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Sökning: WFRF:(Kenne L.)

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  • Labberton, L, et al. (författare)
  • Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection
  • 2016
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12616-
  • Tidskriftsartikel (refereegranskat)abstract
    • Polyphosphate is an inorganic procoagulant polymer. Here we develop specific inhibitors of polyphosphate and show that this strategy confers thromboprotection in a factor XII-dependent manner. Recombinant Escherichia coli exopolyphosphatase (PPX) specifically degrades polyphosphate, while a PPX variant lacking domains 1 and 2 (PPX_Δ12) binds to the polymer without degrading it. Both PPX and PPX_Δ12 interfere with polyphosphate- but not tissue factor- or nucleic acid-driven thrombin formation. Targeting polyphosphate abolishes procoagulant platelet activity in a factor XII-dependent manner, reduces fibrin accumulation and impedes thrombus formation in blood under flow. PPX and PPX_Δ12 infusions in wild-type mice interfere with arterial thrombosis and protect animals from activated platelet-induced venous thromboembolism without increasing bleeding from injury sites. In contrast, targeting polyphosphate does not provide additional protection from thrombosis in factor XII-deficient animals. Our data provide a proof-of-concept approach for combating thrombotic diseases without increased bleeding risk, indicating that polyphosphate drives thrombosis via factor XII.
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  • Chaillou, Thomas, 1985-, et al. (författare)
  • NDUFA4L2 : Connecting metabolic signals and mitochondrial function in cardiac and skeletal muscle
  • 2016
  • Ingår i: Free Radical Biology & Medicine. - : Elsevier. - 0891-5849 .- 1873-4596. ; 100:Suppl., s. S186-S186
  • Tidskriftsartikel (refereegranskat)abstract
    • The nuclear-encoded mitochondrial protein NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) was recently identified. NDUFAe4L2 is shown to be induced by hypoxia via HIF1α and is thought to inhibit production of mitochondrial reactive oxygen species in fibroblasts exposed to hypoxia. Here the aim was to characterize the role of NDUFA4L2 in the mitochondria-rich tissues skeletal and cardiac muscle. We show hypoxia induced NDUFA4L2 expression in isolated muscle fibers and in cardiomyocytes with full activation after ~3-6 h in hypoxia. The half-maximal O2 level for NDUFA4L2 expression (~4.6 % of ambient O2) suggests sensitivity to changes in O2 tension that occur under physiological conditions (e.g. exercise, moderate ischemia). We identified that the NDUFA4L2 gene promoter has binding sites for transcription factors other than HIF-1α; repetitive sites for PPARα,γ and one for Nrf2. NDUFA4L2 overexpression resulted in functional effects on skeletal and cardiac muscle; e.g. it alters cellular Ca2+ signaling and the expression of Ca2+ handling genes. Further, NDUFA4L2 overexpression reduces muscle mass (~20%), leading to a decreased force production in skeletal muscle. The NDUFA4L2-induced loss of muscle mass was associated with increases in mRNA levels of e.g. MurF1, Mul1, caspase-3 and Bax. Additionally, femoral artery ligation (FAL) induced NDUFA4L2 expression, which correlates with the decreased force production eight days post-FAL in skeletal muscle. Moreover, NDUFA4L2 upregulates antioxidant gene expression and silencing NDUFA4L2 makes cardiac cells less tolerant to hypoxia/re-oxygenation. Our results suggest that NDUFA4L2 expression affects vital functions in muscle cells and at least part of this effect is mediated by a link between NDUFA4L2 and nuclear gene expression. Thus, NDUFA4L2 might act as an integrator of the nutritional, environmental and functional status in muscle cells.
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  • Fredlund, E., et al. (författare)
  • Metabolite profiles of the biocontrol yeast Pichia anomala J121 grown under oxygen limitation
  • 2004
  • Ingår i: Applied Microbiology and Biotechnology. - : Springer. - 0175-7598 .- 1432-0614. ; 64:3, s. 403-409
  • Tidskriftsartikel (refereegranskat)abstract
    • The biocontrol yeast Pichia anomala J121 prevents mould growth during the storage of moist grain under low oxygen/high carbon dioxide conditions. Growth and metabolite formation of P. anomala was analyzed under two conditions of oxygen limitation: (a) initial aerobic conditions with restricted oxygen access during the growth period and (b) initial microaerobic conditions followed by anaerobiosis. Major intra- and extracellular metabolites were analyzed by high-resolution magic-angle spinning (HR-MAS) NMR and HPLC, respectively. HR-MAS NMR allows the analysis of major soluble compounds inside intact cells, without the need for an extraction step. Biomass production was higher in treatment (a), whereas the specific ethanol production rate during growth on glucose was similar in both treatments. This implies that oxygen availability affected the respiration and not the fermentation of the yeast. Following glucose depletion, ethanol was oxidized to acetate in treatment (a), but continued to be produced in (b). Arabitol accumulated in the culture substrate of both treatments, whereas glycerol only accumulated in treatment (b). Trehalose, arabitol, and glycerol accumulated inside the cells in both treatments. The levels of these metabolites were generally significantly higher in treatment (b) than in (a), indicating their importance for P. anomala during severe oxygen limitation/anaerobic conditions.
