| 11. |
- Alneberg, Johannes, et al.
(författare)
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Genomes from uncultivated prokaryotes : a comparison of metagenome-assembled and single-amplified genomes
- 2018
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Ingår i: Microbiome. - : BioMed Central. - 2049-2618. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prokaryotes dominate the biosphere and regulate biogeochemical processes essential to all life. Yet, our knowledge about their biology is for the most part limited to the minority that has been successfully cultured. Molecular techniques now allow for obtaining genome sequences of uncultivated prokaryotic taxa, facilitating in-depth analyses that may ultimately improve our understanding of these key organisms. Results: We compared results from two culture-independent strategies for recovering bacterial genomes: single-amplified genomes and metagenome-assembled genomes. Single-amplified genomes were obtained from samples collected at an offshore station in the Baltic Sea Proper and compared to previously obtained metagenome-assembled genomes from a time series at the same station. Among 16 single-amplified genomes analyzed, seven were found to match metagenome-assembled genomes, affiliated with a diverse set of taxa. Notably, genome pairs between the two approaches were nearly identical (average 99.51% sequence identity; range 98.77-99.84%) across overlapping regions (30-80% of each genome). Within matching pairs, the single-amplified genomes were consistently smaller and less complete, whereas the genetic functional profiles were maintained. For the metagenome-assembled genomes, only on average 3.6% of the bases were estimated to be missing from the genomes due to wrongly binned contigs. Conclusions: The strong agreement between the single-amplified and metagenome-assembled genomes emphasizes that both methods generate accurate genome information from uncultivated bacteria. Importantly, this implies that the research questions and the available resources are allowed to determine the selection of genomics approach for microbiome studies.
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| 12. |
- Bergenmar, Jenny, 1973, et al.
(författare)
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Bästa författarinna, Högtärade Dr. Lagerlöf, Kära sagotant! Om allmänhetens läsning av Selma Lagerlöf
- 2013
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Ingår i: Läsning. red. Jenny Björkman & Björn Fjaestad. - 9789170611278 ; , s. 50-59
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Receptionshistoria riktar ofta av praktiska skäl in sig på professionella läsare, framförallt kritiker som vittnar om sin läsning i tillgänglig, tryckt form. Men intresset för andra läsarter och läsargrupper i historisk tid växer stadigt. Problemet är bara att uppgifter om den bredare publikens läsning är mer svåra att få tag på. De finns till exempel i dagböcker och i brev − källor som sällan bevarats. I RJ-projektet ”Läsarnas Lagerlöf. Allmänhetens brev till Selma Lagerlöf” har vi dock tillgång till över 40 000 brev till Selma Lagerlöf. Breven härrör delvis från kolleger, släkt och vänner och denna del av materialet har ofta varit föremål för forskningens intresse. Men merparten av breven är från en svensk och utländsk allmänhet. För läsforskningen ger därför brevsamlingen mycket goda möjligheter att belysa frågor om hur människor använde litteraturen; vad den betydde och när, hur, varför och var den lästes. Materialet är inte bara stort, det är också anmärkningsvärt heterogent. Män och kvinnor från olika landsändar, stad och land, av olika klasser och ålder skrev till Selma Lagerlöf. Artikeln ger exempel visa på olika läsarter som gör sig gällande i breven och i frågan om läsning i olika läsargemenskaper diskuteras.
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| 13. |
- Fotaki, Grammatiki, et al.
(författare)
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Cancer vaccine based on a combination of an infection-enhanced adenoviral vector and pro-inflammatory allogeneic DCs leads to sustained antigen-specific immune responses in three melanoma models
- 2018
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Ingår i: Oncoimmunology. - 2162-4011 .- 2162-402X. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Autologous patient-derived dendritic cells (DCs) modified ex vivo to present tumor-associated antigens (TAAs) are frequently used as cancer vaccines. However, apart from the stringent logistics in producing DCs on a patient basis, accumulating evidence indicate that ex vivo engineered DCs are poor in migration and in fact do not directly present TAA epitopes to naïve T cells in vivo. Instead, it is proposed that bystander host DCs take up material from vaccine-DCs, migrate and subsequently initiate antitumor T-cell responses. We used mouse models to examine the possibility of using pro-inflammatory allogeneic DCs (alloDCs) to activate host DCs and enable them to promote antigen-specific T-cell immunity. We found that alloDCs were able to initiate host DC activation and migration to draining lymph node leading to T-cell activation. The pro-inflammatory milieu created by alloDCs also led to recruitment of NK cells and neutrophils at the site of injection. Vaccination with alloDCs combined with Ad5M(gp100), an infection-enhanced adenovirus encoding the human melanoma-associated antigen gp100 resulted in generation of CD8+ T cells with a T-cell receptor (TCR) specific for the gp10025-33 epitope (gp100-TCR+). Ad5M(gp100)-alloDC vaccination in combination with transfer of gp100-specific pmel-1 T cells resulted in prolonged survival of B16-F10 melanoma-bearing mice and altered the composition of the tumor microenvironment (TME). We hereby propose that alloDCs together with TAA- or neoepitope-encoding Ad5M can become an “off-the-shelf” cancer vaccine, which can reverse the TME-induced immunosuppression and induce host cellular anti-tumor immune responses in patients without the need of a time-consuming preparation step of autologous DCs.
