classic bifurcating tree, instead attempts to illustrate them as phylogenetic networks have been made to more accurately describe the speciation.
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31.
  • Hallström, Björn, et al. (författare)
  • Phylogenomic data analyses provide evidence that Xenarthra and Sfrotheria are sister groups
  • 2007
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 24:9, s. 2059-2068
  • Tidskriftsartikel (refereegranskat)abstract
    • The phylogenetic positions of the 4 clades, Euarchontoglires, Laurasiatheria, Afrotheria, and Xenarthra, have been major issues in the recent discussion of basal relationships among placental mammals. However, despite considerable efforts these relationships, crucial to the understanding of eutherian evolution and biogeography, have remained essentially unresolved. Euarchontoglires and Laurasiatheria are generally joined into a common clade (Boreoeutheria), whereas the position of Afrotheria and Xenarthra relative to Boreoeutheria has been equivocal in spite of the use of comprehensive amounts of nuclear encoded sequences or the application of genome-level characters such as retroposons. The probable reason for this uncertainty is that the divergences took place long time ago and within a narrow temporal window, leaving only short common branches. With the aim of further examining basal eutherian relationships, we have collected conserved protein-coding sequences from 11 placental mammals, a marsupial and a bird, whose nuclear genomes have been largely sequenced. The length of the alignment of homologous sequences representing each individual species is 2,168,859 nt. This number of sites, representing 2840 protein-coding genes, exceeds by a considerable margin that of any previous study. The phylogenetic analysis joined Xenarthra and Afrotheria on a common branch, Attantogenata. This topology was found to fit the data significantly better than the alternative trees.
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32.
  • Hallström, Björn, et al. (författare)
  • Resolution among major placental mammal interordinal relationships with genome data imply that speciation influenced their earliest radiations
  • 2008
  • Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A number of the deeper divergences in the placental mammal tree are still inconclusively resolved despite extensive phylogenomic analyses. A recent analysis of 200 kbp of protein coding sequences yielded only limited support for the relationships among Laurasiatheria (cow, dog, bat and shrew), probably because the divergences occurred only within a few million years from each other. It is generally expected that increasing the amount of data and improving the taxon sampling enhance the resolution of narrow divergences. Therefore these and other difficult splits were examined by phylogenomic analysis of the hitherto largest sequence alignment. The increasingly complete genome data of placental mammals also allowed developing a novel and stringent data search method. Results: The rigorous data handling, recursive BLAST, successfully removed the sequences from gene families, including those from well-known families hemoglobin, olfactory, myosin and HOX genes, thus avoiding alignment of possibly paralogous sequences. The current phylogenomic analysis of 3,012 genes (2,844,615 nucleotides) from a total of 22 species yielded statistically significant support for most relationships. While some major clades were confirmed using genomic sequence data, the placement of the treeshrew, bat and the relationship between Boreoeutheria, Xenarthra and Afrotheria remained problematic to resolve despite the size of the alignment. Phylogenomic analysis of divergence times dated the basal placental mammal splits at 95-100 million years ago. Many of the following divergences occurred only a few (2-4) million years later. Relationships with narrow divergence time intervals received unexpectedly limited support even from the phylogenomic analyses. Conclusion: The narrow temporal window within which some placental divergences took place suggests that inconsistencies and limited resolution of the mammalian tree may have their natural explanation in speciation processes such as lineage sorting, introgression from species hybridization or hybrid speciation. These processes obscure phylogenetic analysis, making some parts of the tree difficult to resolve even with genome data.
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33.