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  • Harding, SG, et al. (författare)
  • Water transport during the drying of cardboard studied by NMR imaging and diffusion techniques
  • 2001
  • Ingår i: Chemical Engineering Science. - 0009-2509. ; 56:18, s. 5269-5281
  • Tidskriftsartikel (refereegranskat)abstract
    • An understanding of the distribution of water in wood pulp during drying is of fundamental importance to the paper industry. In this study nuclear magnetic resonance (NMR) imaging is used to measure quantitative water profiles during the drying of liquid packaging board with initial water ratio (water: dry mass) of approximately 1.5. The drying was carried out in situ within the magnet, under a range of air temperatures (20-60 degreesC), flow rates (135-400 1 h(-1)) and humidity conditions. One dimensional (1D) slice selective profiles were acquired along the thickness direction of the cardboard with a spatial resolution of 15 mum pixel(-1) at regular time points during the drying process. To give further insight into the distribution of water within the cellulose fibre matrix pulsed gradient spin echo (PGSE) diffusion measurements were acquired on samples equilibrated to water ratios between 0.2 and 2.0. The water profiles show that the initial water concentration varies between the three layers in the composite cardboard. At faster drying conditions the initial water loss is predominantly from the two outer layers, while with slower drying conditions the water loss is more homogeneous throughout all layers. The diffusion coefficient of the fibre water was found to decrease significantly with water content and was slower across the cardboard thickness (thus across the fibres) than parallel to the cardboard surface. (C) 2001 Elsevier Science Ltd. All rights reserved.
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  • Kenne, Ellinor, et al. (författare)
  • Neutrophils engage the kallikrein-kinin system to open up the endothelial barrier in acute inflammation
  • 2019
  • Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - 1530-6860. ; 33:2, s. 2599-2609
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutrophil recruitment and plasma exudation are key elements in the immune response to injury or infection. Activated neutrophils stimulate opening of the endothelial barrier; however, the underlying mechanisms have remained largely unknown. In this study, we identified a pivotal role of the proinflammatory kallikrein-kinin system and consequent formation of bradykinin in neutrophil-evoked vascular leak. In mouse and hamster models of acute inflammation, inhibitors of bradykinin generation, and signaling markedly reduced plasma exudation in response to chemoattractant activation of neutrophils. The neutrophil-driven leak was likewise suppressed in mice deficient in either the bradykinin B2 receptor or factor XII (initiator of the kallikrein-kinin system). In human endothelial cell monolayers, material secreted from activated neutrophils induced cytoskeletal rearrangement, leading to paracellular gap formation in a bradykinin-dependent manner. As a mechanistic basis, we found that a neutrophil-derived heparin-binding protein (HBP/azurocidin) displaced the bradykinin precursor high-molecular-weight kininogen from endothelial cells, thereby enabling proteolytic processing of kininogen into bradykinin by neutrophil and plasma proteases. These data provide novel insight into the signaling pathway by which neutrophils open up the endothelial barrier and identify the kallikrein-kinin system as a target for therapeutic interventions in acute inflammatory reactions.-Kenne, E., Rasmuson, J., Renné, T., Vieira, M. L., Müller-Esterl, W., Herwald, H., Lindbom, L. Neutrophils engage the kallikrein-kinin system to open up the endothelial barrier in acute inflammation.
