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Sökning: WFRF:(Lindblad Peter)

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1.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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2.
  • Lindblad-Toh, Kerstin, et al. (författare)
  • Genome sequence, comparative analysis and haplotype structure of the domestic dog.
  • 2005
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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3.
  • Clark, Andrew G., et al. (författare)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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4.
  • Hess, Timo, et al. (författare)
  • Dissecting the genetic heterogeneity of gastric cancer
  • 2023
  • Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. 
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5.
  • Braasch, Ingo, et al. (författare)
  • The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:4, s. 427-437
  • Tidskriftsartikel (refereegranskat)abstract
    • To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.
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6.
  • Amemiya, Chris T., et al. (författare)
  • The African coelacanth genome provides insights into tetrapod evolution
  • 2013
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 496:7445, s. 311-316
  • Tidskriftsartikel (refereegranskat)abstract
    • The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
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7.
  • Berglund, Lisa, et al. (författare)
  • Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.
  • 2016
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 65:1, s. 239-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a "vascular disease-like" phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients.
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8.
  • Bericat Vadell, Robert, et al. (författare)
  • Single-electron transfer reactions on surface-modified gold plasmons
  • 2023
  • Ingår i: Materials Today Chemistry. - : Elsevier. - 2468-5194. ; 34
  • Tidskriftsartikel (refereegranskat)abstract
    • Photoredox catalysis's relevance in organic synthesis research and innovation will increase in the coming decades. However, the processes rely almost exclusively on expensive noble metal complexes, most notably iridium complexes, to absorb light and transfer a single charge to a substrate or a catalyst to initiate cascade transformations. Light-triggered plasmon resonances generate a non-Fermi-Dirac energy distribution with many hot carriers that decay in similar to 1 ps. Their ultrafast relaxation makes performing single electron transfer (SET) transformations challenging. Herein, a novel photosystem is proposed based on surface-modified gold nanoparticles (aka plasmon "molecularization"), which improved charge separation and, more importantly, enabled SET reactions, expanding the portfolio of photocatalysts available for photoredox catalysis. The photosystem was made into an electrode, permitting its use in photoelectrochemical arrangements that leverage electro- and photo-chemical approaches' benefits and chemical engineering solutions, helping the synthetic chemistry efforts towards greener synthesis and synthesis of more complex structures on a scale.
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9.
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10.
  • Camsund, Daniel, et al. (författare)
  • A HupS-GFP fusion protein demonstrates a heterocyst-specific localization of the uptake hydrogenase in Nostoc punctiforme
  • 2011
  • Ingår i: FEMS Microbiology Letters. - : John Wiley & Sons. - 0378-1097 .- 1574-6968. ; 316:2, s. 152-159
  • Tidskriftsartikel (refereegranskat)abstract
    • All diazotrophic filamentous cyanobacteria contain an uptake hydrogenase that is involved in the reoxidation of H-2 produced during N-2-fixation. In Nostoc punctiforme ATCC 29133, N-2-fixation takes place in the microaerobic heterocysts, catalysed by a nitrogenase. Although the function of the uptake hydrogenase may be closely connected to that of nitrogenase, the localization in cyanobacteria has been under debate. Moreover, the subcellular localization is not understood. To investigate the cellular and subcellular localization of the uptake hydrogenase in N. punctiforme, a reporter construct consisting of the green fluorescent protein (GFP) translationally fused to HupS, within the complete hupSL operon, was constructed and transferred into N. punctiforme on a self-replicative vector by electroporation. Expression of the complete HupS-GFP fusion protein was confirmed by Western blotting using GFP antibodies. The N. punctiforme culture expressing HupS-GFP was examined using laser scanning confocal microscopy, and fluorescence was exclusively detected in the heterocysts. Furthermore, the fluorescence in mature heterocysts was localized to several small or fewer large clusters, which indicates a specificity of the subcellular localization of the uptake hydrogenase.
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11.
  • Larson, Greger, et al. (författare)
  • Rethinking dog domestication by integrating genetics, archeology, and biogeography
  • 2012
  • 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. ; 109, s. 8878-8883
  • Tidskriftsartikel (refereegranskat)abstract
    • The dog was the first domesticated animal but it remains uncertain when the domestication process began and whether it occurred just once or multiple times across the Northern Hemisphere. To ascertain the value of modern genetic data to elucidate the origins of dog domestication, we analyzed 49,024 autosomal SNPs in 1,375 dogs (representing 35 breeds) and 19 wolves. After combining our data with previously published data, we contrasted the genetic signatures of 121 breeds with a worldwide archeological assessment of the earliest dog remains. Correlating the earliest archeological dogs with the geographic locations of 14 so-called "ancient" breeds (defined by their genetic differentiation) resulted in a counterintuitive pattern. First, none of the ancient breeds derive from regions where the oldest archeological remains have been found. Second, three of the ancient breeds (Basenjis, Dingoes, and New Guinea Singing Dogs) come from regions outside the natural range of Canis lupus (the dog's wild ancestor) and where dogs were introduced more than 10,000 y after domestication. These results demonstrate that the unifying characteristic among all genetically distinct so-called ancient breeds is a lack of recent admixture with other breeds likely facilitated by geographic and cultural isolation. Furthermore, these genetically distinct ancient breeds only appear so because of their relative isolation, suggesting that studies of modern breeds have yet to shed light on dog origins. We conclude by assessing the limitations of past studies and how next-generation sequencing of modern and ancient individuals may unravel the history of dog domestication.
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12.
  • Lindblad, Caroline, et al. (författare)
  • Fluid proteomics of CSF and serum reveal important neuroinflammatory proteins in blood-brain barrier disruption and outcome prediction following severe traumatic brain injury : a prospective, observational study
  • 2021
  • Ingår i: Critical Care. - : Springer Nature. - 1364-8535 .- 1466-609X. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Severe traumatic brain injury (TBI) is associated with blood-brain barrier (BBB) disruption and a subsequent neuroinflammatory process. We aimed to perform a multiplex screening of brain enriched and inflammatory proteins in blood and cerebrospinal fluid (CSF) in order to study their role in BBB disruption, neuroinflammation and long-term functional outcome in TBI patients and healthy controls. Methods: We conducted a prospective, observational study on 90 severe TBI patients and 15 control subjects. Clinical outcome data, Glasgow Outcome Score, was collected after 6-12 months. We utilized a suspension bead antibody array analyzed on a FlexMap 3D Luminex platform to characterize 177 unique proteins in matched CSF and serum samples. In addition, we assessed BBB disruption using the CSF-serum albumin quotient (Q(A)), and performed Apolipoprotein E-genotyping as the latter has been linked to BBB function in the absence of trauma. We employed pathway-, cluster-, and proportional odds regression analyses. Key findings were validated in blood samples from an independent TBI cohort. Results: TBI patients had an upregulation of structural CNS and neuroinflammatory pathways in both CSF and serum. In total, 114 proteins correlated with Q(A), among which the top-correlated proteins were complement proteins. A cluster analysis revealed protein levels to be strongly associated with BBB integrity, but not carriage of the Apolipoprotein E4-variant. Among cluster-derived proteins, innate immune pathways were upregulated. Forty unique proteins emanated as novel independent predictors of clinical outcome, that individually explained similar to 10% additional model variance. Among proteins significantly different between TBI patients with intact or disrupted BBB, complement C9 in CSF (p = 0.014, Delta R-2 = 7.4%) and complement factor B in serum (p = 0.003, Delta R-2 = 9.2%) were independent outcome predictors also following step-down modelling. Conclusions: This represents the largest concomitant CSF and serum proteomic profiling study so far reported in TBI, providing substantial support to the notion that neuroinflammatory markers, including complement activation, predicts BBB disruption and long-term outcome. Individual proteins identified here could potentially serve to refine current biomarker modelling or represent novel treatment targets in severe TBI.