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| 14. |
- Hedberg, Yolanda, 1985-, et al.
(författare)
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Interaction of Albumin and Fibrinogen with Stainless Steel : Influence of Sequential Exposure and Protein Aggregation on Metal Release and Corrosion Resistance
- 2017
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Ingår i: Corrosion. - : NATL ASSOC CORROSION ENG. - 0010-9312 .- 1938-159X. ; 73:12
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Tidskriftsartikel (refereegranskat)abstract
- Corrosion and metal release mechanisms of the biomedical stainless steel grade Type 316L are at human-relevant biological conditions not fully understood. This study focuses on its corrosion properties and release of iron (Fe), chromium (Cr), manganese (Mn), and nickel (Ni) into simulated physiological solutions at pH 7.4 in the presence of proteins. Parallel studies were performed on stainless steel Type 303 containing a substantial amount of MnS inclusions. Metal release studies were performed in phosphate buffered saline (PBS) for 4 h and 24 h at 37 degrees C with or without different concentrations of bovine serum albumin (BSA), fibrinogen from bovine plasma (Fbn), or mixtures of the same. Studies were in addition performed after 1, 4, 6, and 24 h in solutions that were partially replenished after 5 h in order to investigate whether any Vroman effect (exchange of adsorbed proteins by proteins of higher binding affinity) could influence the extent of released metals in solution. This was performed at physiological concentrations of BSA (40 g/L) and Fbn (2.67 g/L) in PBS, and for reference solutions of PBS, PBS with 40 g/L BSA, and PBS with 2.67 g/L Fbn. Changes in open-circuit potential and linear polarization resistance were investigated for the same conditions. After exposure, the exposed surfaces were rinsed and investigated ex situ by means of x-ray photoelectron spectroscopy and infrared reflection absorption spectroscopy. Metal-protein complexation-induced metal release mechanisms were found to be most pronounced for Type 316L and the release of Fe, Cr, and Ni. Fibrinogen adsorbed differently onto Type 303 (thicker conformation of adsorbed proteins) as compared with Type 316L and occasionally induced corrosion events for Type 303. Mn was mostly released from inclusions present in the Type 303 alloy, most probably via non-electrochemical mechanisms. A Vroman effect was observed for both grades. A significant extent of precipitation of metal-rich protein aggregates influenced the metal release measurements in solution and resulted in an underestimation of the total amount of released metals from the stainless steel grades.
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| 15. |
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| 16. |
- Karlsson, Anna, et al.
(författare)
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Gene Expression Profiling of Large Cell Lung Cancer Links Transcriptional Phenotypes to the New Histological WHO 2015 Classification
- 2017
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Ingår i: Journal of Thoracic Oncology. - : ELSEVIER SCIENCE INC. - 1556-0864 .- 1556-1380. ; 12:8, s. 1257-1267
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Large cell lung cancer (LCLC) and large cell neuroendocrine carcinoma (LCNEC) constitute a small proportion of NSCLC. The WHO 2015 classification guidelines changed the definition of the debated histological subtype LCLC to be based on immunomarkers for adenocarcinoma and squamous cancer. We sought to determine whether these new guidelines also translate into the transcriptional landscape of lung cancer, and LCLC specifically.Methods: Gene expression profiling was performed by using Illumina V4 HT12 microarrays (Illumina, San Diego, CA) on samples from 159 cases (comprising all histological subtypes, including 10 classified as LCLC WHO 2015 and 14 classified as LCNEC according to the WHO 2015 guidelines), with complimentary mutational and immunohistochemical data. Derived transcriptional phenotypes were validated in 199 independent tumors, including six WHO 2015 LCLCs and five LCNECs.Results: Unsupervised analysis of gene expression data identified a phenotype comprising 90% of WHO 2015 LCLC tumors, with characteristics of poorly differentiated proliferatiVe cancer, a 90% tumor protein p53 gene (TP53) mutation rate, and lack of well-known NSCLC oncogene driver alterations. Validation in independent data confirmed aggregation of WHO 2015 LCLCs in the specific phenotype. For LCNEC tumors, the unsupervised gene expression analysis suggested two different transcriptional patterns corresponding to a proposed genetic division of LCNEC tumors into SCLC-like and NSCLC-like cancer on the basis of TP53 and retinoblastoma 1 gene (RB1) alteration patterns.Conclusions: Refined classification of LCLC has implications for diagnosis, prognostics, and therapy decisions. Our molecular analyses support the WHO 2015 classification of LCLC and LCNEC tumors, which herein follow different tumorigenic paths and can accordingly be stratified into different transcriptional subgroups, thus linking diagnostic immunohistochemical staining driven classification with the transcriptional landscape of lung cancer.