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  • Liu, Zhengye, et al. (författare)
  • Mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force
  • 2021
  • Ingår i: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 35:12
  • Tidskriftsartikel (refereegranskat)abstract
    • The hypoxia-inducible nuclear-encoded mitochondrial protein NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) has been demonstrated to decrease oxidative phosphorylation and production of reactive oxygen species in neonatal cardiomyocytes, brain tissue and hypoxic domains of cancer cells. Prolonged local hypoxia can negatively affect skeletal muscle size and tissue oxidative capacity. Although skeletal muscle is a mitochondrial rich, oxygen sensitive tissue, the role of NDUFA4L2 in skeletal muscle has not previously been investigated. Here we ectopically expressed NDUFA4L2 in mouse skeletal muscles using adenovirus-mediated expression and in vivo electroporation. Moreover, femoral artery ligation (FAL) was used as a model of peripheral vascular disease to induce hind limb ischemia and muscle damage. Ectopic NDUFA4L2 expression resulted in reduced mitochondrial respiration and reactive oxygen species followed by lowered AMP, ADP, ATP, and NAD(+) levels without affecting the overall protein content of the mitochondrial electron transport chain. Furthermore, ec-topically expressed NDUFA4L2 caused a similar to 20% reduction in muscle mass that resulted in weaker muscles. The loss of muscle mass was associated with increased gene expression of atrogenes MurF1 and Mul1, and apoptotic genes caspase 3 and Bax. Finally, we showed that NDUFA4L2 was induced by FAL and that the Ndufa4l2 mRNA expression correlated with the reduced capacity of the muscle to generate force after the ischemic insult. These results show, for the first time, that mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force. Specifically, induced NDUFA4L2 reduces mitochondrial activity leading to lower levels of important intramuscular metabolites, including adenine nucleotides and NAD(+), which are hallmarks of mitochondrial dysfunction and hence shows that dysfunctional mitochondrial activity may drive muscle wasting.
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  • Sundberg, K., et al. (författare)
  • The sense of coherence scale in a clinical nursing perspective: A scoping review
  • 2022
  • Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 31:11-12, s. 1428-1439
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The concept of sense of coherence explains a person's resources to maintain health during times of considerable strain and is suggested to be applicable in nursing. A summary of how it has been applied and adapted in clinical nursing is warranted for further conceptual development and research. Objective The scoping review aimed to explore how the sense of coherence scale has been used from a clinical nursing research perspective. Method Published articles (N = 2812) through December 2018 were identified in the PubMed, Cinahl and PsychInfo databases. A total of 298 articles were included in the review. A five-stage process was used to extract data based on pre-determined selection criteria. Summative content analysis was used for the categorisation of the data. The PRISMA-ScR checklist was chosen. Results A majority of the articles were published within the Nordic countries and the short version SOC-13 was the most frequently used scale. Most studies stated the significant relationship of a higher sense of coherence and higher emotional and psychosocial well-being, quality of life, and well-being irrespective of condition. Other articles proposed identifying patients' degree of sense of coherence either to individualise care or to plan an intervention to strengthen sense of coherence. Conclusions The sense of coherence scale has been widely used within nursing and identified as an important factor to individualise care. Future research should focus on rigorous intervention studies to determine if recognising patients' degree of sense of coherence in clinical nursing enables tailored care for patients when dealing with a disease-related condition. More evidence is needed when seeking to improve sense of coherence. Relevance to clinical practice These results show an expansion of the concept of sense of coherence and endorses its use in nursing care for identifying patients' needs in the process of presenting individualised care.
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  • Unnithan, VB, et al. (författare)
  • The effect of partial body weight support on the oxygen cost of walking in children and adolescents with spastic cerebral palsy
  • 2006
  • Ingår i: PEDIATRIC EXERCISE SCIENCE. - : Human Kinetics. - 0899-8493 .- 1543-2920. ; 18:1, s. 11-21
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this study was to assess the effect of partial body weight support on the oxygen cost of treadmill walking in children and adolescents with spastic cerebral palsy (CP). Five children and adolescents (2 girls and 3 boys) with spastic CP (12.4 ± 3.6 years) volunteered for the study. Participants performed three 4-min tread mill walks on three separate days at their comfortable treadmill walking speeds. At each visit a different partial body weight harness setting was used. Significant (p < .05) differences in oxygen cost were found when the harness was worn but not connected to the support frame. Partial body weight support reduces the oxygen cost of walking in children and adolescents with spastic CP.
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  • Wimo, Anders, et al. (författare)
  • The worldwide costs of dementia in 2019
  • 2023
  • Ingår i: Alzheimer's & Dementia. - : WILEY. - 1552-5260 .- 1552-5279. ; 19:7, s. 2865-2873
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Dementia is a leading cause of death and disability globally. Estimating total societal costs demonstrates the wide impact of dementia and its main direct and indirect economic components.Methods: We constructed a global cost model for dementia, presenting costs as cumulated global and regional costs.Results: In 2019, the annual global societal costs of dementia were estimated at US $1313.4 billion for 55.2 million people with dementia, corresponding to US $23,796 per person with dementia. Of the total, US $213.2 billion (16%) were direct medical costs, US $448.7 billion (34%) direct social sector costs (including long-term care), and US $651.4 billion (50%) costs of informal care.Discussion: The huge costs of dementia worldwide place enormous strains on care systems and families alike. Although most people with dementia live in low- and middle-income countries, highest total and per-person costs are seen in high-income countries.
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