Ad4BP/SF-1 regulates cholesterol synthesis to boost the production of steroids

Housekeeping metabolic pathways such as glycolysis are active in all cell types. In addition, many types of cells are equipped with cell-specific metabolic pathways. To properly perform their functions, housekeeping and cell-specific metabolic pathways must function cooperatively. However, the regulatory mechanisms that couple metabolic pathways remain largely unknown. Recently, we showed that the steroidogenic cell-specific nuclear receptor Ad4BP/ SF-1, which regulates steroidogenic genes, also regulates housekeeping glycolytic genes. Here, we identify cholesterogenic genes as the targets of Ad4BP/SF-1. Further, we reveal that Ad4BP/SF-1 regulates Hummr, a candidate mediator of cholesterol transport from endoplasmic reticula to mitochondria. Given that cholesterol is the starting material for steroidogenesis and is synthesized from acetyl-CoA, which partly originates from glucose, our results suggest that multiple biological processes involved in synthesizing steroid hormones are governed by Ad4BP/SF-1. To our knowledge, this study provides the first example where housekeeping and cell-specific metabolism are coordinated at the transcriptional level.This work was supported by Grants 16H05142 (K.M.), 17H06427 (K.M.), 16K08593 (T.B.), and 17J03270 (M.I.) from the Japan Society for the Promotion of Science (JSPS) KAKENHI; The Uehara Memorial Foundation (K.M.); Takeda Science Foundation (T.B.); The Shin-Nihon of Advanced Medical Research (T.B.).Supplementary information accompanies this paper at https://doi.org/10.1038/s42003-018-0020-z

L-NAME誘発性高血圧ラットの血圧に対する亜硝酸塩とニフェジピンの相互作用

食品成分で血管拡張作用を示す一酸化窒素（NO）を産生する亜硝酸塩と臨床的に汎用されているジヒドロピリミジン系のカルシウム拮抗薬の併用投与による血圧と、それぞれの成分の体内動態に対する相互作用について検討した。SD系雄性ラットに一酸化窒素合成阻害剤（L-NAME）を3 週間投与し、内因性NO産生不足高血圧ラットを作成した。本ラットに亜硝酸塩（経口投与）とニフェジピン（腹腔内投与）を単独、または併用投与し60分間の血圧を測定した。さらに、血液中の亜硝酸イオンと硝酸イオン量、およびニフェジピン濃度をHPLC法により測定した。その結果、血圧は両成分とも投与量依存的な効果を示し、併用投与では血圧降下作用が増強した。その際の、血中ニフェジピン濃度は単独と併用で有意差を認めなかった。しかし、血漿中の亜硝酸イオンは単独に比べ併用投与でTmaxの遅延とCmaxの増加が認められた。以上のことから、亜硝酸塩とニフェジピンの併用は血圧に対して相互作用を示すことが明らかになった。また、この相互作用はニフェジピンが亜硝酸塩（または、亜硝酸塩から生成されたNO）の代謝や消失に影響を与えたことによる薬物動態学的な相互作用であることが示唆された

Radiation Exposure from CT Examinations in Japan

<p>Abstract</p> <p>Background</p> <p>Computed tomography (CT) is the largest source of medical radiation exposure to the general population, and is considered a potential source of increased cancer risk. The aim of this study was to assess the current situation of CT use in Japan, and to investigate variations in radiation exposure in CT studies among institutions and scanners.</p> <p>Methods</p> <p>Data-sheets were sent to all 126 hospitals and randomly selected 14 (15%) of 94 clinics in Gunma prefecture which had CT scanner(s). Data for patients undergoing CT during a single month (June 2008) were obtained, along with CT scan protocols for each institution surveyed. Age and sex specific patterns of CT examination, the variation in radiation exposure from CT examinations, and factors which were responsible for the variation in radiation exposure were determined.</p> <p>Results</p> <p>An estimated 235.4 patients per 1,000 population undergo CT examinations each year, and 50% of the patients were scanned in two or more anatomical locations in one CT session. There was a large variation in effective dose among hospitals surveyed, particularly in lower abdominal CT (range, 2.6-19.0 mSv). CT examinations of the chest and upper abdomen contributed to approximately 73.2% of the collective dose from all CT examinations. It was estimated that in Japan, approximately 29.9 million patients undergo CT annually, and the estimated annual collective effective dose in Japan was 277.4 *10³Sv person. The annual effective dose per capita for Japan was estimated to be 2.20 mSv.</p> <p>Conclusions</p> <p>There was a very large variation in radiation exposure from CT among institutions surveyed. CT examinations of the chest and upper abdomen were the predominant contributors to the collective dose.</p

Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies

Objectives: The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. Background: Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ∼10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. Methods: The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. Results: Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. Conclusions: This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data

The Y Chromosome That Lost the Male-Determining Function Behaves as an X Chromosome in the Medaka Fish, Oryzias latipes

The medaka, Oryzias latipes, has an XX/XY sex-determination system, and a Y-linked DM-domain gene, DMY, is the sex-determining gene in this species. Since DMY appears to have arisen from a duplicated copy of the autosomal DMRT1 gene ∼10 million years ago, the medaka Y chromosome is considered to be one of the youngest male-determining chromosomes in vertebrates. In the screening process of sex-reversal mutants from wild populations, we found a population that contained a number of XY females. PCR, direct sequencing, and RT–PCR analyses revealed two different null DMY mutations in this population. One mutation caused loss of expression during the sex-determining period, while the other comprised a large deletion in putative functional domains. YY females with the mutant-type DMY genes on their Y chromosomes were fully fertile, indicating that the X and Y chromosomes were functionally the same except for the male-determining function. In addition, we investigated the frequencies of the sex chromosome types in this population over four successive generations. The Y chromosomes bearing the mutant-type DMY genes were detected every year with no significant differences in their frequencies. These results demonstrate that aberrant Y chromosomes behaving as X chromosomes have been maintained in this population

Pressure-volume-temperature relationships of trimethoxymethylsilane and tetramethyl orthosilicate at temperatures ranging from 303.2 to 363.2 K and pressures up to 160 MPa

The pressure-volume-temperature (PVT) relationships for trimethoxymethylsilane (MTMS, CH3(CH3O)3Si) and tetramethyl orthosilicate (TMOS, (CH3O)4Si) were measured at temperatures ranging from 303.2 to 363.2 K and pressures up to 160 MPa. Density measurements were carried out with an experimental apparatus based on the variable volume method. The standard uncertainties u(T) = 0.17 K and u(P) = 0.14 MPa, and the relative combined expanded uncertainty Ur (0.95 level of confidence) were Ur(ρ) = (0.0016 and 0.0022) for MTMS and TMOS, respectively. The obtained PVT relationships were correlated using the Tait equation and the Sanchez-Lacombe equation of state to determine the characteristic parameters