  • Hallström, Björn (författare)
  • Stroke epidemiology in Southern Sweden. Trends in incidence and survival across two decades with projections into the future
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Stroke is a major cause of death and disability. Investigations of the epidemiological trends for stroke might result in better understanding of stroke pathogenesis and prevention. Methods: The trends of first-ever stroke incidence and survival over 3 time periods (1983-85, 1993-95 and 2001/2002) in Lund-Orup health care district were studied. The first 2 study periods were retrospective and mainly hospital-based studies whereas the third study period used prospective and population-based design. The risk of dying after stroke was analyzed in a Cox proportional hazards analysis (with sex, age group, time period and stroke subtype in the analysis). A projection of the future number of strokes in Sweden was made. Results: The incidence rate (age standardized to the European Standard population per 100 000 person-years) was 134 in 1983-85 (95%CI 126-143; 998 patients), 158 in 1993-95 (95%CI 149-168; 1318 patients) and 144 in 2001/2002 (95%CI 130-158; 456 patients). The increase between the first 2 time periods was mainly confined to persons younger than 75 years (25% increase), and mainly observed for the stroke subtypes lacunar syndrome and posterior circulation syndrome. The survival within 28 days did not change significantly between the 3 study periods, but long-term survival improved between all 3 study periods. Between the first 2 periods, the survival improvement was seen only among patients aged ?75 years. The risk of dying for patients with stroke during 1993-95 was 0.85 and during 2001/2002 it was 0.67, compared with patients with stroke during 1983-85. During 2001/2002, 84% were hospitalized (within 14 days); we detected 2 main categories of patients who were not hospitalized: (1) elderly women with high 28-day case-fatality (61%), residing at nursing homes (86%), and (2) male patients with milder strokes and very good survival (0% 28-day and 1-year case-fatality). Based on official Swedish population projection and age and sex standardization from our incidence data, we project (presuming stable age-specific incidence rates) that the total annual number of first-ever strokes in Sweden might increase by no less than 55% up to year 2050. Conclusions: Stroke incidence and survival changed in our study area, which might contribute to an increase of the prevalence of stroke in the future. The importance of continuous surveillance of stroke epidemiology trends is highlighted by the projected increasing burden of stroke in our country.
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34.
  • Hallström, Björn, et al. (författare)
  • Stroke in Lund-Orup, Sweden: improved long-term survival among elderly stroke patients.
  • 2002
  • Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 33:6, s. 1624-1629
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Several studies report declining early stroke case fatality, but the findings are not consistent across geographic areas. Corresponding changes in long-term survival are less well documented. We recently reported increased stroke incidence among patients aged <75 years and stable incidence among older persons. We now report temporal trends for early and late case fatality among patients with stroke onset during 1983-1985 and 1993- 1995. METHODS: Patients living within the Lund-Orup, Sweden, hospital district and fulfilling the diagnostic criteria for first-ever stroke during 1983-1985 (n=998) and 1993-1995 (n=1318) were followed up concerning survival status at 28 days, 1 year, and 3 years. Age and sex adjustments were performed. The possible influence of Oxfordshire Community Stroke Project (OCSP) stroke subtypes on survival was also analyzed. RESULTS: Overall survival improved between the study periods (Cox proportional hazards regression: hazard ratio, 0.84; 95% confidence limits, 0.75 to 0.94; P=0.0019). The 28-day case fatality was 15% for stroke patients from both study periods. One-year case fatality was 31% for 1983-1985 patients and 27% for 1993-1995 patients. The corresponding figures at 3 years were 44% and 40%, respectively. In the group aged <75 years, there were no significant changes in overall survival, but survival improved significantly among patients aged > or = 75 years beyond 28 days after stroke onset. OCSP stroke subtype was an independent predictor of death (P<0.0001). CONCLUSIONS: The recently observed increase in stroke incidence among patients aged <75 years was not accompanied by changing survival in that age group. However, among patients aged > or =75 years, survival improved beyond 28 days after stroke. The causes of this change in survival are unknown but may be related to improved long-term care of elderly stroke patients.
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35.
  • Hallström, Björn, et al. (författare)
  • Stroke incidence and survival in the beginning of the 21st century in southern Sweden: comparisons with the late 20th century and projections into the future.
