Biology subjects

Yano, T.

Publications and source records attributed to Yano, T..

3 recordsLinked to original sources

bioRxiv2022

A mouse model of insomnia with sleep apnea

Obstructive sleep apnea (OSA) patients are exposed to nighttime hypoxia during sleep by intermittent airway closure and feel daytime strong sleepiness. Strangely, insomnia co-occur in some OSA patients, which is called co-morbid insomnia and sleep apnea (COMISA). Here, we show activity responses to daytime hypoxia (DHx) in nocturnal mice were comparable to daytime sleepiness and co-occurring nighttime insomnia in COMISA. DHx reduced activity in active phase (AP) and increased following activity in activity ending phase (AEP). This down-and-up activity response (DUR) by DHx was also observed in molecular clock deficient Cry1 and Cry2 double knockout mice (CryDKO) expressing nighttime activity rise under light-dark cycle (LD) and not observed in arrhythmic CryDKO under constant darkness (DD). When daytime timing hypoxia was exposed at transition from LD to DD, about every 6 h down and up and down wavelike activity responses appeared in arrhythmic CryDKO. Results indicate this wavelike response and AP activity overlap and cause DUR in rhythmic mice. DHx increased plasma corticosterone and this increase antagonized AP activity reduction by DHx. DHx reduced forebrain adenosine and morning adenosine inhibition by caffeine induced DUR. Adenosine inhibition by caffeine or istradefylline at transition from LD to DD induced wavelike response in CryDKO. It is possible that wavelike response is damped oscillation because, interestingly, chronic caffeine treatment induced circasemidian and/or circadian activity rhythms in arrhythmic CryDKO. Evening caffeine attenuated DUR by DHx, which suggested adenosine inhibition chronotherapy may improve OSA/COMISA symptoms. Our animal model will be useful to understand COMISA. SignificanceObstructive sleep apnea patients (OSA) are exposed to nighttime hypoxia during sleep. OSA feels daytime strong sleepiness and increases risk of many diseases. Insomnia occurs in not a few OSA, which is called comorbid insomnia and sleep apnea (COMISA). We show here a mouse model of COMISA. In mice, daytime hypoxia exposure induced following down and up activity response (DUR), activity reduction in active phase and increase in activity ending phase, which corresponded to sleepiness and insomnia in COMISA. We found DUR was clock gene independent and might be driven by circasemidian system. Glucocorticoid and forebrain adenosine response were involved in DUR. Caffeine chronotherapy was effective in DUR. Our model may be useful to understand COMISA.

physiology↗

bioRxiv2022

Spatio-temporal model and machine learning method reveal process of phenological shift under climate change of North Pacific spiny dogfish

Climate change has disrupted natural phenological patterns, including migration. Despite extensive studies of phenological shifts in migration by climate change and driving factors of migration, a few issues remain unresolved. In particular, little is known about the complex effects of driving factors on migration with interactions and nonlinearity, and partitioning of the effects of factors into spatial, temporal, and spatio-temporal effects. The Pacific spiny dogfish Squalus suckleyi (hereafter "spiny dogfish") is a coastal elasmobranchii that migrates southward for parturition and northward for feeding in the western North Pacific. Here, to elucidate the migration patterns as well as the driving factors under climate change, we first examined long-term changes in the timing and geographic location of migration by applying a spatio-temporal model to ca. 5-decade time series data for the presence/absence of spiny dogfish in the western North Pacific. We then evaluated the spatial, temporal, and spatio-temporal effects of driving factors (sea surface temperature [SST], depth, productivity, and magnetic fields) on seasonal occurrence patterns using a machine learning model. We found that the migration area did not change over ca. 5 decades, whereas the migration timing advanced by a month after 2000. The spatial effects of magnetic fields and depth were consistently large and the spatial and spatio-temporal effects of SST increased in the migration season, even though temporal effect of SST was always weak. These results suggest that the migration area of spiny dogfish was stable over time because their spatial distribution was determined by geographic features, whereas the migration timing advanced by tracking a suitable SST location which increased steeply after 2000. Therefore, temperature as well as other factors influence migration simultaneously under climate change and underline the importance of paying attention biotic/abiotic factors including temperature and process-based understanding to predict future impacts of climate change on phenological shifts.

ecology↗

bioRxiv2021

Identification of general acid catalyst for the ATPase activity of Lynch syndrome-related MutL homologs

Mutations of mismatch repair MutL homologs are causative of a hereditary cancer, Lynch syndrome. Investigation of MutL facilitates genetic diagnoses essential for cancer risk managements and therapies. We characterized MutL homologs from human and a hyperthermophile, Aquifex aeolicus, (aqMutL) to reveal the catalytic mechanism for the ATPase activity. Although existence of a general acid catalyst had not been conceived in the mechanism, analysis of the pH dependence of the aqMutL ATPase activity revealed that the reaction is accelerated by general acid-base catalysis. Analyses of mutant aqMutLs showed that Lys79 is the general acid, and the corresponding residues were confirmed to be critical for activities of human homologs, on the basis of which a catalytic mechanism for MutL ATPase is proposed. These and other results described here would contribute to evaluating the pathogenicity of Lynch syndrome-associated missense mutations.

biochemistry↗