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13.
  • Meadows, Jennifer, et al. (författare)
  • Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture
  • 2023
  • Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 24
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The international Dog10K project aims to sequence and analyze several thousand canine genomes. Incorporating 20 x data from 1987 individuals, including 1611 dogs (321 breeds), 309 village dogs, 63 wolves, and four coyotes, we identify genomic variation across the canid family, setting the stage for detailed studies of domestication, behavior, morphology, disease susceptibility, and genome architecture and function.Results: We report the analysis of > 48 M single-nucleotide, indel, and structural variants spanning the autosomes, X chromosome, and mitochondria. We discover more than 75% of variation for 239 sampled breeds. Allele sharing analysis indicates that 94.9% of breeds form monophyletic clusters and 25 major clades. German Shepherd Dogs and related breeds show the highest allele sharing with independent breeds from multiple clades. On average, each breed dog differs from the UU_Cfam_GSD_1.0 reference at 26,960 deletions and 14,034 insertions greater than 50 bp, with wolves having 14% more variants. Discovered variants include retrogene insertions from 926 parent genes. To aid functional prioritization, single-nucleotide variants were annotated with SnpEff and Zoonomia phyloP constraint scores. Constrained positions were negatively correlated with allele frequency. Finally, the utility of the Dog10K data as an imputation reference panel is assessed, generating high-confidence calls across varied genotyping platform densities including for breeds not included in the Dog10K collection.Conclusions: We have developed a dense dataset of 1987 sequenced canids that reveals patterns of allele sharing, identifies likely functional variants, informs breed structure, and enables accurate imputation. Dog10K data are publicly available.
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14.
  • Miranda, Hélder, et al. (författare)
  • Sll1783, a monooxygenase associated with polysaccharide processing in the unicellular cyanobacterium Synechocystis PCC 6803
  • 2017
  • Ingår i: Physiologia Plantarum. - : Wiley. - 0031-9317 .- 1399-3054. ; 161:2, s. 182-195
  • Tidskriftsartikel (refereegranskat)abstract
    • Cyanobacteria play a pivotal role as the primary producer in many aquatic ecosystems. The knowledge on the interacting processes of cyanobacteria with its environment - abiotic and biotic factors - is still very limited. Many potential exocytoplasmic proteins in the model unicellular cyanobacterium Synechocystis PCC 6803 have unknown functions and their study is essential to improve our understanding of this photosynthetic organism and its potential for biotechnology use. Here we characterize a deletion mutant of Synechocystis PCC 6803, Δsll1783, a strain that showed a remarkably high light resistance which is related with its lower thylakoid membrane formation. Our results suggests Sll1783 to be involved in a mechanism of polysaccharide degradation and uptake and we hypothesize it might function as a sensor for cell density in cyanobacterial cultures.
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15.
  • Saxena, Richa, et al. (författare)
  • Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
  • 2007
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
  • Tidskriftsartikel (refereegranskat)abstract
    • New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
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16.
  • Villamayor, Michelle Marie S., et al. (författare)
  • Wafer-sized WS2 monolayer deposition by sputtering
  • 2022
  • Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 14:17, s. 6331-6338
  • Tidskriftsartikel (refereegranskat)abstract
    • We demonstrate that tungsten disulphide (WS2) with thicknesses ranging from monolayer (ML) to several monolayers can be grown on SiO2/Si, Si, and Al2O3 by pulsed direct current-sputtering. The presence of high quality monolayer and multilayered WS2 on the substrates is confirmed by Raman spectroscopy since the peak separations between the A(1g)-E-2g and A(1g)-2LA vibration modes exhibit a gradual increase depending on the number of layers. X-ray diffraction confirms a textured (001) growth of WS2 films. The surface roughness measured with atomic force microscopy is between 1.5 and 3 angstrom for the ML films. The chemical composition WSx (x = 2.03 +/- 0.05) was determined from X-ray Photoelectron Spectroscopy. Transmission electron microscopy was performed on a multilayer film to show the 2D layered structure. A unique method for growing 2D layers directly by sputtering opens up the way for designing 2D materials and batch production of high-uniformity and high-quality (stochiometric, large grain sizes, flatness) WS2 films, which will advance their practical applications in various fields.
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17.
  • Abrahamsson, Anna, et al. (författare)
  • Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma Group observational study.
  • 2014
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:8, s. 1288-1295
  • Tidskriftsartikel (refereegranskat)abstract
    • There is consensus that young patients with mantle cell lymphoma (MCL) should receive intensive immunochemotherapy regimens, but optimal treatment of elderly patients as well for as patients with limited or indolent disease is not defined. Our aim was to evaluate and compare outcome in relation to prognostic factors and first-line treatment in patients with MCL in a population-based data set. Data were collected from the Swedish and Danish Lymphoma Registries from the period of 2000-2011. A total of 1389 patients were diagnosed with MCL. During this period, age-standardized incidence MCL increased, most prominently among males. Furthermore, male gender was associated with inferior overall survival (OS) in multivariate analysis (HR 1.36; p=0.002). Forty-three (3.6%) patients with stage I-II disease received radiotherapy with curative intent, showing a 3 year OS of 93%. Twenty-nine (2.4%) patients followed a watch-and-wait approach and showed a 3 year OS of 79.8%. Among patients receiving systemic treatment, rituximab (n=766; HR 0.66; p=0.001) and autologous stem cell transplant (ASCT) (n=273; HR 0.55; p=0.004) were independently associated with improved overall survival in multivariate analysis. Hence, by a population-based approach, we were able to provide novel data on prognostic factors and primary treatment of MCL, applicable to routine clinical practice.
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18.
  • Adolfsson, Peter, 1963, et al. (författare)
  • Continuous glucose monitoring system during physical exercise in adolescents with type 1 diabetes
  • 2011
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 100:12, s. 1603-1609
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Continuous glucose monitoring system (CGMS) provides detailed information on glucose fluctuations. The aim was to establish whether CGMS could be used during physical exercise and whether it detects more episodes of hypoglycaemia and hyperglycaemia than frequent blood glucose measurements. Methods: Adolescents with type 1 diabetes (12 girls and 47 boys) participated in three annual sports camps that lasted for 3-4 days and included different types of exercise: soccer, floorball + cross-country skiing and golf. During the study, blood glucose values, mean 8.7 +/- 3.3 per day, were obtained with Hemocue in parallel with the CGMS. Results: Ninety-eight per cent of the participants used the sensor at all times during the camps. Eighty-seven per cent of the sensors gave adequate signals for 24 h and 66% for 48 h. Median durations of hypoglycaemia and hyperglycaemia were 1.7 h per day and 3.8 h per day, respectively. The CGMS identified significantly more episodes of hypoglycaemia (p < 0.005) and hyperglycaemia (p < 0.005) during the day and night than frequent blood glucose tests. Conclusion: We demonstrate that, even during days that included episodic strenuous physical exercise, CGMS could provide useful information on glucose fluctuations during day and night, albeit with significant failure rates.
