| 1. |
- Adams, Yvonne, et al.
(författare)
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3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism
- 2023
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Ingår i: ISCIENCE. - : CELL PRESS. - 2589-0042. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Lyme neuroborreliosis (LNB), a tick-borne infection caused by spirochetes within the Borrelia burgdorferi sensu lato (s.L.) complex, is among the most prevalent bacterial central nervous system (CNS) infections in Europe and the US. Here we have screened a panel of low- passage B. burgdorferi s.l. isolates using a novel, human-derived 3D blood-brain barrier (BBB)-organoid model. We show that human-derived BBB-organoids support the entry of Borrelia spirochetes, leading to swelling of the organoids and a loss of their structural integrity. The use of the BBB-organoid model highlights the organotropism between B. burgdorferi s.l. genospecies and their ability to cross the BBB contributing to CNS infection.
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| 2. |
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| 3. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 4. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 5. |
- Hendriksen, Rene S., et al.
(författare)
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Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2019, The Author(s). Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.
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| 6. |
- Mikryukov, Vladimir, et al.
(författare)
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Connecting the multiple dimensions of global soil fungal diversity
- 2023
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Ingår i: Science advances. - 2375-2548. ; 9:48
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Tidskriftsartikel (refereegranskat)abstract
- How the multiple facets of soil fungal diversity vary worldwide remains virtually unknown, hindering the management of this essential species-rich group. By sequencing high-resolution DNA markers in over 4000 topsoil samples from natural and human-altered ecosystems across all continents, we illustrate the distributions and drivers of different levels of taxonomic and phylogenetic diversity of fungi and their ecological groups. We show the impact of precipitation and temperature interactions on local fungal species richness (alpha diversity) across different climates. Our findings reveal how temperature drives fungal compositional turnover (beta diversity) and phylogenetic diversity, linking them with regional species richness (gamma diversity). We integrate fungi into the principles of global biodiversity distribution and present detailed maps for biodiversity conservation and modeling of global ecological processes.
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| 7. |
- Tedersoo, Leho, et al.
(författare)
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Global patterns in endemicity and vulnerability of soil fungi.
- 2022
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Ingår i: Global change biology. - : Wiley. - 1365-2486 .- 1354-1013. ; 28:22, s. 6696-6710
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Tidskriftsartikel (refereegranskat)abstract
- Fungi are highly diverse organisms, which provide multiple ecosystem services. However, compared with charismatic animals and plants, the distribution patterns and conservation needs of fungi have been little explored. Here, we examined endemicity patterns, global change vulnerability and conservation priority areas for functional groups of soil fungi based on six global surveys using a high-resolution, long-read metabarcoding approach. We found that the endemicity of all fungi and most functional groups peaks in tropical habitats, including Amazonia, Yucatan, West-Central Africa, Sri Lanka, and New Caledonia, with a negligible island effect compared with plants and animals. We also found that fungi are predominantly vulnerable to drought, heat and land-cover change, particularly in dry tropical regions with high human population density. Fungal conservation areas of highest priority include herbaceous wetlands, tropical forests, and woodlands. We stress that more attention should be focused on the conservation of fungi, especially root symbiotic arbuscular mycorrhizal and ectomycorrhizal fungi in tropical regions as well as unicellular early-diverging groups and macrofungi in general. Given the low overlap between the endemicity of fungi and macroorganisms, but high conservation needs in both groups, detailed analyses on distribution and conservation requirements are warranted for other microorganisms and soil organisms.
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| 8. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 9. |
- Ayres Pereira, Marina, et al.
(författare)
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Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1
- 2016
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells.
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| 10. |
- Bratulic, Sinisa, 1981, et al.
(författare)
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Noninvasive detection of any-stage cancer using free glycosaminoglycans.