  • 2008
  • Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 39:1, s. 10-15
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: We report trends of stroke incidence and survival up to year 2001/2002 in Lund-Orup, Sweden, and projections of future stroke incidence in Sweden. METHODS: Lund Stroke Register, a prospective population-based study, included all first-ever stroke patients, between March 1, 2001 and February 28, 2002, in the Lund-Orup health care district. Institution-based studies for 1983 to 1985 and 1993 to 1995 were used for comparison. We calculated age-standardized incidence and Cox proportional hazards analysis of survival (stroke subtype, sex, age group, and study period in the analysis). Minimum follow-up was 46 months. Based on our register's stroke incidence and the official Swedish population projection, a projection for future stroke incidence on a national basis was calculated. RESULTS: We included 456 patients with first-ever stroke in 2001/2002. The age-standardized incidence (to the European population) was 144 per 100 000 person-years (95%CI 130 to 158) in 2001/2002, 158 (95%CI 149 to 168) in 1993 to 1995, and 134 (95%CI 126 to 143) in 1983 to 1985. Cox proportional hazard analysis indicated decreased risk of death after stroke in 2001/2002 (hazard ratio 0.80; 95%CI 0.67 to 0.94) compared with 1993 to 1995. Up to year 2050, the annual number of new stroke patients in Sweden may increase by 59% based solely on demographic changes. CONCLUSIONS: Despite possible underestimation of stroke incidence during the previous institution-based studies, the increased stroke incidence between 1983 to 1985 and 1993 to 1995 did not continue in 2001/2002. The long-term survival after stroke continues to improve. As the elderly population is growing in Sweden, stable incidence and increasing survival will result in a rapidly increasing prevalence of stroke patients in Sweden.
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36.
  • Hansen, N. L., et al. (författare)
  • The terpene synthase gene family in Tripterygium wilfordii harbors a labdane-type diterpene synthase among the monoterpene synthase TPS-b subfamily
  • 2017
  • Ingår i: The Plant Journal. - : Blackwell Publishing. - 0960-7412 .- 1365-313X. ; 89:3, s. 429-441
  • Tidskriftsartikel (refereegranskat)abstract
    • Tripterygium wilfordii (Celastraceae) is a medicinal plant with anti-inflammatory and immunosuppressive properties. Identification of a vast array of unusual sesquiterpenoids, diterpenoids and triterpenoids in T. wilfordii has spurred investigations of their pharmacological properties. The tri-epoxide lactone triptolide was the first of many diterpenoids identified, attracting interest due to the spectrum of bioactivities. To probe the genetic underpinning of diterpenoid diversity, an expansion of the class II diterpene synthase (diTPS) family was recently identified in a leaf transcriptome. Following detection of triptolide and simple diterpene scaffolds in the root, we sequenced and mined the root transcriptome. This allowed identification of the root-specific complement of TPSs and an expansion in the class I diTPS family. Functional characterization of the class II diTPSs established their activities in the formation of four C-20 diphosphate intermediates, precursors of both generalized and specialized metabolism and a novel scaffold for Celastraceae. Functional pairs of the class I and II enzymes resulted in formation of three scaffolds, accounting for some of the terpenoid diversity found in T. wilfordii. The absence of activity-forming abietane-type diterpenes encouraged further testing of TPSs outside the canonical class I diTPS family. TwTPS27, close relative of mono-TPSs, was found to couple with TwTPS9, converting normal-copalyl diphosphate to miltiradiene. The phylogenetic distance to established diTPSs indicates neo-functionalization of TwTPS27 into a diTPS, a function not previously observed in the TPS-b subfamily. This example of evolutionary convergence expands the functionality of TPSs in the TPS-b family and may contribute miltiradiene to the diterpenoids of T. wilfordii.
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37.