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19.
  • Adolfsson, Peter, 1963, et al. (författare)
  • Hormonal response during physical exercise of different intensities in adolescents with type 1 diabetes and healthy controls.
  • 2012
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 13:8, s. 587-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Physical activity is a critical component in the care of diabetes. Although it offers health benefits it presents challenges. Objective To investigate differences between adolescent boys and girls with type 1 diabetes and healthy controls in terms of maximal work capacity (VO2 max) and hormonal response to physical exercise of different intensities. Subjects Twelve individuals (six boys and six girls; age 1419 yr, pubertal stage 45) with type 1 diabetes (duration, 6.3 +/- 4.4 yr; hemoglobin A1c, 63 +/- 10 mmol/mol) were compared with 12 healthy controls matched for age, sex, pubertal stage, body mass index standard deviation score, and amount of regular physical activity. Methods During consecutive days, three different workloads; maximal, endurance, and interval, were performed on an Ergometer cycle. During the tests, levels of lactate, glucose, insulin, and regulatory hormones [glucagon, cortisol, growth hormone (GH), adrenaline, and noradrenaline] were measured in blood. Subcutaneous glucose was measured continuously. Results VO2 max did not differ between the groups, diabetes 49.8 +/- 9.9 vs. control 50.7 +/- 12.0 mL/min/kg. Hormonal responses did not differ between the groups except for mean peak GH level during the interval test, diabetes 63.2 +/- 27.0 vs. control 33.8 +/- 20.9 mU/L, p
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20.
  • af Klint, Erik, et al. (författare)
  • Evaluation of arthroscopy and macroscopic scoring.
  • 2009
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Arthroscopy is a minimally invasive technique for retrieving synovial biopsies in rheumatology during the past 20 years. Vital for its use is continual evaluation of its safety and efficacy. Important for sampling is the fact of intraarticular variation for synovial markers. For microscopic measurements scoring systems have been developed and validated, but for macroscopic evaluations there is a need for further comprehensive description and validation of equivalent scoring systems.METHODS: We studied the complication rate and yield of arthroscopies performed at our clinic between 1998 and 2005. We also created and evaluated a macroscopic score set of instructions for synovitis.RESULTS: Of 408 procedures, we had two major and one minor complication; two haemarthrosis and one wound infection, respectively. Pain was most often not a problem, but 12 procedures had to be prematurely ended due to pain. Yield of biopsies adequate for histology were 83% over all, 94% for knee joints and 34% for smaller joints. Video printer photographs of synovium taken during arthroscopy were jointly and individually reviewed by seven raters in several settings, and intra and inter rater variation was calculated. A macroscopic synovial scoring system for arthroscopy was created (Macro-score), based upon hypertrophy, vascularity and global synovitis. These written instructions were evaluated by five control-raters, and when evaluated individual parameters were without greater intra or inter rater variability, indicating that the score is reliable and easy to use.CONCLUSIONS: In our hands rheumatologic arthroscopy is a safe method with very few complications. For knee joints it is a reliable method to retrieve representative tissue in clinical longitudinal studies. We also created an easy to use macroscopic score, that needs to be validated against other methodologies. We hope it will be of value in further developing international standards in this area.
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21.
  • Agervald, Åsa, et al. (författare)
  • CalA, a cyanobacterial AbrB protein, interacts with the upstream region of hypC and acts as a repressor of its transcription in the cyanobacterium Nostoc sp. strain PCC 7120
  • 2010
  • Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 76:3, s. 880-890
  • Tidskriftsartikel (refereegranskat)abstract
    • The filamentous, heterocystous, nitrogen-fixing cyanobacterium Nostoc sp. strain PCC 7120 may contain, depending on growth condition, up to two hydrogenases directly involved in hydrogen metabolism. HypC is one out of at least seven auxiliary gene products required for synthesis of a functional hydrogenase, specifically involved in the maturation of the large subunit. In this study we present a protein, Alr0946, belonging to the transcription regulator family AbrB, which in protein-DNA assays was found to interact with the upstream region of hypC. Transcriptional investigations showed that alr0946 is co-transcribed with the downstream gene alr0947, which encodes a putative protease from the abortive infection superfamily, Abi. Alr0946 was shown to interact specifically not only with the upstream region of hypC but also with its own upstream region, acting as a repressor on both. The bidirectional hydrogenase activity was significant down-regulated when Alr0946 was over-expressed demonstrating a correlation to the transcription factor, either direct or indirect. In silico studies showed that homologues to both Alr0946 and Alr0947 are highly conserved proteins within cyanobacteria with a very similar physical organisation of the corresponding structural genes. Possible functions of the co-transcribed downstream protein Alr0947 are presented. In addition, we present a 3D model of the CyAbrB domain of Alr0946 and putative DNA-binding mechanisms are discussed.
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22.
  • Agervald, Åsa, et al. (författare)
  • CRISPR in the extended hyp-operon of the cyanobacterium Nostoc sp. strain PCC 7120, characteristics and putative function(s)
  • 2012
  • Ingår i: International journal of hydrogen energy. - : Elsevier BV. - 0360-3199 .- 1879-3487. ; 37:10, s. 8828-8833
  • Tidskriftsartikel (refereegranskat)abstract
    • The presence of small RNAs (sRNA) and their functions in transcriptional regulation has lately turned into a hot topic. Since cyanobacteria often face changes in the surrounding environment, they need to have a well working system for stress response. Quick adaption is necessary, and an RNA-based regulatory system is thus useful. One example of these sRNAs is CRISPRs. In this work we report the existence of a CRISPR within the hyp-operon (hyp genes encode proteins responsible for the maturation of hydrogenases) of the filamentous cyanobacterium Nostoc sp. strain PCC 7120. We present data concerning its characteristics and putative function(s) and raise the question concerning the importance of this CRISPR array and other CRISPR systems in general. In addition, we discuss the use of the CRISPR system as a potential bacterial genetic defence mechanism to achieve robust, cyanobacterial cultures in large scale, commercial production units.
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23.
  • Agervald, Åsa (författare)
  • Maturation and Regulation of Cyanobacterial Hydrogenases
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Accelerated global warming plus an increasing need for energy is an equation not easily solved, thus new forms of sustainable energy production are urgently requested. In this context hydrogen production based on a cyanobacterial system offers an environmentally friendly alternative for energy capture and conversion. Cyanobacteria can produce hydrogen gas from sun light and water through the combination of photosystems and hydrogenases, and are suitable to cultivate in large scale. In the present thesis the maturation process of [NiFe]-hydrogenases is investigated with special focus on transcription of the accessory genes encoding proteins needed for assembly of the large and possibly also for the small hydrogenase subunit. The cyanobacteria used are two N2-fixing, filamentous, heterocystous strains; Nostoc sp. strain PCC 7120 and Nostoc punctiforme PCC 73102. For a biotechnological exploration of hydrogen production tools for regulatory purposes are important. The transcription factor CalA (cyanobacterial AbrB like) (Alr0946 in the genome) in Nostoc sp. strain PCC 7120 was found to be involved in hydrogen metabolism by regulating the transcription of the maturation protein HypC. Further the bidirectional hydrogenase activity was down-regulated in the presence of elevated levels of CalA, a result important to take into account when optimizing cyanobacteria for hydrogen production. CalA regulates at least 25 proteins in Nostoc sp. strain PCC 7120 and one of the down-regulated proteins was superoxide dismutase, FeSOD. The characterization of FeSOD shows that it has a specific and important function in the oxidative stress tolerance of Nostoc sp. stain PCC 7120. Since CalA is involved in regulation of both the hydrogen metabolism as well as stress responses these findings indicate that Alr0946 is an important transcription factor in Nostoc sp. strain PCC 7120 active on a global level in the cell. This thesis adds more knowledge concerning maturation and regulation of cyanobacterial hydrogenases which might be useful for future large scale hydrogen.
