Identical NR5A1 Missense Mutations in Two Unrelated 46,XX Individuals with Testicular Tissues

The role of monogenic mutations in the development of 46,XX testicular/ovotesticular disorders of sex development (DSD) remains speculative. Although mutations in NR5A1 are known to cause 46,XY gonadal dysgenesis and 46,XX ovarian insufficiency, such mutations have not been implicated in testicular development of 46,XX gonads. Here, we identified identical NR5A1 mutations in two unrelated Japanese patients with 46,XX testicular/ovotesticular DSD. The p.Arg92Trp mutation was absent from the clinically normal mothers and from 200 unaffected Japanese individuals. In silico analyses scored p.Arg92Trp as probably pathogenic. In vitro assays demonstrated that compared with wild‐type NR5A1, the mutant protein was less sensitive to NR0B1‐induced suppression on the SOX9 enhancer element. Other sequence variants found in the patients were unlikely to be associated with the phenotype. The results raise the possibility that specific mutations in NR5A1 underlie testicular development in genetic females

27ヒドロキシコレステロールはエストロゲン受容体を介してヒトSLC22A12の発現を制御する

The excretion and reabsorption of uric acid both to and from urine are tightly regulated by uric acid transporters. Metabolic syndrome conditions, such as obesity, hypercholesterolemia, and insulin resistance, are believed to regulate the expression of uric acid transporters and decrease the excretion of uric acid. However, the mechanisms driving cholesterol impacts on uric acid transporters have been unknown. Here, we show that cholesterol metabolite 27-hydroxycholesterol (27HC) upregulates the uric acid reabsorption transporter URAT1 encoded by SLC22A12 via estrogen receptors (ER). Transcriptional motif analysis showed that the SLC22A12 gene promoter has more estrogen response elements (EREs) than other uric acid reabsorption transporters such as SLC22A11 and SLC22A13, and 27HC-activated SLC22A12 gene promoter via ER through EREs. Furthermore, 27HC increased SLC22A12 gene expression in human kidney organoids. Our results suggest that in hypercholesterolemic conditions, elevated levels of 27HC derived from cholesterol induce URAT1/SLC22A12 expression to increase uric acid reabsorption, and thereby, could increase serum uric acid levels.博士（医学）・甲第772号・令和3年3月15日© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes

Prolactin and Upstream Migration of the Amphidromous Teleost, Ayu Plecoglossus altivelis

Changes in mRNA levels of prolactin (PRL) during the upstream migration were examined in fry of the amphidromous fish, ayu Plecoglossus altivelis. Quantification of mRNA has been done with real-time PCR and expressed as whole body or pituitary contents depending the body size of fry. PRL mRNA levels of ayu caught in seawater of the coastal area remained low during early spring. Prior to the start of the upstream migration, the fish caught in the coastal area in mid spring showed increased levels of PRL mRNA. There were further increases in PRL levels in the fish caught in the river. Analysis of proportions revealed that there were significant differences among PRL mRNA in the fish caught in different environmental salinities. Body weight showed a positive relation with PRL mRNA in ayu caught in seawater. A landlocked population of ayu, which migrates from lake to river, showed no significant change in PRL mRNA levels before and after upstream migration. Results in this study indicate the importance of up-regulation of PRL gene expression of ayu during the upstream migration from seawater to fresh water. There is a possible relationship between body size and PRL in the early developmental stage of ayu in seawater, but not in the fish in fresh water

A Model of Ischemia-Induced Neuroblast Activation in the Adult Subventricular Zone

We have developed a rat brain organotypic culture model, in which tissue slices contain cortex-subventricular zone-striatum regions, to model neuroblast activity in response to in vitro ischemia. Neuroblast activation has been described in terms of two main parameters, proliferation and migration from the subventricular zone into the injured cortex. We observed distinct phases of neuroblast activation as is known to occur after in vivo ischemia. Thus, immediately after oxygen/glucose deprivation (6–24 hours), neuroblasts reduce their proliferative and migratory activity, whereas, at longer time points after the insult (2 to 5 days), they start to proliferate and migrate into the damaged cortex. Antagonism of ionotropic receptors for extracellular ATP during and after the insult unmasks an early activation of neuroblasts in the subventricular zone, which responded with a rapid and intense migration of neuroblasts into the damaged cortex (within 24 hours). The process is further enhanced by elevating the production of the chemoattractant SDf-1α and may also be boosted by blocking the activation of microglia. This organotypic model which we have developed is an excellent in vitro system to study neurogenesis after ischemia and other neurodegenerative diseases. Its application has revealed a SOS response to oxygen/glucose deprivation, which is inhibited by unfavorable conditions due to the ischemic environment. Finally, experimental quantifications have allowed us to elaborate a mathematical model to describe neuroblast activation and to develop a computer simulation which should have promising applications for the screening of drug candidates for novel therapies of ischemia-related pathologies