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| 17. |
- Karlsson, Anna, 1985-, et al.
(författare)
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The effect of tinzaparin on biomarkers in FIGO stages III-IV ovarian cancer patients undergoing neoadjuvant chemotherapy – the TABANETOC trial: study protocol for a randomized clinical multicenter trial
- 2024
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Ingår i: Acta Oncologica. - Uppsala : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 580-585
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis.Purpose: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT.Material and methods: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured.Patients: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0–1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants.Interpretation: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.
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| 18. |
- Karlsson, Erik A., et al.
(författare)
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Synthesis and Electron-Transfer Processes in a New Family of Ligands for Coupled Ru-Mn2 Complexes
- 2014
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Ingår i: ChemPlusChem. - : Wiley. - 2192-6506. ; 79:7, s. 936-950
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Tidskriftsartikel (refereegranskat)abstract
- A series of [Ru(bpy)(3)](2+)-type (bpy= 2,2'-bipyridine) photosensitisers have been coupled to a ligand for Mn, which is expected to give a dinuclear complex that is active as a water oxidation catalyst. Unexpectedly, photophysical studies showed that the assemblies had very short lived excited states and that the decay patterns were complex and strongly dependent on pH. One dyad was prepared that was capable of catalysing chemical water oxidation by using [Ru(bpy)(3)](3+) as an oxidant. However, photochemical water oxidation in the presence of an external electron acceptor failed, presumably because the short excited-state lifetime precluded initial electron transfer to the added acceptor. The photophysical behaviour could be explained by the presence of an intricate excited-state manifold, as also suggested by time-dependent DFT calculations.
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| 19. |
- Karlsson, Lars O, 1975, et al.
(författare)
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Constitutive PGC-1 alpha overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Aerobic exercise prevents age-dependent decline in cognition and hippocampal neurogenesis. The transcription factor peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1 alpha) mediates many of the exercise-induced benefits in skeletal muscle, including the release of factors into the circulation with neurotrophic effects. We use a transgenic mouse model with muscle-specific overexpression of PGC-1 alpha to study the contribution of chronic muscle activation on exercise-induced effects on hippocampal neurogenesis in aging. Young and old transgenic and wild type animals of both sexes displayed a robust age-related reduction in newborn BrdU+-cells, immature neurons (DCX+-cells) and new mature BrdU(+)/NeuN(+)-neurons in the dentate gyrus. No differences were detected between genotypes or sexes. Analysis of serum proteins showed a tendency towards increased levels of myokines and reduced levels of pro-inflammatory cytokines for transgenic animals, but only musclin was found to be significantly up-regulated in transgenic animals. We conclude that constitutive muscular overexpression of PGC-1 alpha, despite potent systemic changes, is insufficient for mimicking exercise-induced effects on hippocampal neurogenesis in aging. Continued studies are required to investigate the complex molecular mechanisms by which circulating signals could mediate exercise-induced effects on the central nervous system in disease and aging, with the aim of discovering new therapeutic possibilities for patients.
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| 20. |
- Karlsson, Maria, 1985, et al.
(författare)
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Reconstitution of water channel function of an aquaporin overexpressed and purified from Pichia pastoris.
- 2003
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Ingår i: FEBS Letters. - 1873-3468 .- 0014-5793. ; 537:1-3, s. 68-72
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Tidskriftsartikel (refereegranskat)abstract
- The aquaporin PM28A is one of the major integral proteins in spinach leaf plasma membranes. Phosphorylation/dephosphorylation of Ser274 at the C-terminus and of Ser115 in the first cytoplasmic loop has been shown to regulate the water channel activity of PM28A when expressed in Xenopus oocytes. To understand the mechanisms of the phosphorylation-mediated gating of the channel the structure of PM28A is required. In a first step we have used the methylotrophic yeast Pichia pastoris for expression of the pm28a gene. The expressed protein has a molecular mass of 32462 Da as determined by matrix-assisted laser desorption ionization-mass spectrometry, forms tetramers as revealed by electron microscopy and is functionally active when reconstituted in proteoliposomes. PM28A was efficiently solubilized from urea- and alkali-stripped Pichia membranes by octyl-beta-D-thioglucopyranoside resulting in a final yield of 25 mg of purified protein per liter of cell culture.
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