  •  
24.
  • Agervald, Åsa, et al. (författare)
  • The CyAbrB transcription factor Alr0946 regulates the iron superoxide dismutase in Nostoc sp. strain PCC 7120
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • In the present investigation we analyse the results of induced over-production of the CyAbrB transcription factor Alr0946 in the cyanobacterium Nostoc sp. PCC 7120 with special focus on its effects on FeSOD. With gel based quantitative proteomics the induced over-expression of Alr0946 was shown to influence the abundance of at least 25 proteins. One of the proteins with a significant lower abundance was FeSOD, one of two types of superoxide dismutases in Nostoc sp. PCC 7120. The change in protein abundance was also followed by lower transcript as well as activity levels. Purified Alr0946 from Nostoc sp. PCC 7120 was shown to interact with the promoter region of alr2938, encoding FeSOD, indicating a transcriptional regulation of FeSOD by Alr0946. The Alr0946 over-expression strain showed a bleaching phenotype with lower growth rate and truncated filaments already two days after induction of over-expression. The phenotype was even more pronounced when illumination was increased from 35 to 125 μmol m-2s-1. This is in line with an increased need of FeSOD during a stronger oxidative stress. The results indicate that Alr0946 is involved in regulation of stress responses and that FeSOD has a specific and important function in the oxidative stress tolerance of the multicellular cyanobacterium Nostoc sp. PCC 7120.
  •  
25.
  • Agervald, Åsa, et al. (författare)
  • The CyAbrB transcription factor CalA regulates the iron superoxide dismutase in Nostoc sp. strain PCC 7120
  • 2010
  • Ingår i: Environmental Microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 12:10, s. 2826-2837
  • Tidskriftsartikel (refereegranskat)abstract
    • P>In the present investigation the results of induced over-production of the CyAbrB transcription factor CalA (Cyanobacterial AbrB-like, annotated as Alr0946) in the cyanobacterium Nostoc sp. PCC 7120 were analysed. The CalA overexpression strain showed a bleaching phenotype with lower growth rate and truncated filaments 2 days after induction of overexpression. The phenotype was even more pronounced when illumination was increased from 35 to 125 mu mol m-2 s-1. Using gel-based quantitative proteomics, the induced overexpression of CalA was shown to downregulate the abundance of FeSOD, one of two types of superoxide dismutases in Nostoc sp. PCC 7120. The change in protein abundance was also accompanied by lower transcript as well as activity levels. Purified recombinant CalA from Nostoc sp. PCC 7120 was shown to interact with the promoter region of alr2938, encoding FeSOD, indicating a transcriptional regulation of FeSOD by CalA. The bleaching phenotype is in line with a decreased tolerance against oxidative stress and indicates that CalA is involved in regulation of cellular responses in which FeSOD has an important and specific function in the filamentous cyanobacterium Nostoc sp. PCC 7120.
  •  
26.
  • Agervald, Åsa, et al. (författare)
  • Transcription of the extended hyp-operon in Nostoc sp. strain PCC 7120
  • 2008
  • Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 8, s. 69-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The maturation of hydrogenases into active enzymes is a complex process and e. g. a correctly assembled active site requires the involvement of at least seven proteins, encoded by hypABCDEF and a hydrogenase specific protease, encoded either by hupW or hoxW. The N2fixing cyanobacterium Nostoc sp. strain PCC 7120 may contain both an uptake and a bidirectional hydrogenase. The present study addresses the presence and expression of hypgenes in Nostoc sp. strain PCC 7120. Results: RTPCRs demonstrated that the six hypgenes together with one ORF may be transcribed as a single operon. Transcriptional start points (TSPs) were identified 280 bp upstream from hypF and 445 bp upstream of hypC, respectively, demonstrating the existence of several transcripts. In addition, five upstream ORFs located in between hupSL, encoding the small and large subunits of the uptake hydrogenase, and the hypoperon, and two downstream ORFs from the hypgenes were shown to be part of the same transcript unit. A third TSP was identified 45 bp upstream of asr0689, the first of five ORFs in this operon. The ORFs are annotated as encoding unknown proteins, with the exception of alr0692 which is identified as a NifUlike protein. Orthologues of the four ORFs asr0689alr0692, with a highly conserved genomic arrangement positioned between hupSL, and the hyp genes are found in several other N2fixing cyanobacteria, but are absent in non N2fixing cyanobacteria with only the bidirectional hydrogenase. Short conserved sequences were found in six intergenic regions of the extended hypoperon, appearing between 11 and 79 times in the genome. Conclusion: This study demonstrated that five ORFs upstream of the hypgene cluster are cotranscribed with the hypgenes, and identified three TSPs in the extended hypgene cluster in Nostoc sp. strain PCC 7120. This may indicate a function related to the assembly of a functional uptake hydrogenase, hypothetically in the assembly of the small subunit of the enzyme.
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27.
  • Al-Majdoub, Mahmoud, et al. (författare)
  • Population-level analysis to determine parameters that drive variation in the plasma metabolite profiles
  • 2018
  • Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 8:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The plasma metabolome is associated with multiple phenotypes and diseases. However, a systematic study investigating clinical determinants that control the metabolome has not yet been conducted. In the present study, therefore, we aimed to identify the major determinants of the plasma metabolite profile. We used ultra-high performance liquid chromatography (UHPLC) coupled to quadrupole time of flight mass spectrometry (QTOF-MS) to determine 106 metabolites in plasma samples from 2503 subjects in a cross-sectional study. We investigated the correlation structure of the metabolite profiles and generated uncorrelated metabolite factors using principal component analysis (PCA) and varimax rotation. Finally, we investigated associations between these factors and 34 clinical covariates. Our results suggest that liver function, followed by kidney function and insulin resistance show the strongest associations with the plasma metabolite profile. The association of specific phenotypes with several components may suggest multiple independent metabolic mechanisms, which is further supported by the composition of the associated factors. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
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28.
  • Alfoeldi, Jessica, et al. (författare)
  • The genome of the green anole lizard and a comparative analysis with birds and mammals
  • 2011
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 477:7366, s. 587-591
  • Tidskriftsartikel (refereegranskat)abstract
    • The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments(1). Among amniotes, genome sequences are available for mammals and birds(2-4), but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes(2). Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds(5). We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.
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29.
