Biology subjects

Nagai, N.

Publications and source records attributed to Nagai, N..

6 recordsLinked to original sources

bioRxiv2026

Evolutionary history of aquaporin-10 pseudogenization in Cetartiodactyla

Aquaporin-10 (AQP10) is an aquaglyceroporin that transports small, uncharged molecules, such as water and glycerol. In some species, such as mice and cattle, the AQP10 gene (Aqp10) is pseudogenized. In rodents, pseudogenization of Aqp10 is limited to the Myomorpha suborder, while Aqp10 remains intact in other rodent lineages. The order Cetartiodactyla encompasses diverse species, including Suina, Tylopoda, Ruminantia, and Whippomorpha. The distribution of intact Aqp10 across the entire Cetartiodactyla and analyses estimating the timing of Aqp10 pseudogenization have not been sufficiently investigated. In this study, we identified species within Cetartiodactyla that retain intact Aqp10 and analyzed the detailed patterns of pseudogenization to elucidate the specifics of pseudogenization within this order. We collected Aqp10 loci by BLAST and synteny analyses of publicly available genome databases of 51 cetartiodactyl species from 17 families. Dot plot and alignment analyses revealed that seudogenization of Aqp10 occurred in 42 Cetartiodactyla species, including the Camelidae, warthog (Suidae), Antilocapridae, okapi (Giraffidae), Cervidae, Bovidae, Hippopotamidae, and Cetacea. In contrast, nine species retained an intact Aqp10: pig and babirusa (Suidae), peccary (Tayassuidae), mouse deeres (Tragulidae), giraffes (Giraffidae), and musk deers (Moschidae). The timing of pseudogenization was estimated by comparing patterns of exon deletions, frameshifts, and nonsense mutations in Aqp10 pseudogenes. RT-PCR analysis of cattle and sheep tissues revealed that these species express Aqp3 and Aqp7 in their intestines, but not Aqp10. Collectively, these findings indicate that Aqp10 pseudogenization occurred independently in multiple cetartiodactyl lineages and provide new insights into the evolutionary history of Aqp10 loss within this order.

evolutionary biology↗

bioRxiv2024

Allometric multi-scaling of weight-for-height relation in children and adolescents: Revisiting the theoretical basis of body mass index of thinness and obesity assessment

The body mass index (BMI), defined as weight in kilograms divided by height in meters squared, has been widely used to assess thinness and obesity in all age groups, including children and adolescents. However, the validity and utility of BMI as a reliable measure of nutritional health have been questioned. This study discusses the mathematical conditions that support the validity of BMI based on population statistics. Here, we propose a condition defined as allometric uni-scaling to ensure the validity of BMI as an objective height-adjusted measure. Any given centile curve, including the median curve, in a weight-for-height distribution should be approximated using power-law functions with the same scaling exponent. In contrast, when the scaling exponent varies depending on the position of the centile curve, it is called allometric multi-scaling. By introducing a method for testing these scaling properties using quantile regression, we analyzed a large-scale Japanese database that included 7,863,520 children aged 5-17 years. We demonstrated the remarkable multi-scaling properties at ages 5-13 years for males and 5-11 years for females, and the convergence to uni-scaling with a scaling exponent close to 2 as they approached 17 years of age for both sexes. We confirmed that conventional BMI is appropriate as an objective height-adjusted mass measure at least 17 years of age, close to adulthood, for both males and females. However, the validity of BMI could not be confirmed in younger age groups. Our findings indicate that the growth of childrens weight-for-height relation is much more complex than previously assumed. Therefore, a single BMI-type formula cannot be used to assess thinness and obesity in children and adolescents.

biophysics↗

bioRxiv2022

Inflammatory response induced in pulmonary embolic lung: Evaluation usinga reproducible murine pulmonary embolism model.

BackgroundSince previously established models of pulmonary embolism showed a large variability in the degree of ischemia, it is difficult to assess the pathophysiological response in the lung after embolization. Here, we established a model of pulmonary embolism by certain amount of relatively small thrombi, in which the degree of ischemia was reproducible. MethodsThrombi with a maximum diameter of 100 m or 500 m were administered intravenously under anesthesia, and the survival ratio at 4 hours was evaluated. The location of thrombi in the lung was visualized by administration of fluorescent-labeled thrombus, and the hemodynamics of the lung after administration of thrombi was evaluated. CT angiography was also performed to evaluate the ratio of the embolized vessels. In addition, cytokine mRNAs was quantified 4 hours in embolized lung. Immunohistochemical analysis for interleukin (IL)-6 and CD68 as a marker of macrophages were also performed. ResultsIt was found that mice with 100 m clots, but not with 500 m clots, showed a dose-dependence of survival between 2.3 L/g and 3.0 L/g at 4 hours from embolization induction. In mice treated with 2.5 L/g of 100 m thrombus, thrombi were located in the peripheral region of the lung, which was consistent with the disruption of blood circulation the peripheral region. In addition, about 60% of the vessels with a diameter of less than 100 m were occluded in these mice. In the lungs after 4 hours of embolization, IL-6 mRNA and tumor necrosis factor (TNF)- mRNA were significantly higher and lower than control lungs. IL-6 was expressed in CD68-positive macrophages in both embolized and control lungs after 4 hours of embolization, and the number of each positive cells were comparable in both embolized and control lungs. ConclusionsThese results show that the pulmonary embolization model induced by a certain amount of small thrombus is useful for evaluating the pathological responses in the embolized lung. Furthermore, it was found that IL-6 expression was increased in macrophages in the embolized lung, indicating that inflammatory responses may contribute to the pathogenesis of pulmonary embolism.

