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Gruber, G.

Publications and source records attributed to Gruber, G..

2 recordsLinked to original sources

Wide awake at bedtime? The effects of caffeine on sleep and circadian timing in teenagers - a randomized crossover trial

BackgroundAdolescents frequently consume caffeine with unknown consequences on sleep and circadian rhythms. In adults, the evidence indicates that caffeine acutely reduces homeostatic sleep pressure and delays the circadian timing system. ObjectiveHere, we investigated the acute effects of caffeine intake on the developing sleep-wake regulatory system of teenagers. DesignIn a double-blind randomized crossover laboratory study, 18 teenagers (16.1 {+/-} 1 years old, pubertal development scale [PDS]: 2.76 {+/-} 0.35) ingested 80 mg caffeine (vs placebo) four hours prior to bedtime. Until bedtime, participants regularly filled in the Karolinska Sleepiness Scale and gave saliva samples to measure melatonin secretion. During nighttime, we quantified homeostatic sleep need by the electroencephalographically derived amount of slow wave sleep duration (SWS). After sleep, participants rated sleep quality by the Leeds Sleep Evaluation Questionnaire. ResultsWhile participants felt less sleepy after caffeine vs. placebo (P=0.038), their ratings of sleep quality were not strongly affected by the treatment. However, objectively, SWS was on average reduced by [~]20 min after caffeine vs. placebo (P=0.026). This caffeine-induced reduction was more pronounced in those individuals with more SWS under placebo (regression: P=0.042; standardized beta=0.622, P=0.011), even if controlling for habitual caffeine intake or pubertal stage (PDS). In melatonin onsets we observed both delays and advances in response to caffeine. This variance could partly be explained by differences in relative dose (i.e., mg caffeine/kg of bodyweight): the higher the relative dose, the more likely were delays (regression: P=0.01; standardized beta=0.592, P=0.01). ConclusionsIn teenagers, evening caffeine intake of already 80 mg (i.e. [~]8fl oz of common energy drinks) is sufficient to promote alertness at the costs of subsequent sleep. These costs might be more pronounced in adolescents with a higher need for SWS. Moreover, caffeine might disturb the circadian timing system, consequently hampering the balanced interplay of sleep-wake regulatory components. Sources of SupportMarie-Heim-Voegtlin Grant of the Swiss National Science Foundation (SNSF) PMPDP1_171364

neuroscience

Phosphorylation regulates auto-inhibition of kinesin KIF3A

Kinesin are molecular motors that move along the microtubules. They function to transport cargoes, vesicles and organelles to designated locations in the cells. KIF3A belongs to the Kinesin-2 family and forms a heterotrimeric complex with KIF3B and KAP3. We have earlier shown that the cargo trafficking activity of KIF3 motor can be regulated by CaMKII kinase and POPX2 phosphatase. In this study, we elucidated the mechanism of KIF3A regulation. We find that KIF3A adopts an auto-inhibited state through the interaction between the motor and tail domains. The motor-tail interaction also hinders the ATPase activity of the motor domain. We show that the phosphorylation status of serine-689/690 (mouse/human) at the C-terminal region of KIF3A is crucial for the motor-tail interaction. The motor domain does not interact well with the tail domain when serine-689 is phosphorylated by CaMKII or mutated to aspartic acid to mimic phosphorylation. Molecular dynamics simulations suggest that the non-phosphorylated tail domain folds into the hydrophobic pocket formed by the motor dimers. Phosphorylation of serine-689 results in conformational changes that leads to the relieve of auto-inhibition.

biochemistry