  • Allahverdiyeva, Yagut, et al. (författare)
  • NordAqua, a Nordic Center of Excellence to develop an algae-based photosynthetic production platform
  • 2021
  • Ingår i: Physiologia Plantarum. - : John Wiley & Sons. - 0031-9317 .- 1399-3054. ; 173:2, s. 507-513
  • Tidskriftsartikel (refereegranskat)abstract
    • NordAqua is a multidisciplinary Nordic Center of Excellence funded by NordForsk Bioeconomy program (2017–2022). The research center promotes Blue Bioeconomy and endeavours to reform the use of natural resources in a environmentally sustainable way. In this short communication, we summarize particular outcomes of the consortium. The key research progress of NordAqua includes (1) improving of photosynthetisis, (2) developing novel photosynthetic cell factories that function in a “solar-driven direct CO2 capture to target bioproducts” mode, (3) promoting the diversity of Nordic cyanobacteria and algae as an abundant and resilient alternative for less sustainable forest biomass and for innovative production of biochemicals, and (4) improving the bio-based wastewater purification and nutrient recycling technologies to provide new tools for integrative circular economy platforms.
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30.
  • Allard, Christina, et al. (författare)
  • Samernas rättigheter försvagas
  • 2009
  • Ingår i: Dagens Nyheter. - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)
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31.
  • Analatos, Apostolos, et al. (författare)
  • Evaluation of resection of the gastroesophageal junction and jejunal interposition (Merendino procedure) as a rescue procedure in patients with a failed redo antireflux procedure. A single-center experience
  • 2018
  • Ingår i: BMC Surgery. - : Springer Science and Business Media LLC. - 1471-2482. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Primary antireflux surgery has high success rates but 5 to 20% of patients undergoing antireflux operations can experience recurrent reflux and dysphagia, requiring reoperation. Different surgical approaches after failed fundoplication have been described in the literature. The aim of this study was to evaluate resection of the gastroesophageal junction with jejunal interposition (Merendino procedure) as a rescue procedure after failed fundoplication.Methods: All patients who underwent a Merendino procedure at the Karolinska University Hospital between 2004 and 2012 after a failed antireflux fundoplication were identified. Data regarding previous surgical history, preoperative workup, postoperative complications, subsequent investigations and re-interventions were collected retrospectively. The follow-up also included questionnaires regarding quality of life, gastrointestinal function and the dumping syndrome.Results: Twelve patients had a Merendino reconstruction. Ten patients had undergone at least two previous fundoplications, of which one patient had four such procedures. The main indication for surgery was epigastric and radiating back pain, with or without dysphagia. Postoperative complications occurred in 8/12 patients (67%). During a median follow-up of 35 months (range 20-61), four (25%) patients had an additional redo procedure with conversion to a Roux-en-Y esophagojejunostomy within 12 months, mainly due to obstructive symptoms that could not be managed conservatively or with endoscopic techniques. Questionnaires scores were generally poor in all dimensions.Conclusions: In our experience, the Merendino procedure seems to be an unsuitable surgical option for patients who require an alternative surgical reconstruction due to a failed fundoplication. However, the small number of patients included in this study as well as the small number of participants who completed the postoperative workout limits this study.
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32.
  • Angermayr, S. Andreas, et al. (författare)
  • Energy biotechnology with cyanobacteria
  • 2009
  • Ingår i: Current Opinion in Biotechnology. - : Elsevier BV. - 0958-1669 .- 1879-0429. ; 20:3, s. 257-263
  • Forskningsöversikt (refereegranskat)abstract
    • The world's future energy demand calls for a sustainable alternative for the use of fossil fuels, to restrict further global warming. Harvesting solar energy via photosynthesis is one of Nature's remarkable achievements. Existing technologies exploit this process for energy 'production' via processing of, for example, part of plant biomass into ethanol, and of algal biomass into biodiesel. Fortifying photosynthetic organisms with the ability to produce biofuels directly would bypass the need to synthesize all the complex chemicals of 'biomass'. A promising way to achieve this is to redirect cyanobacterial intermediary metabolism by channeling (Calvin cycle) intermediates into fermentative metabolic pathways. This review describes this approach via the biosynthesis of fermentation end products, like alcohols and hydrogen, driven by solar energy, from water (and CO2).
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33.
  • Antal, Taras, et al. (författare)
  • Production of H2 by sulphur-deprived cells of the unicellular cyanobacteria Gloeocapsa alpicola and Synechocystis sp. PCC 6803 during dark incubation with methane or a various extracellular pH
  • 2005
  • Ingår i: Journal of Applied Microbiology. - : Oxford University Press (OUP). - 1364-5072 .- 1365-2672. ; 98, s. 114-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To examine sulphur (S) deprivation in combination with the presence of methane (CH4) and changes in extracellular pH as a method to enhance in situ hydrogen (H2) generation during fermentation in the unicellular non-diazotrophic cyanobacteria Gloeocapsa alpicola and Synechocystis PCC 6803.Methods and Results: The level of H2 production, measured using a gas chromatography, was determined in S-deprived cells of G. alpicola and Synechocystis PCC 6803 during fermentation. Starvation on S enhanced the rate of H2 production by more than fourfold in both strains. S-deprived cyanobacteria were able to maintain maximum rate of H2 production during at least 8 h of fermentaion representing the entire dark period of a day. Increased H2 production was observed during dark anoxic incubation with a gas phase of 100% CH4 (up to four times) at lower pH of the medium (5.0-5.5)Conclusions: S-deprivation in combination with CH4, added or maybe produced by another micro-organisms, and the changes in the pH of the media can be used to further increase the specific capacity of unicellular non-N2-fixing cyanobacteria to produce H2 during fermentaion with the overall aim of applying it for outdoor photobiological H2 production.Significance and Impact of the Studies: S-deprivation with respect to H2 production is well studied in the green algae Chlamydomonas reinhardtii while its application for H2 production of cyanobacteria is novel. Similarly, the stimulation of H2 generation in the presence of CH4 opens up new possibilities to increase the H2 production. Natural gas enriched with H2 seems to be a perspective fuel and may be an intermediate step on the pathway to the exploitation of pure biohydrogen.
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34.
  •  
35.
  • Arevalo, Sergio, et al. (författare)
  • Genome Engineering by RNA-Guided Transposition for Anabaena sp. PCC 7120
  • 2024
  • Ingår i: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 13:3, s. 901-912
  • Tidskriftsartikel (refereegranskat)abstract
    • In genome engineering, the integration of incoming DNA has been dependent on enzymes produced by dividing cells, which has been a bottleneck toward increasing DNA insertion frequencies and accuracy. Recently, RNA-guided transposition with CRISPR-associated transposase (CAST) was reported as highly effective and specific in Escherichia coli. Here, we developed Golden Gate vectors to test CAST in filamentous cyanobacteria and to show that it is effective in Anabaena sp. strain PCC 7120. The comparatively large plasmids containing CAST and the engineered transposon were successfully transferred into Anabaena via conjugation using either suicide or replicative plasmids. Single guide (sg) RNA encoding the leading but not the reverse complement strand of the target were effective with the protospacer-associated motif (PAM) sequence included in the sgRNA. In four out of six cases analyzed over two distinct target loci, the insertion site was exactly 63 bases after the PAM. CAST on a replicating plasmid was toxic, which could be used to cure the plasmid. In all six cases analyzed, only the transposon cargo defined by the sequence ranging from left and right elements was inserted at the target loci; therefore, RNA-guided transposition resulted from cut and paste. No endogenous transposons were remobilized by exposure to CAST enzymes. This work is foundational for genome editing by RNA-guided transposition in filamentous cyanobacteria, whether in culture or in complex communities. [GRAPHICS] .
