| 91. |
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| 92. |
- Larsen, M. H., et al.
(författare)
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Reduced rearing density increases postrelease migration success of Atlantic salmon (Salmo salar) smolts
- 2016
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Ingår i: Canadian Journal of Fisheries and Aquatic Sciences. - : Canadian Science Publishing. - 0706-652X .- 1205-7533. ; 73:5, s. 804-810
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Tidskriftsartikel (refereegranskat)abstract
- The overall aim of this study was to investigate the effect of rearing density on the postrelease survival of Atlantic salmon (Salmo salar) smolts during seaward migration. Fish were either reared at conventional hatchery density or at one-third of conventional density. Three hundred 1-year-old smolts from each density treatment were individually tagged with passive integrated transponder tags and released 3.2 km upstream of a stationary antenna array in a natural stream. There were no significant differences in length, body mass, or condition between fish from the two density treatments during rearing in the hatchery. However, individuals reared at reduced density had less eroded dorsal fins and opercula relative to those from the high-density treatment. In the stream, the downstream migration success was 16% higher for fish reared at reduced density than for conspecifics kept at high density, but the timing of migration was similar for both groups. These novel results suggest that conventionally high rearing densities may reduce welfare and the postrelease migration success of hatchery-reared Atlantic salmon.
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| 93. |
- Le Guen, Yann, et al.
(författare)
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Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
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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 (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
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Tidskriftsartikel (refereegranskat)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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| 94. |
- Leiros, H. K. S., et al.
(författare)
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Structural insights into the enhanced carbapenemase efficiency of OXA-655 compared to OXA-10
- 2020
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Ingår i: FEBS Open Bio. - : Wiley. - 2211-5463. ; 10:9, s. 1821-1832
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Tidskriftsartikel (refereegranskat)abstract
- Carbapenemases are the main cause of carbapenem resistance in Gram-negative bacteria. How beta-lactamases with weak carbapenemase activity, such as the OXA-10-type class D beta-lactamases, contribute to anti-bacterial drug resistance is unclear. OXA-655 is a T26M and V117L OXA-10 variant, recently identified from hospital wastewater. Despite exhibiting stronger carbapenemase activity towards ertapenem (ETP) and meropenem (MEM) inEscherichia coli, OXA-655 exhibits reduced activity towards oxyimino-substituted beta-lactams like ceftazidime. Here, we have solved crystal structures of OXA-10 in complex with imipenem (IPM) and ETP, and OXA-655 in complex with MEM in order to unravel the structure-function relationship and the impact of residue 117 in enzyme catalysis. The new crystal structures show that L117 is situated at a critical position with enhanced Van der Waals interactions to L155 in the omega loop. This restricts the movements of L155 and could explain the reduced ability for OXA-655 to bind a bulky oxyimino group. The V117L replacement in OXA-655 makes the active site S67 and the carboxylated K70 more water exposed. This could affect the supply of new deacylation water molecules required for hydrolysis and possibly the carboxylation rate of K70. But most importantly, L117 leaves more space for binding of the hydroxyethyl group in carbapenems. In summary, the crystal structures highlight the importance of residue 117 in OXA-10 variants for carbapenemase activity. This study also illustrates the impact of a single amino acid substitution on the substrate profile of OXA-10 and the evolutionary potential of new OXA-10 variants.
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| 95. |
- Luo, Jiao, et al.
(författare)
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Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease
- 2023
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022.EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors.RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]).CONCLUSIONS AND RELEVANCE This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.
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| 96. |
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| 97. |
- Mohr, Magni, 1973, et al.
(författare)
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Muscle variables of importance for physiological performance in competitive football
- 2016
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 116:2, s. 251-262
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To examine how match performance parameters in trained footballers relate to skeletal muscle parameters, sprint ability and intermittent exercise performance. Methods 19 male elite football players completed an experimental game with physical performance determined by video analysis and exercise capacity assessed by intermittent Yo-Yo IR1 and IR2 tests, and a repeated sprint test (RST). Muscle tissue was obtained for analysis of metabolic enzyme maximal activity and key muscle protein expression. Results Total game distance, distance deficit from first to second half and high-intensity running in the final 15 min of the game were all correlated to the players’ Yo-Yo IR1 performance (r = 0.55–0.87) and beta-hydroxyacyl-CoA-dehydrogenase (HAD) maximal activity (r = 0.55–0.65). Furthermore, platelet/endothelial cell adhesion molecule-1 (PECAM1) protein expression was weakly (r = 0.46) correlated to total game distance. Peak 5-min game distance faster than 21 km h−1 was related to the Na+–K+ ATPase subunit (α1, α2, β1 and FXYD1) protein levels (r = 0.54–0.70), while Yo-Yo IR2 performance explained 40 % of the variance in high-intensity game distance. Total and 1-min peak sprint distance correlated to myosin heavy chain II/I ratio (MHCII/I ratio) and sarcoendoplasmic reticulum Ca2+ ATPase isoform-1 (SERCA1) protein (r = 0.56–0.86), while phosphofructokinase (PFK) maximal activity also correlated to total sprint distance (r = 0.46). Conclusion The findings emphasize the complexity of parameters predicting physical football performance with Yo-Yo IR1 and HAD as the best predictors of total distance, while high expression of Na+–K+ ATPase proteins and the Yo-Yo IR2 test are better predictors of high-intensity performance. Finally, sprint performance relates to skeletal muscle fiber-type composition.
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| 98. |
- Näslund, Joacim, 1985, et al.
(författare)
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Environment-dependent plasticity and ontogenetic changes in the brain of hatchery-reared Atlantic salmon
- 2017
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Ingår i: Journal of Zoology. - : Wiley. - 0952-8369 .- 1469-7998. ; 301:1, s. 75-82
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Tidskriftsartikel (refereegranskat)abstract
- Lowered rearing density has repeatedly been shown to increase the performance of hatchery-reared salmonids stocked into natural environments. One possible mechanism for this pattern could be that lower densities enhance brain development, which has been shown to be the case in other hatchery enhancement strategies, like environmental enrichment. Here, we investigated the size of the brain in hatchery-reared Atlantic salmon Salmo salar kept at standard (high) and reduced (low) tank densities. In contrast to our predictions, we found that fish reared at high density had larger dry mass of cerebellum and telencephalon, correcting for body size. No differences were detected for total brain mass. Furthermore, we found that the relative size of both telencephalon and cerebellum, in relation to total brain mass, changed with body size. Cerebellum increased in relative size with increased body size, while the opposite pattern was observed for telencephalon. Overall, these results reveal substantial brain plasticity depending on the surrounding environment as well as ontogenetic adaptive changes in the brain of the Atlantic salmon.
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| 99. |
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| 100. |
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