SUMMARYIn fishes, performance failure at high temperature is thought to be due to a limitation on oxygen delivery (the theory of oxygen and capacity limited thermal tolerance, OCLTT), which suggests that thermal tolerance and hypoxia tolerance might be functionally associated. Here we examined variation in temperature and hypoxia tolerance among 41 families of Atlantic salmon (Salmo salar), which allowed us to evaluate the association between these two traits. Both temperature and hypoxia tolerance varied significantly among families and there was a significant positive correlation between critical maximum temperature (CT max ) and hypoxia tolerance, supporting the OCLTT concept. At the organ and cellular levels, we also discovered support for the OCLTT concept as relative ventricle mass (RVM) and cardiac myoglobin (Mb) levels both correlated positively with CT max (R 2 =0.21, P<0.001 and R 2 =0.17, P=0.003, respectively). A large RVM has previously been shown to be associated with high cardiac output, which might facilitate tissue oxygen supply during elevated oxygen demand at high temperatures, while Mb facilitates the oxygen transfer from the blood to tissues, especially during hypoxia. The data presented here demonstrate for the first time that RVM and Mb are correlated with increased upper temperature tolerance in fish. High phenotypic variation between families and greater similarity among full-and half-siblings suggests that there is substantial standing genetic variation in thermal and hypoxia tolerance, which could respond to selection either in aquaculture or in response to anthropogenic stressors such as global climate change.

SUMMARYThe objective of this study was to determine whether acclimation to hypoxia and sustained exercise would increase hypoxia tolerance (as indicated by a decrease in critical oxygen tension, P crit ) and swimming performance in goldfish (Carassius auratus), and to investigate the relationship between changes in performance and gill remodelling and tissue metabolic capacity. Goldfish were acclimated to either hypoxia (48h at 0.3mg O 2 l ) and compared with values from control fish. Acclimation to both hypoxia and sustained exercise improved hypoxia tolerance (P crit was reduced by 49% and 39%, respectively), which was associated with an increase in lamellar surface area (71% and 43%, respectively) and an increase in blood [Hb] (26% in both groups). Exercise acclimation also resulted in a decrease in routine M O2 (M O2,rout ). Acclimation to both hypoxia and sustained exercise resulted in a significant increase in U crit in hypoxia (18% and 17%, respectively), which was associated with an increase in maximal O 2 consumption rate at U crit (M O2,active ; 35% and 39%, respectively). While hypoxia acclimation resulted in an increase in U crit in normoxia, acclimation to sustained exercise did not improve subsequent swimming performance in normoxia. This lack of improvement was possibly due to depleted oxidizable substrates during exercise acclimation.

Aging is accompanied by impaired glucose homeostasis and an increased risk of type 2 diabetes, culminating in the failure of insulin secretion from pancreatic β-cells. To investigate the effects of age on β-cell metabolism, we established a novel assay to directly image islet metabolism with NAD(P)H fluorescence lifetime imaging (FLIM). We determined that impaired mitochondrial activity underlies an age-dependent loss of insulin secretion in human islets. NAD(P)H FLIM revealed a comparable decline in mitochondrial function in the pancreatic islets of aged mice (≥24 months), the result of 52% and 57% defects in flux through complex I and II, respectively, of the electron transport chain. However, insulin secretion and glucose tolerance are preserved in aged mouse islets by the heightened metabolic sensitivity of the β-cell triggering pathway, an adaptation clearly encoded in the metabolic and Ca2+ oscillations that trigger insulin release (Ca2+ plateau fraction: young 0.211 ± 0.006, aged 0.380 ± 0.007, P < 0.0001). This enhanced sensitivity is driven by a reduction in KATP channel conductance (diazoxide: young 5.1 ± 0.2 nS; aged 3.5 ± 0.5 nS, P < 0.01), resulting in an ∼2.8 mmol/L left shift in the β-cell glucose threshold. The results demonstrate how mice but not humans are able to successfully compensate for age-associated metabolic dysfunction by adjusting β-cell glucose sensitivity and highlight an essential mechanism for ensuring the maintenance of insulin secretion.

Clumped isotopes (Δ 47) analysis in carbonates is becoming widespread across the geochemical community as a geothermometer that also allows for the reconstruction of the precipitating fluid δ 18 O composition. While initial Δ 47-temperature relationship discrepancies between laboratories have been considerably reduced over the past 10 years, theoretical temperature calibration and laboratory experimental efforts have still not converged to common ground. Moreover, a lack of high temperature anchor points has weakened its application to high temperature calcite formation. Here we present a temperature calibration for carbonate clumped isotopes between 5 and 726°C, using synthetically precipitated and heated calcites, to extend the calcite Δ 47-temperature calibration to higher temperatures. By showing a strong agreement between the empirical calibration proposed here, theoretical and all recently published T-calibrations made using a full carbonate referencing scheme, this study: (1) provides a calibration allowing more precise application in high temperature geological systems, (2) further supports the improvement of inter-laboratory comparison by using carbonate standards, (3) reconciles empirical temperature calibrations with theory.

No abstract