- 2022
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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. ; 119:50
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Tidskriftsartikel (refereegranskat)abstract
- Cancer mortality is exacerbated by late-stage diagnosis. Liquid biopsies based on genomic biomarkers can noninvasively diagnose cancers. However, validation studies have reported ~10% sensitivity to detect stage I cancer in a screening population and specific types, such as brain or genitourinary tumors, remain undetectable. We investigated urine and plasma free glycosaminoglycan profiles (GAGomes) as tumor metabolism biomarkers for multi-cancer early detection (MCED) of 14 cancer types using 2,064 samples from 1,260 cancer or healthy subjects. We observed widespread cancer-specific changes in biofluidic GAGomes recapitulated in an in vivo cancer progression model. We developed three machine learning models based on urine (Nurine = 220 cancer vs. 360 healthy) and plasma (Nplasma = 517 vs. 425) GAGomes that can detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 with up to 62% sensitivity to stage I disease at 95% specificity. Undetected patients had a 39 to 50% lower risk of death. GAGomes predicted the putative cancer location with 89% accuracy. In a validation study on a screening-like population requiring ≥ 99% specificity, combined GAGomes predicted any cancer type with poor prognosis within 18 months with 43% sensitivity (21% in stage I; N = 121 and 49 cases). Overall, GAGomes appeared to be powerful MCED metabolic biomarkers, potentially doubling the number of stage I cancers detectable using genomic biomarkers.
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| 11. |
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| 12. |
- Clausen, Frederik Banch, et al.
(författare)
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Recommendation for validation and quality assurance of non-invasive prenatal testing for foetal blood groups and implications for IVD risk classification according to EU regulations
- 2022
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 117:2, s. 157-165
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Forskningsöversikt (refereegranskat)abstract
- Background and Objectives: Non-invasive assays for predicting foetal blood group status in pregnancy serve as valuable clinical tools in the management of pregnancies at risk of detrimental consequences due to blood group antigen incompatibility. To secure clinical applicability, assays for non-invasive prenatal testing of foetal blood groups need to follow strict rules for validation and quality assurance. Here, we present a multi-national position paper with specific recommendations for validation and quality assurance for such assays and discuss their risk classification according to EU regulations. Materials and Methods: We reviewed the literature covering validation for in-vitro diagnostic (IVD) assays in general and for non-invasive foetal RHD genotyping in particular. Recommendations were based on the result of discussions between co-authors. Results: In relation to Annex VIII of the In-Vitro-Diagnostic Medical Device Regulation 2017/746 of the European Parliament and the Council, assays for non-invasive prenatal testing of foetal blood groups are risk class D devices. In our opinion, screening for targeted anti-D prophylaxis for non-immunized RhD negative women should be placed under risk class C. To ensure high quality of non-invasive foetal blood group assays within and beyond the European Union, we present specific recommendations for validation and quality assurance in terms of analytical detection limit, range and linearity, precision, robustness, pre-analytics and use of controls in routine testing. With respect to immunized women, different requirements for validation and IVD risk classification are discussed. Conclusion: These recommendations should be followed to ensure appropriate assay performance and applicability for clinical use of both commercial and in-house assays.
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| 13. |
- Clausen, Thomas Mandel, et al.
(författare)
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A simple method for detecting oncofetal chondroitin sulfate glycosaminoglycans in bladder cancer urine
- 2020
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Ingår i: Cell Death Discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Proteoglycans in bladder tumors are modified with a distinct oncofetal chondroitin sulfate (ofCS) glycosaminoglycan that is normally restricted to placental trophoblast cells. This ofCS-modification can be detected in bladder tumors by the malarial VAR2CSA protein, which in malaria pathogenesis mediates adherence of parasite-infected erythrocytes within the placenta. In bladder cancer, proteoglycans are constantly shed into the urine, and therefore have the potential to be used for detection of disease. In this study we investigated whether recombinant VAR2CSA (rVAR2) protein could be used to detect ofCS-modified proteoglycans (ofCSPGs) in the urine of bladder cancer patients as an indication of disease presence. We show that ofCSPGs in bladder cancer urine can be immobilized on cationic nitrocellulose membranes and subsequently probed for ofCS content by rVAR2 protein in a custom-made dot-blot assay. Patients with high-grade bladder tumors displayed a marked increase in urinary ofCSPGs as compared to healthy individuals. Urine ofCSPGs decreased significantly after complete tumor resection compared to matched urine collected preoperatively from patients with bladder cancer. Moreover, ofCSPGs in urine correlated with tumor size of bladder cancer patients. These findings demonstrate that rVAR2 can be utilized in a simple biochemical assay to detect cancer-specific ofCS-modifications in the urine of bladder cancer patients, which may be further developed as a noninvasive approach to detect and monitor the disease.
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| 14. |
- Gassner, Christoph, et al.
