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Sökning: WFRF:(Eriksson Mikael) > (2020-2021)

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1.
  • Molin, Mikael, 1973, et al. (författare)
  • Protein kinase A controls yeast growth in visible light
  • 2020
  • Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A wide variety of photosynthetic and non-photosynthetic species sense and respond to light, having developed protective mechanisms to adapt to damaging effects on DNA and proteins. While the biology of UV light-induced damage has been well studied, cellular responses to stress from visible light (400–700 nm) remain poorly understood despite being a regular part of the life cycle of many organisms. Here, we developed a high-throughput method for measuring growth under visible light stress and used it to screen for light sensitivity in the yeast gene deletion collection. Results: We found genes involved in HOG pathway signaling, RNA polymerase II transcription, translation, diphthamide modifications of the translational elongation factor eEF2, and the oxidative stress response to be required for light resistance. Reduced nuclear localization of the transcription factor Msn2 and lower glycogen accumulation indicated higher protein kinase A (cAMP-dependent protein kinase, PKA) activity in many light-sensitive gene deletion strains. We therefore used an ectopic fluorescent PKA reporter and mutants with constitutively altered PKA activity to show that repression of PKA is essential for resistance to visible light. Conclusion: We conclude that yeast photobiology is multifaceted and that protein kinase A plays a key role in the ability of cells to grow upon visible light exposure. We propose that visible light impacts on the biology and evolution of many non-photosynthetic organisms and have practical implications for how organisms are studied in the laboratory, with or without illumination.
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2.
  • Engström, Jens, et al. (författare)
  • Energy absorption from parks of point-absorbing wave energy converters in the Swedish exclusive economic zone
  • 2020
  • Ingår i: Energy Science & Engineering. - : John Wiley & Sons. - 2050-0505. ; 8:1, s. 38-49
  • Tidskriftsartikel (refereegranskat)abstract
    • In a future energy system based on renewable energy sources, wave energy will most likely play a role due to its high energy potential and low intermittency. The power production from parks of wave energy converters of point absorber type has been extensively studied. This is also the case for the wave energy resource at many coastal areas around the globe. Wave energy has not yet reached a commercial level, and a large variety of technologies exist; therefore, an established method to calculate the technical potential for wave energy has still not been established. To estimate the technical potential of wave energy conversion, some approximations inevitably need to be taken due to the systems high complexity. In this study, a detailed mapping of the wave climate and simulation of large arrays of hydrodynamically cross‐coupled wave energy converters are combined to calculate the technical potential for wave energy conversion in the Swedish exclusive economic zone. A 16‐year wave data set distributed in a 1.1 km × 1.1 km grid is used to calculate the absorbed energy from a park of 200 generic point absorbers. The areas with best potential have an average annual energy absorption of 16 GWh for the selected wave energy park adapted to 1 km2 when using a constant damping, while the theoretical upper bound is 63 GWh for the same area.
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3.
  • Gabrielson, Marike, et al. (författare)
  • Inclusion of Endogenous Plasma Dehydroepiandrosterone Sulfate and Mammographic Density in Risk Prediction Models for Breast Cancer
  • 2020
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 29:3, s. 574-581
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Endogenous hormones and mammographic density are risk factors for breast cancer. Joint analyses of the two may improve the ability to identify high-risk women.Methods: This study within the KARMA cohort included pre-diagnostic measures of plasma hormone levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and mammographic density in 629 cases and 1,223 controls, not using menopausal hormones. We evaluated the area under the receiver-operating curve (AUC) for risk of breast cancer by adding DHEA, DHEAS, and mammographic density to the Gail or Tyrer-Cuzick 5-year risk scores or the CAD2Y 2-year risk score.Results: DHEAS and percentage density were independently and positively associated with breast cancer risk (P = 0.007 and P < 0.001, respectively) for postmenopausal, but not premenopausal, women. No significant association was seen for DHEA. In postmenopausal women, those in the highest tertiles of both DHEAS and density were at greatest risk of breast cancer (OR, 3.5; 95% confidence interval, 1.9-6.3) compared with the lowest tertiles. Adding DHEAS significantly improved the AUC for the Gail (+2.1 units, P = 0.008) and Tyrer-Cuzick (+1.3 units, P = 0.007) risk models. Adding DHEAS to the Gail and Tyrer-Cuzick models already including mammographic density further increased the AUC by 1.2 units (P = 0.006) and 0.4 units (P = 0.007), respectively, compared with only including density.Conclusions: DHEAS and mammographic density are independent risk factors for breast cancer and improve risk discrimination for postmenopausal breast cancer.Impact: Combining DHEAS and mammographic density could help identify women at high risk who may benefit from individualized breast cancer screening and/or preventive measures among postmenopausal women.
