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Sökning: WFRF:(Sundqvist M.) > (2020-2023)

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  • Pilotto, Francesca, et al. (författare)
  • Meta-analysis of multidecadal biodiversity trends in Europe
  • 2020
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Local biodiversity trends over time are likely to be decoupled from global trends, as local processes may compensate or counteract global change. We analyze 161 long-term biological time series (15-91 years) collected across Europe, using a comprehensive dataset comprising ~6,200 marine, freshwater and terrestrial taxa. We test whether (i) local long-term biodiversity trends are consistent among biogeoregions, realms and taxonomic groups, and (ii) changes in biodiversity correlate with regional climate and local conditions. Our results reveal that local trends of abundance, richness and diversity differ among biogeoregions, realms and taxonomic groups, demonstrating that biodiversity changes at local scale are often complex and cannot be easily generalized. However, we find increases in richness and abundance with increasing temperature and naturalness as well as a clear spatial pattern in changes in community composition (i.e. temporal taxonomic turnover) in most biogeoregions of Northern and Eastern Europe. The global biodiversity decline might conceal complex local and group-specific trends. Here the authors report a quantitative synthesis of longterm biodiversity trends across Europe, showing how, despite overall increase in biodiversity metric and stability in abundance, trends differ between regions, ecosystem types, and taxa.
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  • Andreasson, A., et al. (författare)
  • Fosfomycin versus Ciprofloxacin as transrectal prostatebiopsy antibiotic prophylaxis an open randomized controlled multicenter drug trial
  • 2023
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 83:Suppl. 1, s. S180-S180
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction & Objectives: Antibiotic prophylaxis are administered as a routine to decrease the risk for septic complications following transrectal prostate biopsy. Fosfomycin administered 1 h or more prior to biopsy has equal or better infectious complication rates as compared to Ciprofloxacin in both prospective and retrospective studies from countries with high rates of antibiotic resistance. The aim of this study was to investigate if Fosfomycin administered immediately prior to prostate biopsy was as effective as Ciprofloxacin in Sweden, a country with low rates of antibiotic resistance.Materials & Methods: A randomized, controlled, open, multicenter, non-inferiority-study including men of all ages undergoing transrectal prostate biopsy was performed in the urology departments of three Swedish hospitals. The total number of patients were planned for 3448, divided into low and high infection risk groups. The low-risk group was randomized to either one dose of Fosfomycin 3g or Ciprofloxacin 750mg before biopsy. The high-risk group was randomized to either two doses of Fosfomycin 3g prior to biopsy and one more 24 h after biopsy or Ciprofloxacin 500mg once prior to biopsy and then twice daily for three days. The drugs were administered orally. All patients had a rectal swab for culture before and after biopsy. The endpoint was hospitalisation due to urinary tract infection within 14 days from biopsy, follow-up was performed with a phone interview.Results: The safety board prematurely interrupted the study after 42 included patients due to an unusual high number of hospitalisations. Four out of 20 patients (20%), three in the low-risk group and one in the high-risk group, had been hospitalised due to urosepsis in the Fosfomycin group. One further patient described fever symptoms but did not seek health care. No patient in the Ciprofloxacin group (n=21) described symptoms of infection from the urinary tract. One patient was lost to follow-up. A one-sided binomial test showed a p-value of <0.001. Two of the four hospitalised patients had a positive blood culture for Pseudomonas Aeruginosa and one had a positive rectal swab culture for Pseudomonas species both before and after biopsy.Conclusions: The study does not support the use of Fosfomycin administered immediately prior to prostate biopsy. The results may have been affected by the unexpected high number of Pseudomonas infections, a bacteria where Fosfomycin often lack effect. If Fosfomycin is to be used it should be with caution if Pseudomonas has been seen in earlier cultures
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  • Borrega, M., et al. (författare)
  • Utilizing and Valorizing Oat and Barley Straw as an Alternative Source of Lignocellulosic Fibers
  • 2022
  • Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 15:21
  • Tidskriftsartikel (refereegranskat)abstract
    • The transition to sustainable, biodegradable, and recyclable materials requires new sources of cellulose fibers that are already used in large volumes by forest industries. Oat and barley straws provide interesting alternatives to wood fibers in lightweight material applications because of their similar chemical composition. Here we investigate processing and material forming concepts, which would enable strong fiber network structures for various applications. The idea is to apply mild pretreatment processing that could be distributed locally so that the logistics of the raw material collection could be made efficient. The actual material production would then combine foam-forming and hot-pressing operations that allow using all fractions of fiber materials with minimal waste. We aimed to study the technical features of this type of processing on a laboratory scale. The homogeneity of the sheet samples was very much affected by whether the raw material was mechanically refined or not. Straw fibers did not form a bond spontaneously with one another after drying the sheets, but their effective bonding required a subsequent hot pressing operation. The mechanical properties of the formed materials were at a similar level as those of the conventional wood-fiber webs. In addition to the technical aspects of materials, we also discuss the business opportunities and system-level requirements of using straw as an alternative source of lignocellulosic fibers. 