(författare)
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International Society of Blood Transfusion Working Party on Red Cell Immunogenetics and Blood Group Terminology Report of Basel and three virtual business meetings : Update on blood group systems
- 2022
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Ingår i: Vox Sanguinis. - : Wiley. - 1423-0410 .- 0042-9007. ; 117:11, s. 1332-1344
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Under the ISBT, the Working Party (WP) for Red Cell Immunogenetics and Blood Group Terminology is charged with ratifying blood group systems, antigens and alleles. This report presents the outcomes from four WP business meetings, one located in Basel in 2019 and three held as virtual meetings during the COVID-19 pandemic in 2020 and 2021.MATERIALS AND METHODS: As in previous meetings, matters pertaining to blood group antigen nomenclature were discussed. New blood group systems and antigens were approved and named according to the serologic, genetic, biochemical and cell biological evidence presented.RESULTS: Seven new blood group systems, KANNO (defined numerically as ISBT 037), SID (038), CTL2 (039), PEL (040), MAM (041), EMM (042) and ABCC1 (043) were ratified. Two (039 and 043) were de novo discoveries, and the remainder comprised reported antigens where the causal genes were previously unknown. A further 15 blood group antigens were added to the existing blood group systems: MNS (002), RH (004), LU (005), DI (010), SC (013), GE (020), KN (022), JMH (026) and RHAG (030).CONCLUSION: The ISBT now recognizes 378 antigens, of which 345 are clustered within 43 blood group systems while 33 still have an unknown genetic basis. The ongoing discovery of new blood group systems and antigens underscores the diverse and complex biology of the red cell membrane. The WP continues to update the blood group antigen tables and the allele nomenclature tables. These can be found on the ISBT website (http://www.isbtweb.org/working-parties/red-cell-immunogenetics-and-blood-group-terminology/).
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| 15. |
- Graco-Roza, Caio, et al.
(författare)
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Distance decay 2.0 – A global synthesis of taxonomic and functional turnover in ecological communities
- 2022
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 31:7, s. 1399-1421
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Understanding the variation in community composition and species abundances (i.e., beta-diversity) is at the heart of community ecology. A common approach to examine beta-diversity is to evaluate directional variation in community composition by measuring the decay in the similarity among pairs of communities along spatial or environmental distance. We provide the first global synthesis of taxonomic and functional distance decay along spatial and environmental distance by analysing 148 datasets comprising different types of organisms and environments.Location: Global.Time period: 1990 to present.Major taxa studied: From diatoms to mammals.Method: We measured the strength of the decay using ranked Mantel tests (Mantel r) and the rate of distance decay as the slope of an exponential fit using generalized linear models. We used null models to test whether functional similarity decays faster or slower than expected given the taxonomic decay along the spatial and environmental distance. We also unveiled the factors driving the rate of decay across the datasets, including latitude, spatial extent, realm and organismal features.Results: Taxonomic distance decay was stronger than functional distance decay along both spatial and environmental distance. Functional distance decay was random given the taxonomic distance decay. The rate of taxonomic and functional spatial distance decay was fastest in the datasets from mid-latitudes. Overall, datasets covering larger spatial extents showed a lower rate of decay along spatial distance but a higher rate of decay along environmental distance. Marine ecosystems had the slowest rate of decay along environmental distances.Main conclusions: In general, taxonomic distance decay is a useful tool for biogeographical research because it reflects dispersal-related factors in addition to species responses to climatic and environmental variables. Moreover, functional distance decay might be a cost-effective option for investigating community changes in heterogeneous environments.
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| 16. |
- Hansen, Ninna Schiøler, et al.