Loss of DPP4 activity is related to a prothrombogenic status of endothelial cells: implications for the coronary microvasculature of myocardial infarction patients

Pro-coagulant and pro-inflammatory intramyocardial (micro)vasculature plays an important role in acute myocardial infarction (AMI). Currently, inhibition of serine protease dipeptidyl peptidase 4 (DPP4) receives a lot of interest as an anti-hyperglycemic therapy in type 2 diabetes patients. However, DPP4 also possesses anti-thrombotic properties and may behave as an immobilized anti-coagulant on endothelial cells. Here, we studied the expression and activity of endothelial DPP4 in human myocardial infarction in relation to a prothrombogenic endothelial phenotype. Using (immuno)histochemistry, DPP4 expression and activity were found on the endothelium of intramyocardial blood vessels in autopsied control hearts (n = 9). Within the infarction area of AMI patients (n = 73), this DPP4 expression and activity were significantly decreased, coinciding with an increase in Tissue Factor expression. In primary human umbilical vein endothelial cells (HUVECs), Western blot analysis and digital imaging fluorescence microscopy revealed that DPP4 expression was strongly decreased after metabolic inhibition, also coinciding with Tissue Factor upregulation. Interestingly, inhibition of DPP4 activity with diprotin A also enhanced the amount of Tissue Factor encountered and induced the adherence of platelets under flow conditions. Ischemia induces loss of coronary microvascular endothelial DPP4 expression and increased Tissue Factor expression in AMI as well as in vitro in HUVECs. Our data suggest that the loss of DPP4 activity affects the anti-thrombogenic nature of the endothelium

Pathogenic Roles of CD14, Galectin-3, and OX40 during Experimental Cerebral Malaria in Mice

An in-depth knowledge of the host molecules and biological pathways that contribute towards the pathogenesis of cerebral malaria would help guide the development of novel prognostics and therapeutics. Genome-wide transcriptional profiling of the brain tissue during experimental cerebral malaria (ECM ) caused by Plasmodium berghei ANKA parasites in mice, a well established surrogate of human cerebral malaria, has been useful in predicting the functional classes of genes involved and pathways altered during the course of disease. To further understand the contribution of individual genes to the pathogenesis of ECM, we examined the biological relevance of three molecules – CD14, galectin-3, and OX40 that were previously shown to be overexpressed during ECM. We find that CD14 plays a predominant role in the induction of ECM and regulation of parasite density; deletion of the CD14 gene not only prevented the onset of disease in a majority of susceptible mice (only 21% of CD14-deficient compared to 80% of wildtype mice developed ECM, p<0.0004) but also had an ameliorating effect on parasitemia (a 2 fold reduction during the cerebral phase). Furthermore, deletion of the galectin-3 gene in susceptible C57BL/6 mice resulted in partial protection from ECM (47% of galectin-3-deficient versus 93% of wildtype mice developed ECM, p<0.0073). Subsequent adherence assays suggest that galectin-3 induced pathogenesis of ECM is not mediated by the recognition and binding of galectin-3 to P. berghei ANKA parasites. A previous study of ECM has demonstrated that brain infiltrating T cells are strongly activated and are CD44+CD62L− differentiated memory T cells [1]. We find that OX40, a marker of both T cell activation and memory, is selectively upregulated in the brain during ECM and its distribution among CD4+ and CD8+ T cells accumulated in the brain vasculature is approximately equal