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  • Lindén, Elin, et al. (författare)
  • Circum-Arctic distribution of chemical anti-herbivore compounds suggests biome-wide trade-off in defence strategies in Arctic shrubs
  • 2022
  • Ingår i: Ecography. - : John Wiley & Sons. - 0906-7590 .- 1600-0587. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • Spatial variation in plant chemical defence towards herbivores can help us understand variation in herbivore top–down control of shrubs in the Arctic and possibly also shrub responses to global warming. Less defended, non-resinous shrubs could be more influenced by herbivores than more defended, resinous shrubs. However, sparse field measurements limit our current understanding of how much of the circum-Arctic variation in defence compounds is explained by taxa or defence functional groups (resinous/non-resinous). We measured circum-Arctic chemical defence and leaf digestibility in resinous (Betula glandulosa, B. nana ssp. exilis) and non-resinous (B. nana ssp. nana, B. pumila) shrub birches to see how they vary among and within taxa and functional groups. Using liquid chromatography–mass spectrometry (LC–MS) metabolomic analyses and in vitro leaf digestibility via incubation in cattle rumen fluid, we analysed defence composition and leaf digestibility in 128 samples from 44 tundra locations.We found biogeographical patterns in anti-herbivore defence where mean leaf triterpene concentrations and twig resin gland density were greater in resinous taxa and mean concentrations of condensing tannins were greater in non-resinous taxa. This indicates a biome-wide trade-off between triterpene- or tannin-dominated defences. However, we also found variations in chemical defence composition and resin gland density both within and among functional groups (resinous/non-resinous) and taxa, suggesting these categorisations only partly predict chemical herbivore defence. Complex tannins were the only defence compounds negatively related to in vitro digestibility, identifying this previously neglected tannin group as having a potential key role in birch anti-herbivore defence.We conclude that circum-Arctic variation in birch anti-herbivore defence can be partly derived from biogeographical distributions of birch taxa, although our detailed mapping of plant defence provides more information on this variation and can be used for better predictions of herbivore effects on Arctic vegetation.
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  • Sundqvist, Martina, et al. (författare)
  • Anti-neutrophil cytoplasmic antibodies (ANCA): Antigen interactions and downstream effects.
  • 2020
  • Ingår i: Journal of leukocyte biology. - 1938-3673. ; 108:2, s. 617-626
  • Forskningsöversikt (refereegranskat)abstract
    • Neutrophils are the most abundant leukocytes in circulation and are key "first responders" in the immune response to infectious and non-infectious stimuli. Unlike other immune cells, neutrophils can mount a robust response (including a change in surface markers and the production of extracellular traps and reactive oxygen species) just minutes after sensing a disturbance. It has been speculated that, in some individuals, the activation of neutrophils inadvertently leads to the generation of anti-neutrophil cytoplasmic autoantibodies (ANCA) against particular neutrophil proteins (antigens) such as myeloperoxidase (MPO) and proteinase 3 (PR3). In these individuals, continuous ANCA-antigen interactions are thought to drive persistent activation of neutrophils, chronic immune activation, and disease, most notably, small vessel vasculitis. There are significant gaps however in our understanding of the underlying mechanisms and even the pathogenicity of ANCA given that vasculitis can develop in the absence of ANCA, and that ANCA have been found in circulation in other conditions with no apparent contribution to disease. These gaps are particularly evident in the context of human studies. Herein, we review knowledge on neutrophil-derived ANCA antigens PR3 and MPO, ANCA generation, and ANCA-antigen interaction(s) that may promote immune activation and disease.
