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| 2. |
- Haythorne, E., et al.
(författare)
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Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic beta-cells
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes is a global health problem caused primarily by the inability of pancreatic beta-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of beta-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic beta V59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 beta-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in beta-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of beta-cells in diabetes.
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| 3. |
- Pellissier, V., et al.
(författare)
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Effects of Natura 2000 on nontarget bird and butterfly species based on citizen science data
- 2020
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Ingår i: Conservation Biology. - : Wiley. - 0888-8892 .- 1523-1739. ; 34:3, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- The European Union's Natura 2000 (N2000) is among the largest international networks of protected areas. One of its aims is to secure the status of a predetermined set of (targeted) bird and butterfly species. However, nontarget species may also benefit from N2000. We evaluated how the terrestrial component of this network affects the abundance of nontargeted, more common bird and butterfly species based on data from long-term volunteer-based monitoring programs in 9602 sites for birds and 2001 sites for butterflies. In almost half of the 155 bird species assessed, and particularly among woodland specialists, abundance increased (slope estimates ranged from 0.101 [SD 0.042] to 3.51 [SD 1.30]) as the proportion of landscape covered by N2000 sites increased. This positive relationship existed for 27 of the 104 butterfly species (estimates ranged from 0.382 [SD 0.163] to 4.28 [SD 0.768]), although most butterflies were generalists. For most species, when land-cover covariates were accounted for these positive relationships were not evident, meaning land cover may be a determinant of positive effects of the N2000 network. The increase in abundance as N2000 coverage increased correlated with the specialization index for birds, but not for butterflies. Although the N2000 network supports high abundance of a large spectrum of species, the low number of specialist butterflies with a positive association with the N2000 network shows the need to improve the habitat quality of N2000 sites that could harbor open-land butterfly specialists. For a better understanding of the processes involved, we advocate for standardized collection of data at N2000 sites.
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- Gagliardi, A. R., et al.
(författare)
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The Clinician Guideline Determinants Questionnaire was developed and validated to support tailored implementation planning
- 2019
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356. ; 113, s. 129-136
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this research was to generate and validate a questionnaire that identifies determinants of guideline use from the clinician perspective. Study Design and Setting: From January 2017 to March 2018, a seven-member six-country multidisciplinary team used a five-step multimethod design to search for and compile determinant frameworks, map items to determinants (content validity), select the best items for each determinant (content validity), refine wording of determinants and items (face validity), merge or separate items (construct validity), and review the final questionnaire. Results: The Clinician Guideline Determinants Questionnaire includes four sections: clinician demographic information (including two determinants: attitudes about/experience with guidelines), 26 close-ended items reflecting clinician- and guideline-specific determinants, four open-ended items reflecting enablers and barriers perceived as most important, and three items on learning style (preferred sources of guideline information). Conclusion: The Clinician Guideline Determinants Questionnaire is a comprehensive, validated instrument that addresses multiple potential determinants specific to guideline use from a clinician perspective. The Questionnaire can be used at multiple time points in the guideline development cycle to assess determinants of the use of new, updated, or adapted guidelines and before and after interventions to assess their impact on the determinants of guideline use. In future research, we will establish psychometric properties of the new questionnaire. © 2019 The Authors
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| 5. |
- Zoback, Mary Lou, et al.
(författare)
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Global patterns of tectonic stress
- 1989
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 341:6240, s. 291-298
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Forskningsöversikt (refereegranskat)abstract
- Regional patterns of present-day tectonic stress can be used to evaluate the forces acting on the lithosphere and to investigate intraplate seismicity. Most intraplate regions are characterized by a compressional stress regime; extension is limited almost entirely to thermally uplifted regions. In several plates the maximum horizontal stress is subparallel to the direction of absolute plate motion, suggesting that the forces driving the plates also dominate the stress distribution in the plate interior.
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| 6. |
- Knudsen, J. G., et al.
(författare)
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Dysregulation of Glucagon Secretion by Hyperglycemia-Induced Sodium-Dependent Reduction of ATP Production
- 2019
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 29:2
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes is a bihormonal disorder resulting from combined insulin and glucagon secretion defects. Mice lacking fumarase (Fh1) in their beta cells (Fh1 beta KO mice) develop progressive hyperglycemia and dysregulated glucagon secretion similar to that seen in diabetic patients (too much at high glucose and too little at low glucose). The glucagon secretion defects are corrected by low concentrations of tolbutamide and prevented by the sodium-glucose transport (SGLT) inhibitor phlorizin. These data link hyperglycemia, intracellular Na+ accumulation, and acidification to impaired mitochondrial metabolism, reduced ATP production, and dysregulated glucagon secretion. Protein succination, reflecting reduced activity of fumarase, is observed in alpha cells from hyperglycemic Fh1 beta KO and beta-V59M gain-of-function K-ATP channel mice, diabetic Goto-Kakizaki rats, and patients with type 2 diabetes. Succination is also observed in renal tubular cells and cardiomyocytes from hyperglycemic Fh1 beta KO mice, suggesting that the model can be extended to other SGLT-expressing cells and may explain part of the spectrum of diabetic complications.
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| 8. |
- Teufel, Felix, et al.
(författare)
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Analysis of Attained Height and Diabetes Among 554,122 Adults Across 25 Low- and Middle-Income Countries
- 2020
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:10, s. 2403-2410
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The prevalence of type 2 diabetes is rising rapidly in low-income and middle-income countries (LMICs), but the factors driving this rapid increase are not well understood. Adult height, in particular shorter height, has been suggested to contribute to the pathophysiology and epidemiology of diabetes and may inform how adverse environmental conditions in early life affect diabetes risk. We therefore systematically analyzed the association of adult height and diabetes across LMICs, where such conditions are prominent.RESEARCH DESIGN AND METHODS: We pooled individual-level data from nationally representative surveys in LMICs that included anthropometric measurements and diabetes biomarkers. We calculated odds ratios (ORs) for the relationship between attained adult height and diabetes using multilevel mixed-effects logistic regression models. We estimated ORs for the pooled sample, major world regions, and individual countries, in addition to stratifying all analyses by sex. We examined heterogeneity by individual-level characteristics.RESULTS: Our sample included 554,122 individuals across 25 population-based surveys. Average height was 161.7 cm (95% CI 161.2-162.3), and the crude prevalence of diabetes was 7.5% (95% CI 6.9-8.2). We found no relationship between adult height and diabetes across LMICs globally or in most world regions. When stratifying our sample by country and sex, we found an inverse association between adult height and diabetes in 5% of analyses (2 out of 50). Results were robust to alternative model specifications.CONCLUSIONS: Adult height is not associated with diabetes across LMICs. Environmental factors in early life reflected in attained adult height likely differ from those predisposing individuals for diabetes.
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| 10. |
- Ferreira, S., et al.
(författare)
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Life satisfaction and air quality in Europe
- 2013
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Ingår i: Ecological Economics. - : Elsevier BV. - 0921-8009. ; 88, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Concerns for environmental quality and its impact on people's welfare are fundamental arguments for the adoption of environmental legislation in most countries. In this paper, we analyze the relationship between air quality and subjective well-being in Europe. We use a unique dataset that merges three waves of the European Social Survey with a new dataset on environmental quality including SO2 concentrations and climate in Europe at the regional level. We find a robust negative impact of SO2 concentrations on self-reported life satisfaction.
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