  • Huang, Mingtao, 1984, et al. (författare)
  • Efficient protein production by yeast requires global tuning of metabolism
  • 2017
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The biotech industry relies on cell factories for production of pharmaceutical proteins, of which several are among the top-selling medicines. There is, therefore, considerable interest in improving the efficiency of protein production by cell factories. Protein secretion involves numerous intracellular processes with many underlying mechanisms still remaining unclear. Here, we use RNA-seq to study the genome-wide transcriptional response to protein secretion in mutant yeast strains. We find that many cellular processes have to be attuned to support efficient protein secretion. In particular, altered energy metabolism resulting in reduced respiration and increased fermentation, as well as balancing of amino-acid biosynthesis and reduced thiamine biosynthesis seem to be particularly important. We confirm our findings by inverse engineering and physiological characterization and show that by tuning metabolism cells are able to efficiently secrete recombinant proteins. Our findings provide increased understanding of which cellular regulations and pathways are associated with efficient protein secretion.
  •  
38.
  • Huang, Mingtao, 1984, et al. (författare)
  • Microfluidic screening and whole-genome sequencing identifies mutations associated with improved protein secretion by yeast
  • 2015
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:34, s. E4689-E4696
  • Tidskriftsartikel (refereegranskat)abstract
    • There is an increasing demand for biotech-based production of recombinant proteins for use as pharmaceuticals in the food and feed industry and in industrial applications. Yeast Saccharomyces cerevisiae is among preferred cell factories for recombinant protein production, and there is increasing interest in improving its protein secretion capacity. Due to the complexity of the secretory machinery in eukaryotic cells, it is difficult to apply rational engineering for construction of improved strains. Here we used high-throughput microfluidics for the screening of yeast libraries, generated by UV mutagenesis. Several screening and sorting rounds resulted in the selection of eight yeast clones with significantly improved secretion of recombinant a-amylase. Efficient secretion was genetically stable in the selected clones. We performed whole-genome sequencing of the eight clones and identified 330 mutations in total. Gene ontology analysis of mutated genes revealed many biological processes, including some that have not been identified before in the context of protein secretion. Mutated genes identified in this study can be potentially used for reverse metabolic engineering, with the objective to construct efficient cell factories for protein secretion. The combined use of microfluidics screening and whole-genome sequencing to map the mutations associated with the improved phenotype can easily be adapted for other products and cell types to identify novel engineering targets, and this approach could broadly facilitate design of novel cell factories.
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39.
  • Jansson, Magnus, 1962- (författare)
  • Vardagliga teknikaktiviteter i fritidshem : organisation, didaktik och görande
  • 2023
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Det övergripande syftet med denna licentiatstudie är att undersöka hur teknik som undervisningsområde kommer till uttryck inom fritidsverksamheter. Syftet inrymmer ett fokus på vad fritidslärarna gör för att organisera undervisning. Studien utgår ifrån följande frågeställningar: hur ser fritidslärarna på undervisning i teknik i fritidshem; och hur organiseras teknik som en del av undervisnings-praktiken i fritidshem? Studien är kvalitativ samt inspirerad av etnografi och Grounded theory. Studiens teoretiska perspektiv är symbolisk interaktionism, samt Mitchams modell för manifestation av teknik från 1994. Studien är en fält-studie på tre olika fritidshem. I studiens bakgrundsbeskrivning påvisas att fritidshem har haft en historia där hantverk och olika estetiska aktiviteter varit vanligt förekommande aktiviteter. Fritidshemmen har också, i och med en tydligare styrning kring lärandet, fått del i läroplanen Lgr11 (reviderad 2016), där tekniken är en framskriven del av undervisningen. Studien handlar därför om hur fritidshemspersonalen reflekterar och förhandlar och definierar för att göra olika teknikaktiviteter. Fritidshemspersonalen gör, enligt studien, här en nyorientering för att tolka innehållet i den egna läroplansdelen. I denna nyorientering använder fritidshemspersonalen sig av tre olika strategier för att hantera detta med teknik som undervisning, detta i ett gränsland mellan tidigare idétraditioner och en utökad styrning.
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40.