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  • Asayama, Shinichiro, et al. (författare)
  • Three institutional pathways to envision the future of the IPCC
  • 2023
  • Ingår i: Nature Climate Change. - : Nature Portfolio. - 1758-678X .- 1758-6798. ; 13:9, s. 877-880
  • Tidskriftsartikel (refereegranskat)abstract
    • The IPCC has been successful at building its scientific authority, but it will require institutional reform for staying relevant to new and changing political contexts. Exploring a range of alternative future pathways for the IPCC can help guide crucial decisions about redefining its purpose.
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  • Berkolaiko, G., et al. (författare)
  • Computing Nodal Deficiency with a Refined Dirichlet-to-Neumann Map
  • 2022
  • Ingår i: Journal of Geometric Analysis. - : Springer Science and Business Media LLC. - 1050-6926 .- 1559-002X. ; 32:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent work of the authors and their collaborators has uncovered fundamental connections between the Dirichlet-to-Neumann map, the spectral flow of a certain family of self-adjoint operators, and the nodal deficiency of a Laplacian eigenfunction (or an analogous deficiency associated to a non-bipartite equipartition). Using a refined construction of the Dirichlet-to-Neumann map, we strengthen all of these results, in particular getting improved bounds on the nodal deficiency of degenerate eigenfunctions. Our framework is very general, allowing for non-bipartite partitions, non-simple eigenvalues, and non-smooth nodal sets. Consequently, the results can be used in the general study of spectral minimal partitions, not just nodal partitions of generic Laplacian eigenfunctions.
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  • Blume-Werry, Gesche, 1985-, et al. (författare)
  • Invasive earthworms unlock arctic plant nitrogen limitation
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Arctic plant growth is predominantly nitrogen (N) limited. This limitation is generally attributed to slow soil microbial processes due to low temperatures. Here, we show that arctic plant-soil N cycling is also substantially constrained by the lack of larger detritivores (earthworms) able to mineralize and physically translocate litter and soil organic matter. These new functions provided by earthworms increased shrub and grass N concentration in our common garden experiment. Earthworm activity also increased either the height or number of floral shoots, while enhancing fine root production and vegetation greenness in heath and meadow communities to a level that exceeded the inherent differences between these two common arctic plant communities. Moreover, these worming effects on plant N and greening exceeded reported effects of warming, herbivory and nutrient addition, suggesting that human spreading of earthworms may lead to substantial changes in the structure and function of arctic ecosystems. Arctic plant growth is predominantly nitrogen limited, where the slow nitrogen turnover in the soil is commonly attributed to the cold arctic climate. Here the authors show that the arctic plant-soil nitrogen cycling is also constrained by the lack of larger detritivores like earthworms.
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  • Bowers, Sarah M, et al. (författare)
  • Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression.
  • 2022
  • Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein.Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7.In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2.The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2.
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  • El-Tawil, Asmaa A., et al. (författare)
  • Self-Reduction Behavior of Bio-Coal Containing Iron Ore Composites
  • 2020
  • Ingår i: Metals. - : MDPI. - 2075-4701. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The utilization of CO2 neutral carbon instead of fossil carbon is one way to mitigate CO2 emissions in the steel industry. Using reactive reducing agent, e.g., bio-coal (pre-treated biomass) in iron ore composites for the blast furnace can also enhance the self-reduction. The current study aims at investigating the self-reduction behavior of bio-coal containing iron ore composites under inert conditions and simulated blast furnace thermal profile. Composites with and without 10% bio-coal and sufficient amount of coke breeze to keep the C/O molar ratio equal to one were mixed and Portland cement was used as a binder. The self-reduction of composites was investigated by thermogravimetric analyses under inert atmosphere. To explore the reduction progress in each type of composite vertical tube furnace tests were conducted in nitrogen atmosphere up to temperatures selected based on thermogravimetric results. Bio-coal properties as fixed carbon, volatile matter content and ash composition influence the reduction of iron oxide. The reduction of the bio-coal containing composites begins at about 500 °C, a lower temperature compared to that for the composite with coke as only carbon source. The hematite was successfully reduced to metallic iron at 850 °C by using bio-coal, whereas with coke as a reducing agent temperature up to 1100 °C was required.