(författare)
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Fetal hyperglycemia changes human preadipocyte function in adult life
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 102:4, s. 1141-1150
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Tidskriftsartikel (refereegranskat)abstract
- Context: Offspring of women with gestational diabetes (O-GDM) or type 1 diabetes mellitus (O-T1DM) have been exposed to hyperglycemia in utero and have an increased risk of developing metabolic disease in adulthood. Design: In total, we recruited 206 adult offspring comprising the two fetal hyperglycemic groups, O-GDM and O-T1DM, and, as a control group, offspring from the background population (O-BP). Subcutaneous fat biopsies were obtained and preadipocyte cell cultures were established from adult male O-GDM (n = 18, age 30.1 ± 2.5 years), O-T1DM (n = 18, age 31.6 ± 2.2 years), and O-BP (n = 16; age, 31.5 ± 2.7 years) and cultured in vitro. Main Outcome Measures: First, we studied in vivo adipocyte histology. Second, we studied in vitro preadipocyte leptin secretion, gene expression, and LEP DNA methylation. This was studied in combination with in vitro preadipocyte lipogenesis, lipolysis, and mitochondrial respiration. Results: We show that subcutaneous adipocytes from O-GDM are enlarged compared with O-BP adipocytes. Preadipocytes isolated from male O-GDM and O-T1DM and cultured in vitro displayed decreased LEP promoter methylation, increased leptin gene expression, and elevated leptin secretion throughout differentiation, compared with adipocytes established from male O-BP. In addition, the preadipocytes demonstrated functional defects including decreased maximal mitochondrial capacity with increased lipolysis and decreased ability to store fatty acids when challenged with 3 days of extra fatty acid supply. Conclusions: Taken together, these findings show that intrinsic epigenetic and functional changes exist in preadipocyte cultures from individuals exposed to fetal hyperglycemia who are at increased risk of developing metabolic disease.
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| 17. |
- Hansen, Steffen Foss, et al.
(författare)
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Nanotechnology meets circular economy
- 2022
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Ingår i: Nature Nanotechnology. - : Springer Science and Business Media LLC. - 1748-3387 .- 1748-3395. ; 17:7, s. 682-685
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Hansen, Steffen Foss, et al.
(författare)
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To be or not to be a nanomaterial
- 2022
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Ingår i: Journal of Nanoparticle Research. - : Springer Science and Business Media LLC. - 1388-0764 .- 1572-896X. ; 24:12
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Tidskriftsartikel (refereegranskat)abstract
- In early 2021, the new definition of the term “nanomaterial” proposed by the European Commission (EC) was subject to a stakeholder consultation and in June 2022, the EC published its updated definition. Based on an independent analysis of the different versions of the definition and the results of the stakeholder consultation, the aim of this paper is to identify key aspects to be considered when deciding whether a material should be regarded as a nanomaterial. More than 130 comments submitted during the stakeholder consultation by various organizations, companies, citizens, and authorities were analyzed. We find that the introduction of new terms such as “solid particles” has added clarity to terms used in the former definition. Our analysis shows that stakeholders seemed inclined to maintain the default number-based 50% threshold value, but were opposed to (1) the possible flexibility of varying the threshold in specific sectorial legislation, (2) the default inclusion of carbonaceous materials < 1 nm, and (3) the use of volume specific surface area (VSSA) other than for excluding materials from being defined as nanomaterials. Overall, we find that the updated definition addresses many of the limitations of the former definition. However, the updated definition also creates new challenges that will have to be addressed via development of new regulatory guidance. Apart from the relatively minor change of the VSSA threshold from 5 to 6 m2/cm3, it generally seems that no arguments from the stakeholder consultation made the EC reconsider its position. Graphical Abstract: [Figure not available: see fulltext.].
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| 19. |
- Hjort, Line, et al.
(författare)
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Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy
- 2024
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Ingår i: Clinical Epigenetics. - 1868-7075. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. Methods: To identify DMRs, we employed the bump hunter method in samples from young (9–16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28–33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. Results: One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring’s own adiposity. Conclusions: Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.
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| 20. |
- Johnsen, Sigfus J., et al.
(författare)
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A "deep" ice core from east Greenland
- 1992
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Ingår i: MoG Geoscience. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- Pilot studies on the Renland peninsula in Scoresbysund Fjord, East Greenland, indicated that the relatively small and separate Renland ice cap meets most of the criteria defining a favourable ice-core drill-site. In 1988, a Nordic expedition recovered a continuous surface-to-bedrock ice core from the summit. This relatively short core reaches deep into the past, probably throughout the last glaciation and through most of the preceding interglacial, Eem, 125,000 years B.P. The core contains detailed information on temporal changes of the coastal environment, and serves as a valuable complement to the new deep ice cores being drilled in Central Greenland. Core analyses suggest that (1) during Eemian time the East Greenland climate was at least 5ÔC warmer than now, and the precipitation 20% higher; (2) during the last glacial period, the precipitation decreased to a minimum, perhaps only 20% of the present value; (3) the post-glacial climatic optimum was 2,5ÔC warmer than now; (4) the long-term variability of the record is relatively low, due to isostatic movements in the area; and (5) from 70,000 years B.P. the Greenland glacial climate alternated between two quasi-stable stages. The latter point may reflect a chaotic feature of climate. If so, climate predictions will be difficult to access.