  • Jarmander, Johan, et al. (författare)
  • Simultaneous Uptake of Lignocellulose- Based Monosaccharides by Escherichia Coli
  • 2014
  • Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 111:6, s. 1108-1115
  • Tidskriftsartikel (refereegranskat)abstract
    • Lignocellulosic waste is a naturally abundant biomass and is therefore an attractive material to use in second generation biorefineries. Microbial growth on the monosaccharides present in hydrolyzed lignocellulose is however associated with several obstacles whereof one is the lack of simultaneous uptake of the sugars. We have studied the aerobic growth of Escherichia coli on D-glucose, D-xylose, and L-arabinose and for simultaneous uptake to occur, both the carbon catabolite repression mechanism (CCR) and the AraC repression of xylose uptake and metabolism had to be removed. The strain AF1000 is a MC4100 derivative that is only able to assimilate arabinose after a considerable lag phase, which is unsuitable for commercial production. This strain was successfully adapted to growth on L-arabinose and this led to simultaneous uptake of arabinose and xylose in a diauxic growth mode following glucose consumption. In this strain, a deletion in the phosphoenolpyruvate:phosphotransferase system (PTS) for glucose uptake, the ptsG mutation, was introduced. The resulting strain, PPA652ara simultaneously consumed all three monosaccharides at a maximum specific growth rate of 0.59h(-1), 55% higher than for the ptsG mutant alone. Also, no residual sugar was present in the cultivation medium. The potential of PPA652ara is further acknowledged by the performance of AF1000 during fed-batch processing on a mixture of D-glucose, D-xylose, and L-arabinose. The conclusion is that without the removal of both layers of carbon uptake control, this process results in accumulation of pentoses and leads to a reduction of the specific growth rate by 30%.
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41.
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42.
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43.
  • Jönsson, Ann-Cathrin, et al. (författare)
  • Prevalence and intensity of pain after stroke: a population based study focusing on patients' perspectives.
  • 2005
  • Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - 1468-330X. ; , s. 590-595
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine prevalence and intensity of pain after stroke, focusing on patients' perspectives. METHODS: During a one year period, 416 first-ever stroke patients were included in the population based Lund Stroke Register. After 4 and 16 months (median), 297 patients (98% of survivors) were followed up. Worst pain intensity during the previous 48 hours was assessed on a visual analogue scale (VAS), range 0 to 100: a score of 0 to 30 was defined as no or mild pain; 40 to 100 as moderate to severe pain. NIH stroke scale (NIHSS) score and HbA1c were assessed at baseline. At 16 months, screening for depression was done using the geriatric depression scale (GDS-20), and cognition with the mini-mental state examination (MMSE). Predictors of pain were determined by multivariate analyses. RESULTS: Moderate to severe pain was reported by 96 patients (32%) after four months (VAS median=60). Predictors of pain were younger age (p=0.01), female sex (p=0.006), higher NIHSS score (p<0.001), and raised HbA1c (p=0.001) at stroke onset. At 16 months, only 62 patients (21%) had moderate to severe pain, but pain intensity was more severe (median VAS score=70; p<0.016). Higher pain intensity correlated with female sex, worse GDS-20 score, better MMSE score, and raised HbA1c. Pain was persistent in 47%, disturbed sleep in 58%, and required rest for relief in 40% of patients. CONCLUSIONS: Although prevalence of pain after stroke decreased with time, after 16 months 21% had moderate to severe pain. Late pain after stroke was on average more severe, and profoundly affected the patients' wellbeing.
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44.