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  • Hellmer, Erica, 1980- (författare)
  • Att bevara för att använda? : Om användares och användninges betydelse i arkivet
  • 2023
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In times of increasing demands of access and use of records and archives, among the current political and private initiatives of both efficiency and innovation, and among developments of e-services and digitalization, new participatory initiatives are created. In the current times, as both users and potential users are gaining bigger roles as co-creators of records, it sets new demands on how these participatory perspectives could be contextualized in the archival practice.The aim of the thesis was to extend the knowledge of users, use of archives and archival records. Presented in the thesis, several studies have been conducted with the purpose of exploring how users and use are described in the literature of archival science, how use have been considered by different professions when analogue processes turn digital, and exploring what dictates the need of use. The studies have had a qualitative stance where the methods of data collection have consisted of interviews and a group interview, a focus group, a systematic literature review, and a participatory observation.The results show that the development of e-services is based on the need of the end-users/customers and that there is a risk that the role of the archival profession may disappear behind political incentives. Results also show that ‘user’ is a concept that is utterly bound to the heterogeneous contexts in which they are conceptualized, and that the user studies conducted within the archival domain elucidates the importance of gaining knowledge of the users’ perception and behavior. The thesis also shows that the concept of societal embeddedness as an analytical tool can be used to visualize the need of use of records. This can be used as a way to describe and contextualize the user perspective in a broader societal context.
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  • Prager, C. M., et al. (författare)
  • Climate and multiple dimensions of plant diversity regulate ecosystem carbon exchange along an elevational gradient
  • 2021
  • Ingår i: Ecosphere. - : Wiley. - 2150-8925. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The impacts of warming on communities and ecosystems are predicted to be significant in mountain ecosystems because physiological processes, including rates of carbon (C) cycling, are often more temperature-sensitive in colder environments. Plant biodiversity can also influence C exchange, yet few studies integrate how biotic and abiotic factors may directly or interactively impact ecosystem C flux. Here, we examine the link between simultaneous changes in multiple dimensions of plant diversity and peak growing season ecosystem C uptake across a climatic gradient in the Rocky Mountains, Colorado, USA. We found that taxonomic diversity (species richness), functional diversity (functional evenness), and phylogenetic diversity (mean pairwise distance) were significantly and positively related to peak growing season ecosystem C uptake (i.e., net ecosystem exchange) when considered independently. However, when abiotic and biotic factors were integrated in a structural equation model, only plant phylogenetic diversity was significantly related to C uptake. In addition, we found that actual evapotranspiration (AET-a measure that integrates precipitation and temperature) affected ecosystem C exchange indirectly via its impact on the three dimensions of plant diversity that we examined. These findings highlight complex relationships among key measures of biodiversity and ecosystem C uptake in a rapidly warming ecosystem, and the possible mechanisms that underlie relationships between biodiversity and ecosystem functioning. They also point to the need for integrating multiple dimensions of biodiversity into studies of community and ecosystem ecology.
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  • Prager, Case M., et al. (författare)
  • Integrating natural gradients, experiments, and statistical modeling in a distributed network experiment : An example from the WaRM Network
  • 2022
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 12:10
  • Tidskriftsartikel (refereegranskat)abstract
    • A growing body of work examines the direct and indirect effects of climate change on ecosystems, typically by using manipulative experiments at a single site or performing meta-analyses across many independent experiments. However, results from single-site studies tend to have limited generality. Although meta-analytic approaches can help overcome this by exploring trends across sites, the inherent limitations in combining disparate datasets from independent approaches remain a major challenge. In this paper, we present a globally distributed experimental network that can be used to disentangle the direct and indirect effects of climate change. We discuss how natural gradients, experimental approaches, and statistical techniques can be combined to best inform predictions about responses to climate change, and we present a globally distributed experiment that utilizes natural environmental gradients to better understand long-term community and ecosystem responses to environmental change. The warming and (species) removal in mountains (WaRM) network employs experimental warming and plant species removals at high- and low-elevation sites in a factorial design to examine the combined and relative effects of climatic warming and the loss of dominant species on community structure and ecosystem function, both above- and belowground. The experimental design of the network allows for increasingly common statistical approaches to further elucidate the direct and indirect effects of warming. We argue that combining ecological observations and experiments along gradients is a powerful approach to make stronger predictions of how ecosystems will function in a warming world as species are lost, or gained, in local communities.
