Glycogenin activity and mRNA expression in response to volitional exhaustion in human skeletal muscle.

Glycogenolysis results in the selective catabolism of individual glycogen granules by glycogen phosphorylase. However, once the carbohydrate portion of the granule is metabolized, the fate of glycogenin, the protein primer of granule formation, is not known. To examine this, male subjects (n = 6) exercised to volitional exhaustion (Exh) on a cycle ergometer at 75% maximal O2 uptake. Muscle biopsies were obtained at rest, 30 min, and Exh (99 +/- 10 min). At rest, total glycogen concentration was 497 +/- 41 and declined to 378 +/- 51 mmol glucosyl units/kg dry wt following 30 min of exercise (P < 0.05). There were no significant changes in proglycogen, macroglycogen, glycogenin activity, or mRNA in this period (P > or = 0.05). Exh resulted in decreases in total glycogen, proglycogen, and macroglycogen as well as glycogenin activity (P < 0.05). These decrements were associated with a 1.9 +/- 0.4-fold increase in glycogenin mRNA over resting values (P < 0.05). Glycogenolysis in the initial exercise period (0-30 min) was not adequate to induce changes in glycogenin; however, later in exercise when concentration and granule number decreased further, decrements in glycogenin activity and increases in glycogenin mRNA were demonstrated. Results show that glycogenin becomes inactivated with glycogen catabolism and that this event coincides with an increase in glycogenin gene expression as exercise and glycogenolysis progress.     

Cases Concerning Sovereignty over Islands before the International Court of Justice and the Dokdo/Takeshima Issue

The article analyzes the recent jurisprudence of the International Court of Justice in relation to disputes concerning sovereignty over islands and considers the potential implications of this jurisprudence for the resolution of the Dokdo/Takeshima issue. It does so by examining the principles and rules of international law applied by the Court to the determination of title to territory, especially those concerning the question of original title and its interplay with state conduct in general (effectivités). The article also pays special attention to the different legal techniques applied by the Court in resolving each particular dispute and the Court's practical approach to dealing with questions of historical facts and other evidentiary matters in relation to small and uninhabited islands.     

Speed it up: How temperature drives toxicokinetics of organic contaminants in freshwater amphipods

The acceleration of global climate change draws increasing attention towards interactive effects of temperature and organic contaminants. Many studies reported a higher sensitivity of aquatic invertebrates towards contaminant exposure with increasing or fluctuating temperatures. The hypothesis of this study was that the higher sensitivity of invertebrates is associated with the changes of toxicokinetic processes that determine internal concentrations of contaminants and consequently toxic effects. Therefore, the influence of temperature on toxicokinetic processes and the underlying mechanisms were studied in two key amphipod species (Gammarus pulex and Hyalella azteca). Bioconcentration experiments were carried out at four different temperatures with a mixture of 12 exposure relevant polar organic contaminants. Tissue and medium samples were taken in regular intervals and analysed by online solid-phase extraction liquid chromatography high-resolution tandem mass spectrometry. Subsequently, toxicokinetic rates were modelled and analysed in dependence of the exposure temperature using the Arrhenius equation. An exponential relationship between toxicokinetic rates versus temperature was observed and could be well depicted by applying the Arrhenius equation. Due to a similar Arrhenius temperature of uptake and elimination rates, the bioconcentration factors of the contaminants were generally constant across the temperature range. Furthermore, the Arrhenius temperature of the toxicokinetic rates and respiration was mostly similar. However, in some cases (citalopram, cyprodinil), the bioconcentration factor appeared to be temperature dependent, which could potentially be explained by the influence of temperature on active uptake mechanisms or biotransformation. The observed temperature effects on toxicokinetics may be particularly relevant in non-equilibrated systems, such as exposure peaks in summer as exemplified by the exposure modelling of a field measured pesticide peak where the internal concentrations increased by up to fourfold along the temperature gradient. The results provide novel insights into the mechanisms of chemical uptake, biotransformation and elimination in different climate scenarios and can improve environmental risk assessment.     

Central chemoreflex sensitivity and sympathetic neural outflow in elite breath-hold divers.

Repeated hypoxemia in obstructive sleep apnea patients increases sympathetic activity, thereby promoting arterial hypertension. Elite breath-holding divers are exposed to similar apneic episodes and hypoxemia. We hypothesized that trained divers would have increased resting sympathetic activity and blood pressure, as well as an excessive sympathetic nervous system response to hypercapnia. We recruited 11 experienced divers and 9 control subjects. During the diving season preceding the study, divers participated in 7.3 +/- 1.2 diving fish-catching competitions and 76.4 +/- 14.6 apnea training sessions with the last apnea 3-5 days before testing. We monitored beat-by-beat blood pressure, heart rate, femoral artery blood flow, respiration, end-tidal CO(2), and muscle sympathetic nerve activity (MSNA). After a baseline period, subjects began to rebreathe a hyperoxic gas mixture to raise end-tidal CO(2) to 60 Torr. Baseline MSNA frequency was 31 +/- 11 bursts/min in divers and 33 +/- 13 bursts/min in control subjects. Total MSNA activity was 1.8 +/- 1.5 AU/min in divers and 1.8 +/- 1.3 AU/min in control subjects. Arterial oxygen saturation did not change during rebreathing, whereas end-tidal CO(2) increased continuously. The slope of the hypercapnic ventilatory and MSNA response was similar in both groups. We conclude that repeated bouts of hypoxemia in elite, healthy breath-holding divers do not lead to sustained sympathetic activation or arterial hypertension. Repeated episodes of hypoxemia may not be sufficient to drive an increase in resting sympathetic activity in the absence of additional comorbidities.