  • Kampf, Caroline, et al. (författare)
  • Defining the human gallbladder proteome by transcriptomics and affinity proteomics
  • 2014
  • Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 14:21-22, s. 2498-2507
  • Tidskriftsartikel (refereegranskat)abstract
    • Global protein analysis of human gallbladder tissue is vital for identification of molecular regulators and effectors of its physiological activity. Here, we employed a genome-wide deep RNA sequencing analysis in 28 human tissues to identify the genes overrepresented in the gallbladder and complemented it with antibody-based immunohistochemistry in 48 human tissues. We characterized human gallbladder proteins and identified 140 gallbladder-specific proteins with an elevated expression in the gallbladder as compared to the other analyzed tissues. Five genes were categorized as enriched, with at least fivefold higher levels in gallbladder, 60 genes were categorized as group enriched with elevated transcript levels in gallbladder shared with at least one other tissue and 75 genes were categorized as enhanced with higher expression than the average expression in other tissues. We explored the localization of the genes within the gallbladder through cell-type specific antibody-based protein profiling and the subcellular localization of the genes through immunofluorescent-based profiling. Finally, we revealed the biological processes and metabolic functions carried out by these genes through the use of GO, KEGG Pathway, and HMR2.0 that is compilation of the human metabolic reactions. We demonstrated the results of the combined analysis of the transcriptomics and affinity proteomics.
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45.
  • Kampf, Caroline, et al. (författare)
  • The human liver-specific proteome defined by transcriptomics and antibody-based profiling
  • 2014
  • Ingår i: FASEB Journal. - : Wiley. - 1530-6860 .- 0892-6638. ; 28:7, s. 2901-2914
  • Tidskriftsartikel (refereegranskat)abstract
    • Human liver physiology and the genetic etiology of the liver diseases can potentially be elucidated through the identification of proteins with enriched expression in the liver. Here, we combined data from RNA sequencing (RNA-Seq) and antibody-based immunohistochemistry across all major human tissues to explore the human liver proteome with enriched expression, as well as the cell type-enriched expression in hepatocyte and bile duct cells. We identified in total 477 protein-coding genes with elevated expression in the liver: 179 genes have higher expression as compared to all the other analyzed tissues; 164 genes have elevated transcript levels in the liver shared with at least one other tissue type; and an additional 134 genes have a mild level of increased expression in the liver. We identified the precise localization of these proteins through antibody-based protein profiling and the subcellular localization of these proteins through immunofluorescent-based profiling. We also identified the biological processes and metabolic functions associated with these proteins, investigated their contribution in the occurrence of liver diseases, and identified potential targets for their treatment. Our study demonstrates the use of RNA-Seq and antibody-based immunohistochemistry for characterizing the human liver proteome, as well as the use of tissue-specific proteins in identification of novel drug targets and discovery of biomarkers.
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46.
  • Kapur, Rick, et al. (författare)
  • Gastrointestinal microbiota contributes to the development of murine transfusion-related acute lung injury
  • 2018
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:13, s. 1651-1663
  • Tidskriftsartikel (refereegranskat)abstract
    • Transfusion-related acute lung injury (TRALI) is a syndrome of respiratory distress upon blood transfusion and is the leading cause of transfusion-related fatalities. Whether the gut microbiota plays any role in the development of TRALI is currently unknown. We observed that untreated barrier-free (BF) mice suffered from severe antibody-mediated acute lung injury, whereas the more sterile housed specific pathogen-free (SPF) mice and gut flora-depleted BF mice were both protected from lung injury. The prevention of TRALI in the SPF mice and gut flora-depleted BF mice was associated with decreased plasma macrophage inflammatory protein-2 levels as well as decreased pulmonary neutrophil accumulation. DNA sequencing of amplicons of the 16S ribosomal RNA gene revealed a varying gastrointestinal bacterial composition between BF and SPF mice. BF fecal matter transferred into SPF mice significantly restored TRALI susceptibility in SPF mice. These data reveal a link between the gut flora composition and the development of antibody-mediated TRALI in mice. Assessment of gut microbial composition may help in TRALI risk assessment before transfusion.
  •  
47.