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| 21. |
- Khan, Zahidul, et al.
(författare)
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Plant thymidine kinase 1: a novel efficient suicide gene for malignant glioma therapy.
- 2010
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 12, s. 549-558
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Tidskriftsartikel (refereegranskat)abstract
- The prognosis for malignant gliomas remains poor, and new treatments are urgently needed. Targeted suicide gene therapy exploits the enzymatic conversion of a prodrug, such as a nucleoside analog, into a cytotoxic compound. Although this therapeutic strategy has been considered a promising regimen for central nervous system (CNS) tumors, several obstacles have been encountered such as inefficient gene transfer to the tumor cells, limited prodrug penetration into the CNS, and inefficient enzymatic activity of the suicide gene. We report here the cloning and successful application of a novel thymidine kinase 1 (TK1) from the tomato plant, with favorable characteristics in vitro and in vivo. This enzyme (toTK1) is highly specific for the nucleoside analog prodrug zidovudine (azidothymidine, AZT), which is known to penetrate the blood-brain barrier. An important feature of toTK1 is that it efficiently phosphorylates its substrate AZT not only to AZT monophosphate, but also to AZT diphosphate, with excellent kinetics. The efficiency of the toTK1/AZT system was confirmed when toTK1-transduced human glioblastoma (GBM) cells displayed a 500-fold increased sensitivity to AZT compared with wild-type cells. In addition, when neural progenitor cells were used as delivery vectors for toTK1 in intracranial GBM xenografts in nude rats, substantial attenuation of tumor growth was achieved in animals exposed to AZT, and survival of the animals was significantly improved compared with controls. The novel toTK1/AZT suicide gene therapy system in combination with stem cell-mediated gene delivery promises new treatment of malignant gliomas.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Norberg, Peter, 1974, et al.
(författare)
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Glycoprotein I of herpes simplex virus type 1 contains a unique polymorphic tandem-repeated mucin region.
- 2007
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 88:Pt 6, s. 1683-8
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Forskningsöversikt (refereegranskat)abstract
- Glycoprotein I (gI) of herpes simplex virus type 1 (HSV-1) contains a tandem repeat (TR) region including the amino acids serine and threonine, residues that can be utilized for O-glycosylation. The length of this TR region was determined for 82 clinical HSV-1 isolates and the results revealed a polymorphic distribution of two to six or eight repeated blocks with a majority harbouring between two and four repeats. Assessment of the O-glycosylation capacity of an acceptor peptide (STPSTTTSTPSTTT), representing two of the gI blocks, showed that the peptide was a universal substrate for O-glycosylation not only for the two most commonly expressed N-acetyl-d-galactosamine (GalNAc)-T1 and -T2 transferases, but also for the GalNAc-T3, -T4 and -T11 transferases. Immunoblotting of virus-infected cells showed that gI was exclusively O-glycosylated with GalNAc monosaccharides (Tn antigen). A polymorphic mucin region has not been described previously for HSV-1 and is a unique finding, as repeated blocks within gI homologues are lacking in other alphaherpesviruses.
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| 26. |
- Olsen, Yulia, et al.
