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- Brutsaert, T. D., et al.
(författare)
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Larger spleens and greater splenic contraction during exercise may be an adaptive characteristic of Nepali Sherpa at high-altitude
- 2024
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Ingår i: American Journal of Human Biology. - : Wiley. - 1042-0533 .- 1520-6300.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The Sherpa ethnic group living at altitude in Nepal may have experienced natural selection in response to chronic hypoxia. We have previously shown that Sherpa in Kathmandu (1400 m) possess larger spleens and a greater apnea-induced splenic contraction compared to lowland Nepalis. This may be significant for exercise capacity at altitude as the human spleen responds to stress-induced catecholamine secretion by an immediate contraction, which results in transiently elevated hemoglobin concentration ([Hb]). Methods: To investigate splenic contraction in response to exercise at high-altitude (4300 m; Pb = ~450 Torr), we recruited 63 acclimatized Sherpa (29F) and 14 Nepali non-Sherpa (7F). Spleen volume was measured before and after maximal exercise on a cycle ergometer by ultrasonography, along with [Hb] and oxygen saturation (SpO2). Results: Resting spleen volume was larger in the Sherpa compared with Nepali non-Sherpa (237 ± 62 vs. 165 ± 34 mL, p <.001), as was the exercise-induced splenic contraction (Δspleen volume, 91 ± 40 vs. 38 ± 32 mL, p <.001). From rest to exercise, [Hb] increased (1.2 to 1.4 g.dl−1), SpO2 decreased (~9%) and calculated arterial oxygen content (CaO2) remained stable, but there were no significant differences between groups. In Sherpa, both resting spleen volume and the Δspleen volume were modest positive predictors of the change (Δ) in [Hb] and CaO2 with exercise (p-values from.026 to.037 and R2 values from 0.059 to 0.067 for the predictor variable). Conclusions: Larger spleens and greater splenic contraction may be an adaptive characteristic of Nepali Sherpa to increase CaO2 during exercise at altitude, but the direct link between spleen size/function and hypoxia tolerance remains unclear.
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- Delios, A., et al.
(författare)
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Examining the generalizability of research findings from archival data
- 2022
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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. - 0027-8424 .- 1091-6490. ; 119:30
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Tidskriftsartikel (refereegranskat)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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- Holmström, Pontus K., et al.
(författare)
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Differential splenic responses to hyperoxic breathing at high altitude in Sherpa and lowlanders
- 2024
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 109:4, s. 535-548
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Tidskriftsartikel (refereegranskat)abstract
- The human spleen contracts in response to stress-induced catecholamine secretion, resulting in a temporary rise in haemoglobin concentration ([Hb]). Recent findings highlighted enhanced splenic response to exercise at high altitude in Sherpa, possibly due to a blunted splenic response to hypoxia. To explore the potential blunted splenic contraction in Sherpas at high altitude, we examined changes in spleen volume during hyperoxic breathing, comparing acclimatized Sherpa with acclimatized individuals of lowland ancestry. Our study included 14 non-Sherpa (7 female) residing at altitude for a mean continuous duration of 3 months and 46 Sherpa (24 female) with an average of 4 years altitude exposure. Participants underwent a hyperoxic breathing test at altitude (4300 m; barrometric pressure = ∼430 torr; (Formula presented.) = ∼90 torr). Throughout the test, we measured spleen volume using ultrasonography and monitored oxygen saturation ((Formula presented.)). During rest, Sherpa exhibited larger spleens (226 ± 70 mL) compared to non-Sherpa (165 ± 34 mL; P < 0.001; effect size (ES) = 0.95, 95% CI: 0.3–1.6). In response to hyperoxia, non-Sherpa demonstrated 22 ± 12% increase in spleen size (35 ± 17 mL, 95% CI: 20.7–48.9; P < 0.001; ES = 1.8, 95% CI: 0.93–2.66), while spleen size remained unchanged in Sherpa (−2 ± 13 mL, 95% CI: −2.4 to 7.3; P = 0.640; ES = 0.18, 95% CI: −0.10 to 0.47). Our findings suggest that Sherpa and non-Sherpas of lowland ancestry exhibit distinct variations in spleen volume during hyperoxia at high altitude, potentially indicating two distinct splenic functions. In Sherpa, this phenomenon may signify a diminished splenic response to altitude-related hypoxia at rest, potentially contributing to enhanced splenic contractions during physical stress. Conversely, non-Sherpa experienced a transient increase in spleen size during hyperoxia, indicating an active tonic contraction, which may influence early altitude acclimatization in lowlanders by raising [Hb].
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- El-Semman, Ibrahim, 1977, et al.
(författare)
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Whole-cell modeling in yeast predicts compartment-specific proteome constraints that drive metabolic strategies
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- When conditions change, unicellular organisms rewire their metabolism to sustain cell maintenance and cellular growth. Such rewiring may be understood as resource re-allocation under cellular constraints. Eukaryal cells contain metabolically active organelles such as mitochondria, competing for cytosolic space and resources, and the nature of the relevant cellular constraints remain to be determined for such cells. Here, we present a comprehensive metabolic model of the yeast cell, based on its full metabolic reaction network extended with protein synthesis and degradation reactions. The model predicts metabolic fluxes and corresponding protein expression by constraining compartment-specific protein pools and maximising growth rate. Comparing model predictions with quantitative experimental data suggests that under glucose limitation, a mitochondrial constraint limits growth at the onset of ethanol formation-known as the Crabtree effect. Under sugar excess, however, a constraint on total cytosolic volume dictates overflow metabolism. Our comprehensive model thus identifies condition-dependent and compartment-specific constraints that can explain metabolic strategies and protein expression profiles from growth rate optimisation, providing a framework to understand metabolic adaptation in eukaryal cells.
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