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36.
  • Axelsson, Rikard, 1970- (författare)
  • Cyanobacterial Hydrogen Metabolism : Transcriptional Regulation of the Hydrogenases in Filamentous Strains
  • 2003
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cyanobacteria are a heterogeneous group of phototrophic microorganisms. Many cyanobacteria have the capacity to fix atmospheric nitrogen. During the process of nitrogen fixation, molecular hydrogen is produced. Three enzymes are directly involved in hydrogen metabolism in cyanobacteria. A nitrogenase, evolving hydrogen during nitrogen-fixation, an uptake hydrogenase, recycling the hydrogen produced by nitrogenase, and a bidirectional hydrogenase that has the capacity to both take up and produce hydrogen. The main objective in this thesis was to examine the transcriptional regulation of both the uptake and the bidirectional hydrogenase in filamentous cyanobacteria.The transcriptional regulation of the uptake hydrogenase was demonstrated to be influenced by external conditions in Nostoc muscorum and Nostoc punctiforme. Nickel, molecular hydrogen, and anaerobic conditions all induced the relative amount of uptake hydrogenase transcript. In addition, a transcript could be detected in nitrogen-fixing, but not in non-nitrogen fixing conditions.The transcriptional regulation of the bidirectional hydrogenase in N. muscorum and Anabaena PCC 7120 was also examined. The relative amount of transcript from the bidirectional hydrogenase in both strains was demonstrated to increase during anaerobic conditions. Moreover, experiments using N. muscorum demonstrated that addition of nickel also increase the amount of transcript. However, no change in the relative amount of transcript from the bidirectional hydrogenase could be observed by additional hydrogen or during a shift from non-nitrogen fixing to nitrogen fixing conditions.The genes responsible for maturation of the hydrogenase were identified, cloned and sequenced in N. punctiforme. The transcription of the genes was examined and all genes were located on a single transcript. Like the uptake hydrogenase, a transcript could be detected under nitrogen-fixing but not under non-nitrogen fixing conditions. Initial studies, using microarrays, were used to analyse and compare the transcription of a large set of Anabaena PCC 7120 genes under non-nitrogen and nitrogen-fixing conditions. Both up- and down-regulated genes could be identified.This thesis advances the knowledge about the transcriptional regulation of the hydrogenases in filamentous cyanobacteria and can be used as a platform for further experiments aiming at a modified hydrogen metabolism.
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37.
  •  
38.
  • Badary, Amr, et al. (författare)
  • Glycogen Production in Marine Cyanobacterial Strain Synechococcus sp NKBG 15041c
  • 2018
  • Ingår i: Marine Biotechnology. - : Springer Science and Business Media LLC. - 1436-2228 .- 1436-2236. ; 20:2, s. 109-117
  • Tidskriftsartikel (refereegranskat)abstract
    • An important feature offered by marine cyanobacterial strains over freshwater strains is the capacity to grow in seawater, replacing the need for often-limited freshwater. However, there are only limited numbers of marine cyanobacteria that are available for genetic manipulation and bioprocess applications. The marine unicellular cyanobacteria Synechococcus sp. strain NKBG 15041c (NKBG15041c) has been extensively studied. Recombinant DNA technologies are available for this strain, and its genomic information has been elucidated. However, an investigation of carbohydrate production, such as glycogen production, would provide information for inevitable biofuel-related compound production, but it has not been conducted. In this study, glycogen production by marine cyanobacterium NKBG15041c was investigated under different cultivation conditions. NKBG15041c yielded up to 399 mu g/ml/OD730 when cells were cultivated for 168 h in nitrogen-depleted medium (marine BG11(Delta N)) after medium replacement (336 h after inoculation). Cultivation under nitrogen-limited conditions also yielded an accumulation of glycogen in NKBG15041c cells (1 mM NaNO3, 301 mu g/ml/OD730; 3 mM NaNO3, 393 mu g/ml/OD730; and 5 mM NaNO3, 328 mu g/ml/OD730) under ambient conditions. Transcriptional analyses were carried out for 13 putative genes responsible for glycogen synthesis and catabolism that were predicted based on homology analyses with Synechocystis sp. PCC 6803 (PCC6803) and Synechococcus sp. PCC7002 (PCC7002). The transcriptional analyses revealed that glycogen production in NKBG15041c under nitrogen-depleted conditions can be explained by the contribution of both increased carbon flux towards glycogen synthesis, similar to PCC6803 and PCC7002, and increased transcriptional levels of genes responsible for glycogen synthesis, which is different from the conventionally reported phenomenon, resulting in a relatively high amount of glycogen under ambient conditions compared to PCC6803 and PCC7002.
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39.
  • Baebprasert, Wipawee, et al. (författare)
  • Increased H(2) production in the cyanobacterium Synechocystis sp strain PCC 6803 by redirecting the electron supply via genetic engineering of the nitrate assimilation pathway
  • 2011
  • Ingår i: Metabolic engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 13:5, s. 610-616
  • Tidskriftsartikel (refereegranskat)abstract
    • The unicellular cyanobacterium Synechocystis sp. strain PCC 6803 contains a single bidirectional NiFe-Hox-hydrogenase, which evolves hydrogen under certain environmental conditions. The nitrate assimilation pathway is a potential competing pathway that may reduce the electron flow to the hydrogenase and thereby limit hydrogen production. To improve H(2) production, the nitrate assimilation pathway was disrupted by genetic engineering to redirect the electron flow towards the Hox-hydrogenase. Mutant strains disrupted in either nitrate reductase (Delta narB) or nitrite reductase (Delta nirA) or both nitrate reductase and nitrite reductase (Delta narB:Delta nirA) were constructed and tested for their ability to produce hydrogen. H(2) production and Hox-hydrogenase activities in all the mutant strains were higher than those in wild-type. Highest H(2) production was observed in the Delta narB:Delta nirA strain. Small changes were observed for Hox-hydrogenase enzyme activities and only minor changes in transcript levels of hoxH and hoxY were not correlated with H(2) production. The results suggest that the high rate of H(2) production observed in the Delta narB:Delta nirA strain of the cyanobacterium Synechocystis sp. strain PCC 6803 is the result of redirecting the electron supply from the nitrate assimilation pathway, through genetic engineering, towards the Hox-hydrogenase.
  •  
40.