(författare)
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Vascular and lung function related to ultrafine and fine particles exposure assessed by personal and indoor monitoring: a cross-sectional study
- 2014
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Ingår i: Environmental Health. - 1476-069X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to ambient air particulate matter (PM) has been linked to decline in pulmonary function and cardiovascular events possibly through inflammation. Little is known about individual exposure to ultrafine particles (UFP) inside and outside modern homes and associated health-related effects. Methods: Associations between vascular and lung function, inflammation markers and exposure in terms of particle number concentration (PNC; d = 10-300 nm) were studied in a cross-sectional design with personal and home indoor monitoring in the Western Copenhagen Area, Denmark. During 48-h, PNC and PM2.5 were monitored in living rooms of 60 homes with 81 non-smoking subjects (30-75 years old), 59 of whom carried personal monitors both when at home and away from home. We measured lung function in terms of the FEV1/FVC ratio, microvascular function (MVF) and pulse amplitude by digital artery tonometry, blood pressure and biomarkers of inflammation including C-reactive protein, and leukocyte counts with subdivision in neutrophils, eosinophils, monocytes, and lymphocytes in blood. Results: PNC from personal and stationary home monitoring showed weak correlation (r = 0.15, p = 0.24). Personal UFP exposure away from home was significantly inversely associated with MVF (1.3% decline per interquartile range, 95% confidence interval: 0.1-2.5%) and pulse amplitude and positively associated with leukocyte and neutrophil counts. The leukocyte and neutrophil counts were also positively and pulse amplitude negatively associated with total personal PNC. Indoor PNC and PM2.5 showed positive association with blood pressure and inverse association with eosinophil counts. Conclusions: The inverse association between personal exposure away from home and MVF is consistent with adverse health effects of UFP from sources outside the home and might be related to increased inflammation indicated by leukocyte counts, whereas UFP from sources in the home could have less effect.
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| 27. |
- persson, gunn, et al.
(författare)
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Från utsläppsscenarier till lokal nederbörd och översvämningsrisker
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Inom det av MSB finansierade projektet ”Nederbörd och översvämningar i framtidens Sverige − ett system till stöd för klimatanpassning” har SMHI ansvarat för hydrologisk och hydraulisk modellering samt framtagande av tidsserier med lokalt klimat för framtida förhållanden. Två metoder att bearbeta klimatdata har använts; SMHI:s Distributionsbaserad skalering (DBS) och en statistisk metod utarbetad vid Göteborgs universitet. Hydrologiska modeller har satts upp för Ätran och Torneälven och har sedan använts för beräkningar med de framtagna tidsserierna, som omfattar både SRES- och RCP-scenarier. Flöden med 100 års och 200 års återkomsttid har därefter beräknats liksom Beräknat högsta flöde (Bhf). Hydrauliska modeller för Falkenberg vid Ätran och Haparanda vid Torneälven har satts upp och beräkningar av vattennivåer har gjorts utifrån flödesberäkningarna och antaganden om havsnivåer. Därefter har översvämningsskikt applicerats på kartor. Samtliga beräkningar pekar mot ökande årsmedeltemperatur och årsmedelnederbörd i framtiden. För Ätrans avrinningsområde beräknas att antalet dygnstemperaturer kring noll grader och kring 15°C minskar till förmån för fler dagar med 5-10°C och från 15°C uppemot 25°C. Dagar med mindre än 10 mm nederbörd blir färre och dagar med 10-40 mm ökar. För Torneälvens avrinningsområde ser de riktigt låga dygnstemperaturerna ut att minska och istället blir det fler dagar med temperaturer strax under noll grader. En ökning av antalet dagar med medeltemperaturer kring 15°C ökar. Dagar med några mm nederbörd minskar och dagar med 5-25 mm ökar. Samtliga beräkningar pekar på ökad intensiv nederbörd och antalet torra dagar minskar enligt nästan alla beräkningar. Generellt sett ökar samtliga beräknade flöden för Ätran och för Torneälven ser de ut att minska mot slutet av seklet. Det dimensionerande snötäcket minskar för Ätran med 30-80%. Även för Torneälven ses minskande snötäcke i de flesta scenarier på ca 10-60%. Medeltillrinningen ser ut att öka både för Torneälven och för Ätran. Den maximala tillrinningen minskar troligen för Torneälven, vilket till stor del kan kopplas till mindre snömängder, och ökar för Ätran, vilket beror på ökad nederbörd. För Torneälven ses en förskjutning mot tidigare flödestoppar på våren, kopplat till en tidigare snösmältning. Havsvattenståndet har stor betydelse för vattennivåerna i Ätran ända upp till Tullbron. Uppströms Tullbron är det storleksordningen på flödet som styr hur hög vattennivån blir i Ätran. Havet påverkar vattennivåerna i mynningen vid Torneälven och längs kusten. Uppströms i Torneälven är det storleksordningen på flödet som styr vattennivåerna, och därmed risken för översvämning. Summary
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| 28. |
- Rigal, Sophie, et al.