Western Pacific Air-Sea Interaction Study

A01: Dynamics of Atmospheric CompositionA Study on the Production and Emission of Marine-Derived Volatile Halocarbons / Y. Yokouchi, A. Ooki, S. Hashimoto and N. Itoh : 05w-pass_001.pdfMeasurements of Gaseous Peroxides in the Oceanic Lower Atmosphere / S. Hatakeyama and T. Akatsuka : 06w-pass_027.pdfPhase Partitioning of NH3 and Gas to Particle Conversion / K. Osada : 07w-pass_033.pdfNew Particle Formation of Marine Aerosols / K. Miura, H. Furutani, Y. Iwamoto, K. Nagano, H. Kobayashi, M. Mochida, H. Mukai, S. Hashimoto, M. Takami and M. Uematsu : 08w-pass_037.pdfA Study of the Chemical Processes in Aerosols and Their Impacts on the Environment Using X-ray Absorption Fine Structure Spectroscopy / Y. Takahashi, M. Higashi, T. Furukawa, T. Miyoshi, M. Fujiwara and M. Uematsu : 09w-pass_043.pdfVariability in Mineral Dust Deposition over the North Pacific and Its Potential Impact on the Ocean Productivity / H. Fukushima : 10w-pass_051.pdfAtmosphere-Ocean Interaction through Atmospheric Aerosol Particles Observed in a Single Nanoparticle Aspect / H. Furutani, J. Jinyoung and M. Uematsu : 11w-pass_061.pdfSimultaneous Measurements of Hygroscopic Property and Cloud Condensation Nucleus Activity of Aerosol Particles of Marine Biogenic Origin / M. Mochida : 12w-pass_071.pdfEruption of Mt. Kilauea Impacted Cloud Droplet and Radiation Budget over North Pacific / I. Uno, K. Eguchi and K. Yumimoto : 13w-pass_083.pdfA02: Variability of Gas Exchanges at the Air-Sea InterfaceHigh-Resolution Measurement of Volatile Organic Compounds Dissolved in Seawater Using Equilibrator Inlet-Proton Transfer Reaction-Mass Spectrometry (EI-PTR-MS) / H. Tanimoto, S. Kameyama, Y. Omori, S. Inomata and U. Tsunogai : 14w-pass_089.pdfStudy of the Production Processes of Marine Biogenic Methane and Carbonyl Sulfide Using Stable Isotope Analysis / S. Toyoda, K. Yamada, Y. Ueno, K. Koba and O. Yoshida : 15w-pass_117.pdfLong-Term Changes of Greenhouse Gases in the Ocean and Their Feedback Effects on the Climate / Y. W. Watanabe, I. Yasuda and N. Tsurushima : 16w-pass_123.pdfTemporal and Spatial Variations in Carbonate System and Air-Sea CO2 Flux in the Kuroshio and Kuroshio Extension / H. Yoshikawa-Inoue, T. Midorikawa and T. R. Takamura : 17w-pass_151.pdfA03: Dynamics of the Marine EcosystemBioavailability and Biogeochemical Processes of Trace Metals in the Surface Ocean / S. Takeda, H. Obata, A. Okubo, M. Sato and Y. Kondo : 18w-pass_163.pdfDetailed Variations in Bioactive Elements in the Surface Ocean and Their Interaction with Microbiological Processes / H. Ogawa, K. Kogure, J. Kanda, F. Hashihama and M. Suzumura : 19w-pass_177.pdfPhotoheterotrophic Process in Surface Seawater Environments / K. Hamasaki, Y. Sato-Takabe, A. Taniguchi and Y. Tada : 20w-pass_199.pdfEcological Study of Bacterial Populations Related to Biogenic Gas Transformation in Marine Environments / K. Hamasaki, R. Kaneko, A. Mouri, Y. Tada, N. Kasamatsu-Takasawa and I. Nagao : 21w-pass_203.pdfA04: Modelling of the Interaction between the Ocean and the AtmosphereModeling for Evaluation and Prediction of Effects of Short-Term Atmospheric Disturbance on Air-Sea Material Cycling / M. Fujii and A. Tanaka : 22w-pass_211.pdfRelating Phytoplankton Pnysiology to North Pacific Biogeochemistry / S. L. Smith, M. N. Aita, M. Shigemitsu and Y. Yamanaka : 23w-pass_223.pdfCoupling of Physical and Bio-Geochemical Process and Monitoring Ocean Circulation Using Data Assimilation System / Y. Ishikawa, T. Awaji, M. Ikeda and T. Toyoda : 24w-pass_237.pdfPart of "Western Pacific Air-Sea Interaction Study