  • Baebprasert, Wipawee, et al. (författare)
  • Na(+)-stimulated nitrate uptake with increased activity under osmotic upshift in Synechocystis sp strain PCC 6803
  • 2011
  • Ingår i: World Journal of Microbiology & Biotechnology. - : Springer Science and Business Media LLC. - 0959-3993 .- 1573-0972. ; 27:10, s. 2467-2473
  • Tidskriftsartikel (refereegranskat)abstract
    • In the non-diazotrophic cyanobacterium Synechocystis sp. strain PCC 6803, an osmolality of 30 and 40 mosmol/kg sorbitol and NaCl resulted in 3.5- and 4.5-fold increase of nitrate uptake, respectively. The NaCl-stimulated uptake was abolished by treatment with chloramphenicol. At 25 mosmol/kg or higher, NaCl induced higher nitrate uptake than sorbitol suggesting an ionic effect of Na(+). The nitrate uptake in Synechocystis showed K (s) and V (max) values of 46 mu M and 1.37 mu mol/min/mg Chl, respectively. Mutants disrupted in nitrate and nitrite reductase exhibited a decreased nitrate uptake. Ammonium, chlorate, and dl-glyceraldehyde caused a reduction of nitrate uptake. Dark treatment caused a drastic reduction of uptake by 70% suggesting an energy-dependent system. Nitrate transport was sensitive to various metabolic inhibitors including those dissipating proton gradients and membrane potential. The results suggest that nitrate uptake in Synechocystis is stimulated by Na(+) ions and requires energy provided by the functioning electron transport chain.
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41.
  • Baebprasert, Wipawee, et al. (författare)
  • Response of H-2 production and Hox-hydrogenase activity to external factors in the unicellular cyanobacterium Synechocystis sp strain PCC 6803
  • 2010
  • Ingår i: International journal of hydrogen energy. - : Elsevier BV. - 0360-3199 .- 1879-3487. ; 35:13, s. 6611-6616
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of external factors on both H-2 production and bidirectional Hox-hydrogenase activity were examined in the non-N-2-fixing cyanobacterium Synechocystis PCC 6803. Exogenous glucose and increased osmolality both enhanced H-2 production with optimal production observed at 0.4% and 20 mosmol kg(-1), respectively. Anaerobic condition for 24 h induced significant higher H(2)ase activity with cells in BC11(0) showing highest activities. Increasing the pH resulted in an increased Hox-hydrogenase activity with an optimum at pH 7.5. The Hox-hydrogenase activity gradually increased with increasing temperature from 30 degrees C to 60 degrees C with the highest activity observed at 70 degrees C. A low concentration at 100 mu M of either DTT or beta-mercaptoethanol resulted in a minor stimulation of H-2 production. beta-Mercaptoethanol added to nitrogen- and sulfur-deprived cells stimulated H-2 production significantly. The highest Hox-hydrogenase activity was observed in cells in BG11(0)-S-deprived condition and 750 mu M beta-mercaptoethanol measured at a temperature of 70 degrees C; 14.32 mu mol H-2 mg chl alpha(-1) min(-1).
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42.
  • Bannasch, Danika, et al. (författare)
  • Localization of canine brachycephaly using an across breed mapping approach
  • 2010
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3, s. e9632-
  • Tidskriftsartikel (refereegranskat)abstract
    • The domestic dog, Canis familiaris, exhibits profound phenotypic diversity and is an ideal model organism for the genetic dissection of simple and complex traits. However, some of the most interesting phenotypes are fixed in particular breeds and are therefore less tractable to genetic analysis using classical segregation-based mapping approaches. We implemented an across breed mapping approach using a moderately dense SNP array, a low number of animals and breeds carefully selected for the phenotypes of interest to identify genetic variants responsible for breed-defining characteristics. Using a modest number of affected (10-30) and control (20-60) samples from multiple breeds, the correct chromosomal assignment was identified in a proof of concept experiment using three previously defined loci; hyperuricosuria, white spotting and chondrodysplasia. Genome-wide association was performed in a similar manner for one of the most striking morphological traits in dogs: brachycephalic head type. Although candidate gene approaches based on comparable phenotypes in mice and humans have been utilized for this trait, the causative gene has remained elusive using this method. Samples from nine affected breeds and thirteen control breeds identified strong genome-wide associations for brachycephalic head type on Cfa 1. Two independent datasets identified the same genomic region. Levels of relative heterozygosity in the associated region indicate that it has been subjected to a selective sweep, consistent with it being a breed defining morphological characteristic. Genotyping additional dogs in the region confirmed the association. To date, the genetic structure of dog breeds has primarily been exploited for genome wide association for segregating traits. These results demonstrate that non-segregating traits under strong selection are equally tractable to genetic analysis using small sample numbers.
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43.
  • Barone, Giovanni Davide, et al. (författare)
  • Harnessing photosynthetic microorganisms for enhanced bioremediation of microplastics : A comprehensive review
  • 2024
  • Ingår i: ENVIRONMENTAL SCIENCE AND ECOTECHNOLOGY. - : Elsevier. - 2666-4984. ; 20
  • Forskningsöversikt (refereegranskat)abstract
    • Mismanaged plastics, upon entering the environment, undergo degradation through physicochemical and/or biological processes. This process often results in the formation of microplastics (MPs), the most prevalent form of plastic debris (<1 mm). MPs pose severe threats to aquatic and terrestrial ecosystems, necessitating innovative strategies for effective remediation. Some photosynthetic microorganisms can degrade MPs but there lacks a comprehensive review. Here we examine the specific role of photoautotrophic microorganisms in water and soil environments for the biodegradation of plastics, focussing on their unique ability to grow persistently on diverse polymers under sunlight. Notably, these cells utilise light and CO2 to produce valuable compounds such as carbohydrates, lipids, and proteins, showcasing their multifaceted environmental benefits. We address key scientific questions surrounding the utilisation of photosynthetic microorganisms for MPs and nanoplastics (NPs) bioremediation, discussing potential engineering strategies for enhanced efficacy. Our review highlights the significance of alternative biomaterials and the exploration of strains expressing enzymes, such as polyethylene terephthalate (PET) hydrolases, in conjunction with microalgal and/or cyanobacterial metabolisms. Furthermore, we delve into the promising potential of photo-biocatalytic approaches, emphasising the coupling of plastic debris degradation with sunlight exposure. The integration of microalgal-bacterial consortia is explored for biotechnological applications against MPs and NPs pollution, showcasing the synergistic effects in wastewater treatment through the absorption of nitrogen, heavy metals, phosphorous, and carbon. In conclusion, this review provides a comprehensive overview of the current state of research on the use of photoautotrophic cells for plastic bioremediation. It underscores the need for continued investigation into the engineering of these microorganisms and the development of innovative approaches to tackle the global issue of plastic pollution in aquatic and terrestrial ecosystems. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Society for Environmental Sciences, Harbin Institute of Technology, Chinese Research Academy of Environmental Sciences.
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44.
