Comparison of CMIP5 and CMIP6 GCM performance for flood projections in the Mekong River Basin

Study region: Mekong River Basin. Study focus: The Coupled Model Intercomparison Project Phase 6 (CMIP6) recently announced an updated version of general circulation models (GCMs). This study investigated the performance of improved CMIP6 over those of CMIP5 with respect to precipitation and flood representations in the Mekong River Basin (MRB). The correlation and error comparison from the referenced precipitation exhibited a significant improvement in the peak value representation. Hence, the impacts of climate change on future floods in the MRB were simulated and assessed using a distributed rainfall–runoff–inundation model. New hydrological insights for the region: The results indicated that precipitation from CMIP6 had a higher correlation and a lower error coefficient than CMIP5. Similarly, the simulation of GCM ensembles of monthly discharge from CMIP6 exhibited a comparable average value to the observations, whereas CMIP5 underestimated the discharge simulations. The performance of the mean annual peak discharge improved from 37, 220 m3/s (CMIP5) to 45, 423 m3/s (CMIP6) compared to 43, 521 m3/s (observation). The projections of future floods in the MRB from CMIP6 exhibited an increase of annual peak discharge at Chiang Saen, Vientiane, Pakse, and Kratie stations by 10–15%, 20–22%, and 24–29% for the SSP2-4.5 scenario, and 10–18%, 24–29%, and 41–54% for the SSP5-8.5 scenario in the near future (2026–2050), mid-future (2051–2075), and far future (2076–2100), respectively. The statistical K-S test showed significant changes in all stations and projected periods with a p-value < 0.01

Comparison of Gridded Precipitation Datasets for Rainfall-Runoff and Inundation Modeling in the Mekong River Basin

Precipitation, as a primary hydrological variable in the water cycle plays an important role in hydrological modeling. The reliability of hydrological modeling is highly related to the quality of precipitation data. Accurate long-term gauged precipitation in the Mekong River Basin, however, is limited. Therefore, the main objective of this study is to assess the performances of various gridded precipitation datasets in rainfall-runoff and flood-inundation modeling of the whole basin. Firstly, the performance of the Rainfall-Runoff-Inundation (RRI) model in this basin was evaluated using the gauged rainfall. The calibration (2000–2003) and validation (2004–2007) results indicated that the RRI model had acceptable performance in the Mekong River Basin. In addition, five gridded precipitation datasets including APHRODITE, GPCC, PERSIANN-CDR, GSMaP (RNL), and TRMM (3B42V7) from 2000 to 2007 were applied as the input to the calibrated model. The results of the simulated river discharge indicated that TRMM, GPCC, and APHRODITE performed better than other datasets. The statistical index of the annual maximum inundated area indicated similar conclusions. Thus, APHRODITE, TRMM, and GPCC precipitation datasets were considered suitable for rainfall-runoff and flood inundation modeling in the Mekong River Basin. This study provides useful guidance for the application of gridded precipitation in hydrological modeling in the Mekong River basin

Oxygen Isotope Exchange Between Molten Silicate Spherules and Ambient Water Vapor with Nonzero Relative Velocity: Implication for Chondrule Formation Environment

Oxygen isotope compositions of chondrules reflect the environment of chondrule formation and its spatial and temporal variations. Here, we present a theoretical model of oxygen isotope exchange reaction between molten silicate spherules and ambient water vapor with finite relative velocity. We found a new phenomenon, that is, mass-dependent fractionation caused by isotope exchange with ambient vapor moving with nonzero relative velocity. We also discussed the plausible condition for chondrule formation from the point of view of oxygen isotope compositions. Our findings indicate that the relative velocity between chondrules and ambient vapor would be lower than several 100 m/s when chondrules crystallized.Comment: 15 pages, 8 figures. Accepted for publication in Icaru

Gut microbial metabolites of linoleic acid are metabolized by accelerated peroxisomal β-oxidation in mammalian cells

Microorganisms in animal gut produce unusual fatty acids from the ingested diet. Two types of hydroxy fatty acids (HFAs), 10-hydroxy-cis-12-octadecenoic acid (HYA) and 10-hydroxy-octadecanoic acid (HYB), are linoleic acid (LA) metabolites produced by Lactobacillus plantarum. In this study, we investigated the metabolism of these HFAs in mammalian cells. When Chinese hamster ovary (CHO) cells were cultured with HYA, approximately 50% of the supplemented HYA disappeared from the dish within 24 hours. On the other hand, the amount of HYA that disappeared from the dish of peroxisome (PEX)-deficient CHO cells was lower than 20%. Significant amounts of C2- and C4-chain-shortened metabolites of HYA were detected in culture medium of HYA-supplemented CHO cells, but not in medium of PEX-deficient cells. These results suggested that peroxisomal β-oxidation is involved in the disappearance of HYA. The PEX-dependent disappearance was observed in the experiment with HYB, but not with LA. We also found that HYA treatment up-regulates peroxisomal β-oxidation activity of human gastric MKN74 cells and intestinal Caco-2 cells. These results indicate a possibility that HFAs produced from gut bacteria affect lipid metabolism of host via modulation of peroxisomal β-oxidation activity

Role of vinculin in paracellular barrier for ions

The paracellular barrier function of tight junctions (TJs) in epithelial cell sheets is robustly maintained against mechanical fluctuations, by molecular mechanisms that are poorly understood. Vinculin is an adaptor of a mechanosensory complex at the adherens junction. Here, we generated vinculin KO Eph4 epithelial cells and analyzed their confluent cell-sheet properties. We found that vinculin is dispensable for the basic TJ structural integrity and the paracellular barrier function for larger solutes. However, vinculin is indispensable for the paracellular barrier function for ions. In addition, TJs stochastically showed dynamically distorted patterns in vinculin KO cell sheets. These KO phenotypes were rescued by transfecting full-length vinculin and by relaxing the actomyosin tension with blebbistatin, a myosin II ATPase activity inhibitor. Our findings indicate that vinculin resists mechanical fluctuations to maintain the TJ paracellular barrier function for ions in epithelial cell sheets

ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish.

ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra

1-hydroxyyohimbine and its derivatives: new potent α2-blockers for the treatment of erectile dysfunction

金沢大学大学院自然科学研究科生理活性物質科学金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学

精神疾患におけるマイクログリア由来ニューレグリン発現

Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.博士（医学）・乙第1404号・平成29年6月28日Copyright © 2017 Elsevier Inc. All rights reserved

microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity

褐色脂肪細胞の燃焼を促す新たなメカニズムを解明 --体の熱産生にマイクロRNA-33が関与--. 京都大学プレスリリース. 2021-02-17.Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33−/− mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33f/f dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)A receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33f/f DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress