Variations of olfactory function with circadian timing and chronotype.

BACKGROUND: Cumulative animal studies have suggested that olfaction can be regulated by circadian clock. However, human studies on the topic are relatively limited. The present study thus aimed to investigate diurnal variation in olfaction in healthy adults while examining potential modulating factors. METHODS: We conducted four rounds of testing on 56 healthy adults (32 women) aged 31 ± 12 years, throughout a single day, during morning (8:00-10:00 h), noon (12:00-14:00 h), afternoon (16:00-18:00 h), and evening (20:00-22:00 h). At the first appointment, participants completed full olfactory function testing using the Sniffin’ Sticks, questionnaires on medical history, nasal symptoms, sleep quality, and chronotype, and were assessed for blood pressure, heart rate, peak nasal inspiratory flow (PNIF), attention level, and rated their smell ability, nasal patency, wakefulness, and concentration level using visual analog scale (VAS) ratings. Subsequent appointments measured olfactory threshold, attentional level, PNIF, blood pressure, heart rate and VAS ratings repeatedly. RESULTS: Olfactory threshold (OT) scores varied significantly between different times of the day, with the highest score in the evening and the lowest in the morning. Similar differences were also observed in PNIF, with the highest value in the evening and the lowest in the morning. However, there were no significant correlations between OT score and PNIF across all four-time testing, as well as between differences in [OT evening â€" OT morning] and [PNIF evening â€" PNIF morning]. Furthermore, a generalized linear mixed model indicated that the testing time of the morning, evening chronotype, self-reported body mass index (BMI), rated smell ability, and rated nasal patency significantly predicted the Sniffin' Sticks OT score. CONCLUSIONS: Olfactory function fluctuates throughout the waking hours of the day, with the highest olfactory sensitivity observed in the evening and the lowest in the morning. This pattern is also seen in nasal patency. However, it appears that the circadian changes of nasal airflow may not significantly depend on the circadian changes of the olfactory sensitivity. In addition, chronotype and BMI may regulate such olfactory-circadian variation. These findings provide important insights for future research on the accurate diagnosis and treatment of olfactory dysfunction.

The RNA export factor Gle1p is located on the cytoplasmic fibrils of the NPC and physically interacts with the FG-nucleoporin Rip1p, the DEAD-box protein Rat8p/Dbp5p and a new protein Ymr 255p.

Gle1p is an essential, nuclear pore complex (NPC)-associated RNA export factor. In a screen for high copy suppressors of a GLE1 mutant strain, we identified the FG-nucleoporin Rip1p and the DEAD-box protein Rat8p/Dbp5p, both of which have roles in RNA export; we also found Ymr255p/Gfd1p, a novel inessential protein. All three high copy suppressors interact with the C-terminal domain of Gle1p; immunoelectron microscopy localizations indicate that Gle1p, Rip1p and Rat8p/Dbp5p are present on the NPC cytoplasmic fibrils; Rip1p was also found within the nucleoplasm and on the nuclear baskets. In vivo localizations support the hypothesis that Rip1p contributes to the association of Gle1p with the pore and that Gle1p, in turn, provides a binding site for Rat8p/Dbp5p at the NPC. These data are consistent with the view that Gle1p, Rip1p, Rat8p/Dbp5p and Ymr255p/Gfd1p associate on the cytoplasmic side of the NPC to act in a terminal step of RNA export. We also describe a human functional homologue of Rip1p, called hCG1, which rescues Rip1p function in yeast, consistent with the evolutionary conservation of this NPC-associated protein.