(författare)
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Normoglycemia and physiological cortisone level maintain glucose homeostasis in a pancreas-liver microphysiological system
- 2024
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Ingår i: Communications Biology. - : NATURE PORTFOLIO. - 2399-3642. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Current research on metabolic disorders and diabetes relies on animal models because multi-organ diseases cannot be well studied with standard in vitro assays. Here, we have connected cell models of key metabolic organs, the pancreas and liver, on a microfluidic chip to enable diabetes research in a human-based in vitro system. Aided by mechanistic mathematical modeling, we demonstrate that hyperglycemia and high cortisone concentration induce glucose dysregulation in the pancreas-liver microphysiological system (MPS), mimicking a diabetic phenotype seen in patients with glucocorticoid-induced diabetes. In this diseased condition, the pancreas-liver MPS displays beta-cell dysfunction, steatosis, elevated ketone-body secretion, increased glycogen storage, and upregulated gluconeogenic gene expression. Conversely, a physiological culture condition maintains glucose tolerance and beta-cell function. This method was reproducible in two laboratories and was effective in multiple pancreatic islet donors. The model also provides a platform to identify new therapeutic proteins, as demonstrated with a combined transcriptome and proteome analysis. A human-cell-based pancreas-liver microphysiological system serves as a preclinical platform for studying glucose-insulin homeostasis and disease mechanisms of glucose dysregulation, offering a tool for identifying targets and testing drugs.
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| 29. |
- Sjövall, Peter, et al.
(författare)
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Imaging of distribution of topically applied drug molecules in mouse skin by combination of time-of-flight secondary ion mass spectrometry and scanning electron microscopy
- 2014
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 86:7, s. 3443-3452
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Tidskriftsartikel (refereegranskat)abstract
- In the development of topical drugs intended for local effects in the skin, one of the major challenges is to achieve drug penetration through the external barrier of the skin, stratum corneum, and secure exposure to the viable skin layers. Mass spectrometric imaging offers an opportunity to study drug penetration in a variety of skin models by mapping the spatial distribution indifferent skin layers after topical application of the drug. In this study, we used time-of-flight secondary ion mass spectrometry (TOF-SIMS) and scanning electron microscopy (SEM) to image the distribution of three drug molecules in skin tissue cross sections of inflamed mouse ear. The three compounds, roflumilast, tofacitinib, and ruxolitinib, were topically administered to the mouse ears, which were subsequently cryosectioned and thawed for the analyses. The results reveal that the combination of TOF-SIMS and SEM was beneficial for interpretation of drug distribution. SEM identified the different skin layers, while spatial distributions of all three compounds could be visualized by TOF-SIMS, showing that the drug was primarily distributed into, or on the top of, the stratum corneum. Imaging of endogenous skin components like cholesterol, phospholipids, ceramides, and free fatty acids showed distributions in good agreement with the literature. One limitation of the TOF-SIMS method is sensitivity, typically allowing for analysis in the millimolar range rather than the pharmacologically relevant micromolar range. However, the data presented demonstrate the potential of the technique for studying the penetration of drugs with different physicochemical properties in skin.
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| 30. |
- Spires, Mark, et al.
(författare)
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Snapshots of Urban and Rural Food Environments : EPOCH-Based Mapping in a High-, Middle-, and Low-Income Country from a Non-Communicable Disease Perspective
- 2020
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- A changing food environment is implicated as a primary contributor to the increasing levels of non-communicable diseases (NCDs). This study aimed to generate snapshots of selected external food environments to inform intervention strategies for NCD prevention in three countries: Uganda (low income), South Africa (middle income) and Sweden (high income), with one matched pair of urban–rural sites per country. Fifty formal and informal food retail outlets were assessed, and descriptive and comparative statistical analyses were performed. We found that formal food retail outlets in these countries had both positive and negative traits, as they were the main source of basic food items but also made unhealthy food items readily available. The Ugandan setting had predominantly informal outlets, while the Swedish setting had primarily formal outlets and South Africa had both, which fits broadly into the traditional (Uganda), mixed (South Africa) and modern (Sweden) conceptualized food systems. The promotion of unhealthy food products was high in all settings. Uganda had the highest in-community advertising, followed by South Africa and Sweden with the lowest, perhaps related to dierences in regulation and implementation. The findings speak to the need to address contextual dierences in NCD-related health interventions by incorporating strategies that address the food environment, and for a critical look at regulations that tackle key environment-related factors of food on a larger scale.
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| 31. |
- Tarp, Julie Bjerre, et al.