  • Barone, Giovanni Davide, et al. (författare)
  • Hints at the Applicability of Microalgae and Cyanobacteria for the Biodegradation of Plastics
  • 2020
  • Ingår i: Sustainability. - BASEL, SWITZERLAND : MDPI. - 2071-1050. ; 12:24
  • Forskningsöversikt (refereegranskat)abstract
    • Massive plastic accumulation has been taking place across diverse landscapes since the 1950s, when large-scale plastic production started. Nowadays, societies struggle with continuously increasing concerns about the subsequent pollution and environmental stresses that have accompanied this plastic revolution. Degradation of used plastics is highly time-consuming and causes volumetric aggregation, mainly due to their high strength and bulky structure. The size of these agglomerations in marine and freshwater basins increases daily. Exposure to weather conditions and environmental microflora (e.g., bacteria and microalgae) can slowly corrode the plastic structure. As has been well documented in recent years, plastic fragments are widespread in marine basins and partially in main global rivers. These are potential sources of negative effects on global food chains. Cyanobacteria (e.g., Synechocystis sp. PCC 6803, and Synechococcus elongatus PCC 7942), which are photosynthetic microorganisms and were previously identified as blue-green algae, are currently under close attention for their abilities to capture solar energy and the greenhouse gas carbon dioxide for the production of high-value products. In the last few decades, these microorganisms have been exploited for different purposes (e.g., biofuels, antioxidants, fertilizers, and 'superfood' production). Microalgae (e.g., Chlamydomonas reinhardtii, and Phaeodactylum tricornutum) are also suitable for environmental and biotechnological applications based on the exploitation of solar light. Can photosynthetic bacteria and unicellular eukaryotic algae play a role for further scientific research in the bioremediation of plastics of different sizes present in water surfaces? In recent years, several studies have been targeting the utilization of microorganisms for plastic bioremediation. Among the different phyla, the employment of wild-type or engineered cyanobacteria may represent an interesting, environmentally friendly, and sustainable option.
  •  
45.
  • Barone, Giovanni D., et al. (författare)
  • Recent developments in the production and utilization of photosynthetic microorganisms for food applications
  • 2023
  • Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 9:4
  • Forskningsöversikt (refereegranskat)abstract
    • The growing use of photosynthetic microorganisms for food and food-related applications is driving related biotechnology research forward. Increasing consumer acceptance, high sustain-ability, demand of eco-friendly sources for food, and considerable global economic concern are among the main factors to enhance the focus on the novel foods. In the cases of not toxic strains, photosynthetic microorganisms not only provide a source of sustainable nutrients but are also potentially healthy. Several published studies showed that microalgae are sources of accessible protein and fatty acids. More than 400 manuscripts were published per year in the last 4 years. Furthermore, industrial approaches utilizing these microorganisms are resulting in new jobs and services. This is in line with the global strategy for bioeconomy that aims to support sustainable development of bio-based sectors. Despite the recognized potential of the microalgal biomass value chain, significant knowledge gaps still exist especially regarding their optimized production and utilization. This review highlights the potential of microalgae and cyanobacteria for food and food-related applications as well as their market size. The chosen topics also include advanced production as mixed microbial communities, production of high-value biomolecules, photopro-duction of terpenoid flavoring compounds, their utilization for sustainable agriculture, applica-tion as source of nutrients in space, and a comparison with heterotrophic microorganisms like yeast to better evaluate their advantages over existing nutrient sources. This comprehensive assessment should stimulate further interest in this highly relevant research topic.
  •  
46.
  • Beichman, Annabel C, et al. (författare)
  • Aquatic Adaptation and Depleted Diversity : A Deep Dive into the Genomes of the Sea Otter and Giant Otter.
  • 2019
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 36:12, s. 2631-2655
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite its recent invasion into the marine realm, the sea otter (Enhydra lutris) has evolved a suite of adaptations for life in cold coastal waters, including limb modifications and dense insulating fur. This uniquely dense coat led to the near-extinction of sea otters during the 18th-20th century fur trade and an extreme population bottleneck. We used the de novo genome of the southern sea otter (E. l. nereis) to reconstruct its evolutionary history, identify genes influencing aquatic adaptation, and detect signals of population bottlenecks. We compared the genome of the southern sea otter with the tropical freshwater-living giant otter (Pteronura brasiliensis) to assess common and divergent genomic trends between otter species, and with the closely related northern sea otter (E. l. kenyoni) to uncover population-level trends. We found signals of positive selection in genes related to aquatic adaptations, particularly limb development and polygenic selection on genes related to hair follicle development. We found extensive pseudogenization of olfactory receptor genes in both the sea otter and giant otter lineages, consistent with patterns of sensory gene loss in other aquatic mammals. At the population level, the southern sea otter and the northern sea otter showed extremely low genomic diversity, signals of recent inbreeding, and demographic histories marked by population declines. These declines may predate the fur trade and appear to have resulted in an increase in putatively deleterious variants that could impact the future recovery of the sea otter.
  •  
47.
  • Bennet, Louise, et al. (författare)
  • Dubbelt så hög risk för diabetes typ 2 hos svenskar födda i Irak
  • 2015
  • Ingår i: Läkartidningen. - 0023-7205. ; 112:16, s. 1-4
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The MEDIM study reports that Immigrants from the Middle East to Sweden – independently of other diabetes related risk factors – have a twice as high type 2 diabetes risk as compared to non-immigrated Swedes. Diabetes onset occurs 6 years earlier in this group and is partly explained by family history and/or obesity. But the MEDIM study has identified that Middle Eastern background per se is an independent risk factor for earlier disease onset. Immigrants from the Middle East free of diabetes have a more pronounced insulin resistance and worse glycaemic control than non-immigrated Swedes independently of age, obesity or other risk factors for diabetes. To be able to reduce the risk of diabetes and offer an equal health care, glucose/HbA1c should be controlled on wide indications, and risk evaluation and preventive actions provided earlier for this population at high risk for type 2 diabetes. © 2015, Swedish Medical Association. All rights reserved.
  •  
48.
  • Berg, Andreas, et al. (författare)
  • Cyanobacteria as a source of hydrogen for methane formation
  • 2014
  • Ingår i: World Journal of Microbiology & Biotechnology. - : Springer Verlag (Germany). - 0959-3993 .- 1573-0972. ; 30:2, s. 539-545
  • Tidskriftsartikel (refereegranskat)abstract
    • In a study during the 1970s co-variation of nitrogenase activity and methane formation associated with Sphagnum riparium was observed. This was suggested as evidence for a possible mechanism of hydrogen transfer from cyanobacteria to methanogens. We show experimentally that such a pathway is feasible. In a series of laboratory experiments, using a hydrogenase deficient strain of the heterocystous cyanobacterium Nostoc punctiforme and the hydrogenotrophic methanogen Methanospirillum hungateii in co-cultures, increasing light intensities resulted in elevated nitrogenase activity and methane production. The increase in methane production can be directly deduced from the nitrogenase activity of the N. punctiforme based on hydrogen balance calculations. These experimental results clearly suggest the possible existence of a novel photosynthetically regulated pathway for methane formation.
  •  
49.
  •  
50.
  • Bremer, Hanna, et al. (författare)
  • ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease
  • 2018
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Dogs can spontaneously develop complex systemic autoimmune disorders, with similarities to human autoimmune disease. Autoantibodies directed at self-antigens are a key feature of these autoimmune diseases. Here we report the identification of interleukin enhancer-binding factors 2 and 3 (ILF2 and ILF3) as autoantigens in canine immune-mediated rheumatic disease. The ILF2 autoantibodies were discovered in a small, selected canine cohort through the use of human protein arrays; a method not previously described in dogs. Subsequently, ILF3 autoantibodies were also identified in the same cohort. The results were validated with an independent method in a larger cohort of dogs. ILF2 and ILF3 autoantibodies were found exclusively, and at a high frequency, in dogs that showed a speckled pattern of antinuclear antibodies on immunofluorescence. ILF2 and ILF3 autoantibodies were also found at low frequency in human patients with SLE and Sjogren's syndrome. These autoantibodies have the potential to be used as diagnostic biomarkers for canine, and possibly also human, autoimmune disease.
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