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  • Strålin, Kristoffer, et al. (författare)
  • Performance of PCR/electrospray ionization-mass spectrometry on whole blood for detection of bloodstream microorganisms in patients with suspected sepsis
  • 2020
  • Ingår i: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 58:9, s. e01860-19
  • Tidskriftsartikel (refereegranskat)abstract
    • Blood culture (BC) often fails to detect bloodstream microorganisms in sepsis. However, molecular diagnostics hold great potential. The molecular method PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) can detect DNA from hundreds of different microorganisms in whole blood. The aim of the present study was to evaluate the performance of this method in a multicenter study including 16 teaching hospitals in the USA (n=13) and Europe (n=3). First, on 2,754 contrived whole blood samples, with or without spiked microorganisms, PCR/ESI-MS produced 99.1% true positive and 97.2% true negative results. Secondly, among 1,460 patients with suspected sepsis (sepsis-2 definition), BC and PCR/ESI-MS on whole blood were positive in 14.6% and 25.6% of cases, respectively, with the following result combinations: BC+/PCR/ESI-MS-, 4.3%; BC+/PCR/ESI-MS+, 10.3%; BC-/PCR/ESI-MS+, 15.3%; and BC-/PCR/ESI-MS-, 70.1%. Compared with BC, PCR/ESI-MS showed the following sensitivities (coagulase-negative staphylococci not included): Gram-positive bacteria, 58%; Gram-negative bacteria, 78%; and Candida species, 83%. The specificities were > 94% for all individual species. Patients treated with prior antimicrobial medications (n=603) had significantly increased PCR/ESI-MS positivity rates compared with patients without prior antimicrobial treatment, 31% vs 22% (p<0.0001), with pronounced differences for Gram-negative bacteria and Candida species. In conclusion, PCR/ESI-MS showed excellent performance on contrived samples. On clinical samples, it showed high specificities, moderately high sensitivities for Gram-negative bacteria and Candida species, and elevated positivity rates during antimicrobial treatment. These promising results encourage further development of molecular diagnostics on whole blood for detection of bloodstream microorganisms in sepsis.
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  • Sundqvist, Martina, et al. (författare)
  • Barbadin selectively modulates FPR2-mediated neutrophil functions independent of receptor endocytosis
  • 2020
  • Ingår i: Biochimica Et Biophysica Acta-Molecular Cell Research. - : Elsevier BV. - 0167-4889. ; 1867:12
  • Tidskriftsartikel (refereegranskat)abstract
    • FPR2, a member of the family of G protein-coupled receptors (GPCRs), mediates neutrophil migration, a response that has been linked to beta-arrestin recruitment. beta-Arrestin regulates GPCR endocytosis and can also elicit non-canonical receptor signaling. To determine the poorly understood role of beta-arrestin in FPR2 endocytosis and in NADPH-oxidase activation in neutrophils, Barbadin was used as a research tool in this study. Barbadin has been shown to bind the clathrin adaptor protein (AP2) and thereby prevent beta-arrestin/AP2 interaction and beta-arrestin-mediated GPCR endocytosis. In agreement with this, AP2/beta-arrestin interaction induced by an FPR2-specific agonist was inhibited by Barbadin. Unexpectedly, however, Barbadin did not inhibit FPR2 endocytosis, indicating that a mechanism independent of beta-arrestin/AP2 interaction may sustain FPR2 endocytosis. This was confirmed by the fact, that FPR2 also underwent agonist-promoted endocytosis in beta-arrestin deficient cells, albeit at a diminished level as compared to wild type cells. Dissection of the Barbadin effects on FPR2-mediated neutrophil functions including NADPH-oxidase activation mediated release of reactive oxygen species (ROS) and chemotaxis revealed that Barbadin had no effect on chemotactic migration whereas the release of ROS was potentiated/primed. The effect of Barbadin on ROS production was reversible, independent of beta-arrestin recruitment, and similar to that induced by latrunculin A. Taken together, our data demonstrate that endocytic uptake of FPR2 occurs independently of beta-arrestin, while Barbadin selectively augments FPR2-mediated ROS production independently of receptor endocytosis. Given that Barbadin binds to AP2 and prevents the AP2/beta-arrestin interaction, our results indicate a role for AP2 in FPR2-mediated ROS release from neutrophils.