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5.
  • Klaric, Lucija, et al. (författare)
  • Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
  • 2021
  • Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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7.
  • Ashman Kröönström, Linda, 1982, et al. (författare)
  • Exercise capacity, physical activity, and health-related quality of life in adults with CHD
  • 2020
  • Ingår i: Cardiology in the Young. - 1047-9511 .- 1467-1107. ; 30:5, s. 668-673
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim of this study was to assess exercise capacity, physical activity, and health-related quality of life within a broad and unselected group of adults with CHD.Design: From April 2009 to February 2014, 1310 patients were assessed for suitability to participate in this single-centre cross-sectional study. Seven hundred and forty-seven (57%) patients were included, performed a submaximal bicycle test, and answered questionnaires regarding physical activity and health-related quality of life. Exercise capacity, physical activity, and health-related quality of life were compared with reference values and correlations were studied.Results: The exercise capacities of men and women with CHD were 58.7 and 66.3%, respectively, of reference values. Approximately, 20-25% of the patients did not achieve the recommended amount of physical activity. In addition, men scored significantly less points on 7 out of 10 scales of health-related quality of life and women in 6 out of 10 scales, compared with reference values. The strongest correlation was between exercise capacity and the Short Form-36 (physical function).Conclusions: Exercise capacity was impaired in all adults with CHD, including those with less complicated CHD. One-quarter of the patients did not achieve the recommended levels of physical activity. Exercise tests followed by individualised exercise prescriptions may be offered to all patients with CHD aiming to increase exercise capacity, levels of physical activity, improve health-related quality of life, and reduce the risk of acquired life-style diseases.
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9.
  • Ashman Kröönström, Linda, 1982, et al. (författare)
  • Post-operative musculoskeletal outcomes in patients with coarctation of the aorta following different surgical approaches.
  • 2021
  • Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 327, s. 80-85
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to examine range of motion and muscle function in the upper extremity and spine in patients with coarctation of the aorta (CoA) comparing different surgical approaches.From October 2017 to February 2019, 150 patients were assessed for inclusion. A total of 99 patients (n = 75 CoA, n = 24 control), were included and assessed regarding muscle function, arm length and circumference, and spinal and thoracic mobility.There were significant differences between the right and left arm in patients with CoA, operated with the subclavian flap technique compared to controls in regards to shoulder flexion (p < 0.001), elbow flexion (p = 0.001), shoulder abduction (p = 0.02), handgrip strength (p = 0.01), length of upper arm (p < 0.001), lower arm (p < 0.001), and of whole arm (p < 0.001), circumference regarding upper arm (p = 0.001), lower arm (p < 0.001), and wrist (p < 0.001). Structural scoliosis was more frequent in patients who had undergone thoracotomy (25.4%) than patients who had not undergone a thoracotomy (5.9%, p = 0.04), and were often located in the thoracic part of the spine.Patients with CoA operated on using the subclavian flap technique have impaired muscle function as well as reduced arm length and circumference. An increased rate of structural scoliosis was found in patients who underwent thoracotomy, in comparison with patients who had not undergone a thoracotomy. Further research is needed to determine whether muscle function impaired by surgical procedures can be improved with exercise.
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