(författare)
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Vascular function in adults with cyanotic congenital heart disease
- 2020
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Ingår i: IJC Heart and Vasculature. - : Elsevier BV. - 2352-9067. ; 30
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with cyanotic congenital heart disease (CCHD) may have a low burden of atherosclerosis. Endothelial dysfunction is an early stage of atherosclerosis and endothelial function is previously studied in smaller CCHD groups with different techniques and variable results. We aimed to examine endothelial function and carotid atherosclerosis in a larger group of CCHD patients. Methods: This multicentre study assessed endothelial function in adults with CCHD and controls by measuring the dilatory response of the brachial artery to post-ischemic hyperaemia (endothelium-dependent flow-mediated-vasodilatation (FMD)), and to nitroglycerin (endothelium-independent nitroglycerin-induced dilatation (NID)). Flow was measured at baseline and after ischaemia (reactive hyperaemia). Carotid-intima-media-thickness (CIMT), prevalence of carotid plaque and plaque thickness (cPT-max) were evaluated ultrasonographically. Lipoproteins, inflammatory and vascular markers, including sphingosine-1-phosphate (S1P) were measured. Results: Forty-five patients with CCHD (median age 50 years) and 45 matched controls (median age 52 years) were included. The patients presented with lower reactive hyperaemia (409 ± 114% vs. 611 ± 248%, p < 0.0001), however preserved FMD response compared to controls (106.5 ± 8.3% vs. 106.4 ± 6.1%, p = 0.95). In contrast, NID was lower in the patients (110.5 ± 6.1% vs. 115.1 ± 7.4%, p = 0.053). There was no difference in CIMT, carotid plaque or cPT-max. The patients presented with lower high-density-lipoprotein cholesterol, and higher level of inflammatory markers and S1P. Conclusion: Adults with CCHD had preserved FMD in the brachial artery, but impaired NID response and lower reactive hyperaemia than controls. The preserved FMD and the comparable prevalence of carotid atherosclerosis indicate that CCHD patients have the same risk of atherosclerosis as controls.
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| 32. |
- Tedersoo, L., et al.
(författare)
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The Global Soil Mycobiome consortium dataset for boosting fungal diversity research
- 2021
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Ingår i: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 111, s. 573-588
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Tidskriftsartikel (refereegranskat)abstract
- Fungi are highly important biotic components of terrestrial ecosystems, but we still have a very limited understanding about their diversity and distribution. This data article releases a global soil fungal dataset of the Global Soil Mycobiome consortium (GSMc) to boost further research in fungal diversity, biogeography and macroecology. The dataset comprises 722,682 fungal operational taxonomic units (OTUs) derived from PacBio sequencing of full-length ITS and 18S-V9 variable regions from 3200 plots in 108 countries on all continents. The plots are supplied with geographical and edaphic metadata. The OTUs are taxonomically and functionally assigned to guilds and other functional groups. The entire dataset has been corrected by excluding chimeras, index-switch artefacts and potential contamination. The dataset is more inclusive in terms of geographical breadth and phylogenetic diversity of fungi than previously published data. The GSMc dataset is available over the PlutoF repository.
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| 33. |
- Williams, Jessica S, et al.
(författare)
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Evidence that processing of ribonucleotides in DNA by topoisomerase 1 is leading-strand specific
- 2015
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 22:4, s. 291-U35
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotides incorporated during DNA replication are removed by RNase H2-dependent ribonucleotide excision repair (RER). In RER-defective yeast, topoisomerase 1 (Top1) incises DNA at unrepaired ribonucleotides, initiating their removal, but this is accompanied by RNA-DNA-damage phenotypes. Here we show that these phenotypes are incurred by a high level of ribonucleotides incorporated by a leading strand-replicase variant, DNA polymerase (Pol) ɛ, but not by orthologous variants of the lagging-strand replicases, Pols α or δ. Moreover, loss of both RNases H1 and H2 is lethal in combination with increased ribonucleotide incorporation by Pol ɛ but not by Pols α or δ. Several explanations for this asymmetry are considered, including the idea that Top1 incision at ribonucleotides relieves torsional stress in the nascent leading strand but not in the nascent lagging strand, in which preexisting nicks prevent the accumulation of superhelical tension.
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| 34. |
- Kanai, M, et al.
(författare)
-
- 2023
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