  • Kildegaard, Kanchana R., et al. (författare)
  • Evolution reveals a glutathione-dependent mechanism of 3-hydroxypropionic acid tolerance
  • 2014
  • Ingår i: Metabolic engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 26, s. 57-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Biologically produced 3-hydroxypropionic acid (3HP) is a potential source for sustainable acrylates and can also find direct use as monomer in the production of biodegradable polymers. For industrial scale production there is a need for robust cell factories tolerant to high concentration of 3HP, preferably at low pH. Through adaptive laboratory evolution we selected S. cerevisiae strains with improved tolerance to 3HP at pH 3.5. Genome sequencing followed by functional analysis identified the causal mutation in SFA1 gene encoding S-(hyclroxymerhyl)glutathione dehydrogenase. Based on our findings, we propose that 3HP toxicity is mediated by 3-hydroxypropionic aldehyde (reuterin ) and that glutathione-dependent reactions are used for reuterin detoxification. The identified molecular response to 3HP and reuterin may well be a general mechanism for handling resistance to organic acid and aldehydes by living cells. (C) 2014 International Metabolic Engineering Society Published by Elsevier Inc. On behalf of International Metabolic Engineering Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/)
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48.
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49.
  • Kristensson Hallström, Inger, et al. (författare)
  • eHealth as an Aid for Facilitating and Supporting Self-Management in Families with Long-Term Childhood Illness; Development, Evaluation, and Implementation in Clinical Practice
  • 2023
  • Ingår i: Clinical Health Promotion - Research and Best Practice for patients, staff and community. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction eHealth, defined by WHO as: “the transfer of health resources and healthcare by electronic means” are expected to increase communication between healthcare providers and patients and increase accessibility and patient participation in healthcare. The aim of this research programme is to: 1) develop a sustainable multidisciplinary environment for advancing, evaluating, and implementing models of eHealth to promote self-management for children and their families, and 2) increase the present knowledge of clinical and economic cost-effectiveness of eHealth as an aid for supporting self-management in families with long-term childhood illness. Method The research is performed in Sweden, Denmark, and Ethiopia and organized in three research domains: eHealth to enable and promote self-management in advanced paediatric care, eHealth for early diagnosis and treatment in paediatric care, and Co-Creation of multidisciplinary knowledge for the translation of eHealth in practice. The research follows a framework for developing and evaluating complex interventions in healthcare. Through participatory design family members and care providers participate throughout the research process. Quantitative and qualitative data as well as health economics are collected in six clinical areas. Five general areas are run transversal. Results and conclusion Evidence-based best practices in developing and evaluating eHealth in paediatric healthcare will be suggested. As implementation is part of the programme, cost-effective eHealth directly benefiting families and healthcare services will be guaranteed.
  •  
50.
  • Kullberg, Morgan, et al. (författare)
  • Expressed sequence tags as a tool for phylogenetic analysis of placental mammal evolution.
  • 2007
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 2:8, s. 775-775
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We investigate the usefulness of expressed sequence tags, ESTs, for establishing divergences within the tree of placental mammals. This is done on the example of the established relationships among primates (human), lagomorphs (rabbit), rodents (rat and mouse), artiodactyls (cow), carnivorans (dog) and proboscideans (elephant). METHODOLOGY/PRINCIPAL FINDINGS: We have produced 2000 ESTs (1.2 mega bases) from a marsupial mouse and characterized the data for their use in phylogenetic analysis. The sequences were used to identify putative orthologous sequences from whole genome projects. Although most ESTs stem from single sequence reads, the frequency of potential sequencing errors was found to be lower than allelic variation. Most of the sequences represented slowly evolving housekeeping-type genes, with an average amino acid distance of 6.6% between human and mouse. Positive Darwinian selection was identified at only a few single sites. Phylogenetic analyses of the EST data yielded trees that were consistent with those established from whole genome projects. CONCLUSIONS: The general quality of EST sequences and the general absence of positive selection in these sequences make ESTs an attractive tool for phylogenetic analysis. The EST approach allows, at reasonable costs, a fast extension of data sampling from species outside the genome projects.
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