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  • Sundqvist, MO, et al. (författare)
  • Helicobacter Pylori Virulence Factor Cytotoxin-Associated Gene A (CagA) Induces Vascular Calcification in Coronary Artery Smooth Muscle Cells
  • 2023
  • Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Helicobacter pylori (H. pylori) has been associated with cardiovascular diseases. The pro-inflammatory H. pylori virulence factor cytotoxin-associated gene A (CagA) has been detected in serum exosomes of H. pylori-infected subjects and may exert systemic effects throughout the cardiovascular system. The role of H. pylori and CagA in vascular calcification was hitherto unknown. The aim of this study was to determine the vascular effects of CagA through human coronary artery smooth muscle cell (CASMC) osteogenic and pro-inflammatory effector gene expression as well as interleukin 1β secretion and cellular calcification. CagA upregulated bone morphogenic protein 2 (BMP-2) associated with an osteogenic CASMC phenotype switch and induced increased cellular calcification. Furthermore, a pro-inflammatory response was observed. These results support that H. pylori may contribute to vascular calcification through CagA rendering CASMCs osteogenic and inducing calcification.
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  • Tucker, Lori B, et al. (författare)
  • Children with systemic autoinflammatory diseases have multiple, mixed ethnicities that reflect regional ethnic diversity.
  • 2021
  • Ingår i: Clinical and experimental rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 39 Suppl 132:5, s. 124-128
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate the ethnic diversity of children with a systemic autoinflammatory disease (SAID) in a multi-ethnic Canadian province.Self-reported ethnicity of 149 children and adolescents with a SAID in British Columbia, Canada, was analysed for ethnic representation among individual patients, across the cohort, within particular SAIDs, and compared to provincial census data on ethnic diversity.Half of reported cases had a diagnosis of either PFAPA (23.5%) or an unclassifiable autoinflammatory syndrome (31.5%), with a monogenic SAID diagnosed in only 12.8% of cases. The majority of participants (73.1%) were mixed ethnicity with European and Asian heritage reported most frequently (57.0% and 23.0% of all responses, respectively). Ethnic diversity reflected regional diversity except for West Asian, Arabic, Jewish, and Eastern European heritage, which were over-represented in SAID patients, and Chinese descent, which was under-represented in our cohort compared to the general population of British Columbia.Results from this study show extensive multi-ethnic diversity in individual patients and across the various SAIDs inclusive of monogenic SAIDs that are frequently associated with particular ethnicities. Although not disproportionately represented, this is the first report of systemic autoinflammatory disease in Canadian children of Indigenous heritage.
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  • Yang, Jiangning, et al. (författare)
  • Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP
  • 2023
  • Ingår i: Journal of Clinical Investigation. - : American Society For Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:17
  • Tidskriftsartikel (refereegranskat)abstract
    • Red blood cells (RBCs) mediate cardioprotection via nitric oxide-like bioactivity, but the signaling and the identity of any mediator released by the RBCs remains unknown. We investigated whether RBCs exposed to hypoxia release a cardioprotective mediator and explored the nature of this mediator. Perfusion of isolated hearts subjected to ischemia-reperfusion with extracellular supernatant from mouse RBCs exposed to hypoxia resulted in improved postischemic cardiac function and reduced infarct size. Hypoxia increased extracellular export of cyclic guanosine monophosphate (cGMP) from mouse RBCs, and exogenous cGMP mimicked the cardioprotection induced by the supernatant. The protection induced by hypoxic RBCs was dependent on RBC-soluble guanylate cyclase and cGMP transport and was sensitive to phosphodiesterase 5 and activated cardiomyocyte protein kinase G. Oral administration of nitrate to mice to increase nitric oxide bioactivity further enhanced the cardioprotective effect of hypoxic RBCs. In a placebo-controlled clinical trial, a clear cardioprotective, soluble guanylate cyclase-dependent effect was induced by RBCs collected from patients randomized to 5 weeks nitrate-rich diet. It is concluded that RBCs generate and export cGMP as a response to hypoxia, mediating cardioprotection via a paracrine effect. This effect can be further augmented by a simple dietary intervention, suggesting preventive and therapeutic opportunities in ischemic heart disease.
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