pathology↗

bioRxiv2022

Toxicity of House Cricket (Acheta domesticus) in Mice

There is an urgent need to address the shortage of animal protein due to food shortages caused by the global population growth. Crickets contain an abundance of proteins in their exoskeleton and muscles and have attracted attention as a new protein source; however, their safety as a food source has not been confirmed. We evaluated the toxicity of the House cricket (Acheta domesticus), on cells and mammals. In genotoxicity in vitro, cricket powder was added to Chinese hamster lung CHL-IU cells at concentrations of 5,000 {micro}g/mL, and the rate of chromosomal aberrations was assessed. In genotoxicity in vivo, mice were orally administered up to 2,000 mg/kg of cricket powder for 2 days. In both tests, cricket powder did not show any toxic effect. A repeated oral toxicity study was performed administering up to 3,000 mg/kg of cricket powder or control (saline) for 14 or 90 consecutive days and measuring body weight changes, blood biochemistry, blood properties, and organ weights. In each time course, there were no differences in there parameters between the control and cricket powder treated groups. These results suggest that House crickets ([≤]3,000 mg/kg) are not toxic to cells and organisms.

pharmacology and toxicology↗

bioRxiv2021

Plasmin-mediated cleavage of EphA4 at central amygdala inhibitory synapses controls anxiety

Severe stress can trigger complex behavioural changes such as high anxiety (1). Inhibitory GABA-ergic interneurons in the lateral division of the central amygdala (CEl) control anxiety through feedforward inhibition of their target cells in the medial division (CEm) (2, 3). In particular, PKC{delta}-positive (PKC{delta}+) interneurons in CEl are critical elements of the neuronal circuitry of fear and anxiety (3-5), but the molecular mechanisms they employ are poorly understood. Here, we show that, during stress, GABA-ergic synapses of amygdala PKC{delta}+ interneurons are regulated by a serine protease plasmin. On stress, plasmin cleaves the extracellular portion of the tyrosine kinase receptor EphA4 triggering its dissociation from gephyrin, a postsynaptic GABA-receptor anchoring protein. Dynamic EphA4/gephyrin interaction leads to modification of dendritic spine morphology and synaptic GABA-receptor expression profile. Consistent with the critical role for the plasmin/EphA4/gephyrin signalling axis in anxiogenesis, viral delivery of plasmin-resistant (prEphA4) form of EphA4 into the central amygdala prevents the development of stress-induced anxiety in mice, while the delivery of plasmin-truncated EphA4 (tEphA4) dramatically enhances this effect. Thus, our studies identify a novel, critical molecular cascade regulating GABA-ergic signalling in the central amygdala synapses that allows bidirectional switching of animal behaviour from high to low anxiety states.

neuroscience↗

bioRxiv2019

Lysine demethylase 7a regulates the anterior-posterior development in mouse by modulating the transcription of Hox gene cluster

Temporal and spatial colinear expression of the Hox genes determines the specification of positional identities during vertebrate development. Post-translational modifications of histones contribute to transcriptional regulation. Lysine demethylase 7A (Kdm7a) demethylates lysine 9 di-methylation of histone H3 (H3K9me2) and participates in the transcriptional activation of developmental genes. However, the role of Kdm7a during mouse embryonic development remains to be elucidated. Here, we show that Kdm7a-/- mouse exhibits an anterior homeotic transformation of the axial skeleton, including an increased number of presacral elements. Importantly, posterior Hox genes (caudally from Hox9) are specifically downregulated in the Kdm7a-/- embryo, which correlates with increased levels of H3K9me2. These observations suggest that Kdm7a controls the transcription of posterior Hox genes, likely via its demethylating activity, and thereby regulating the murine anterior-posterior development. Such epigenetic regulatory mechanisms may be harnessed for the proper control of coordinate body patterning in vertebrates.

molecular biology↗