Western Pacific Air-Sea Interaction Study

A01: Dynamics of Atmospheric CompositionA Study on the Production and Emission of Marine-Derived Volatile Halocarbons / Y. Yokouchi, A. Ooki, S. Hashimoto and N. Itoh : 05w-pass_001.pdfMeasurements of Gaseous Peroxides in the Oceanic Lower Atmosphere / S. Hatakeyama and T. Akatsuka : 06w-pass_027.pdfPhase Partitioning of NH3 and Gas to Particle Conversion / K. Osada : 07w-pass_033.pdfNew Particle Formation of Marine Aerosols / K. Miura, H. Furutani, Y. Iwamoto, K. Nagano, H. Kobayashi, M. Mochida, H. Mukai, S. Hashimoto, M. Takami and M. Uematsu : 08w-pass_037.pdfA Study of the Chemical Processes in Aerosols and Their Impacts on the Environment Using X-ray Absorption Fine Structure Spectroscopy / Y. Takahashi, M. Higashi, T. Furukawa, T. Miyoshi, M. Fujiwara and M. Uematsu : 09w-pass_043.pdfVariability in Mineral Dust Deposition over the North Pacific and Its Potential Impact on the Ocean Productivity / H. Fukushima : 10w-pass_051.pdfAtmosphere-Ocean Interaction through Atmospheric Aerosol Particles Observed in a Single Nanoparticle Aspect / H. Furutani, J. Jinyoung and M. Uematsu : 11w-pass_061.pdfSimultaneous Measurements of Hygroscopic Property and Cloud Condensation Nucleus Activity of Aerosol Particles of Marine Biogenic Origin / M. Mochida : 12w-pass_071.pdfEruption of Mt. Kilauea Impacted Cloud Droplet and Radiation Budget over North Pacific / I. Uno, K. Eguchi and K. Yumimoto : 13w-pass_083.pdfA02: Variability of Gas Exchanges at the Air-Sea InterfaceHigh-Resolution Measurement of Volatile Organic Compounds Dissolved in Seawater Using Equilibrator Inlet-Proton Transfer Reaction-Mass Spectrometry (EI-PTR-MS) / H. Tanimoto, S. Kameyama, Y. Omori, S. Inomata and U. Tsunogai : 14w-pass_089.pdfStudy of the Production Processes of Marine Biogenic Methane and Carbonyl Sulfide Using Stable Isotope Analysis / S. Toyoda, K. Yamada, Y. Ueno, K. Koba and O. Yoshida : 15w-pass_117.pdfLong-Term Changes of Greenhouse Gases in the Ocean and Their Feedback Effects on the Climate / Y. W. Watanabe, I. Yasuda and N. Tsurushima : 16w-pass_123.pdfTemporal and Spatial Variations in Carbonate System and Air-Sea CO2 Flux in the Kuroshio and Kuroshio Extension / H. Yoshikawa-Inoue, T. Midorikawa and T. R. Takamura : 17w-pass_151.pdfA03: Dynamics of the Marine EcosystemBioavailability and Biogeochemical Processes of Trace Metals in the Surface Ocean / S. Takeda, H. Obata, A. Okubo, M. Sato and Y. Kondo : 18w-pass_163.pdfDetailed Variations in Bioactive Elements in the Surface Ocean and Their Interaction with Microbiological Processes / H. Ogawa, K. Kogure, J. Kanda, F. Hashihama and M. Suzumura : 19w-pass_177.pdfPhotoheterotrophic Process in Surface Seawater Environments / K. Hamasaki, Y. Sato-Takabe, A. Taniguchi and Y. Tada : 20w-pass_199.pdfEcological Study of Bacterial Populations Related to Biogenic Gas Transformation in Marine Environments / K. Hamasaki, R. Kaneko, A. Mouri, Y. Tada, N. Kasamatsu-Takasawa and I. Nagao : 21w-pass_203.pdfA04: Modelling of the Interaction between the Ocean and the AtmosphereModeling for Evaluation and Prediction of Effects of Short-Term Atmospheric Disturbance on Air-Sea Material Cycling / M. Fujii and A. Tanaka : 22w-pass_211.pdfRelating Phytoplankton Pnysiology to North Pacific Biogeochemistry / S. L. Smith, M. N. Aita, M. Shigemitsu and Y. Yamanaka : 23w-pass_223.pdfCoupling of Physical and Bio-Geochemical Process and Monitoring Ocean Circulation Using Data Assimilation System / Y. Ishikawa, T. Awaji, M. Ikeda and T. Toyoda : 24w-pass_237.pdfPart of "Western Pacific Air-Sea Interaction Study