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

Space demostration of bare electrodynamic tape-tether technology on the sounding rocket S520-25

A spaceflight validation of bare electro dynamic tape tether technology was conducted. A S520-25 sounding rocket was launched successfully at 05:00am on 31 August 2010 and successfully deployed 132.6m of tape tether over 120 seconds in a ballistic flight. The electrodynamic performance of the bare tape tether employed as an atmospheric probe was measured. Flight results are introduced through the present progressive report of the demonstration and the results of flight experiment are examined as the premier report of the international cooperation between Japan, Europe, USA and Australia. Future plans for maturing space tether technology, which will play an important role for future space activities, are also discussed

T-REX: Bare electro-dynamic tape-tether technology experimetn on sounding rocket S520

The project to verify the performance of space tether technology was successfully demonstrated by the launch of the sounding rocket S520 the 25tu. The project is the space demonstration of science and engineering technologies of a bare tape electrodynamic tether (EDT) in the international campaign between Japan, USA, Europe and Australia. Method of "Inverse ORIGAMI (Tape tether folding)" was employed in order to deploy the bare tape EDT in a short period time of the suborbital flight. The deployment of tape tether was tested in a various experimental schemes on ground to show high reliability of tape tether deployment. The rocket was launched on the summer of 2010 and deployed a bare electro-dynamic tape tether with length 132.6 m, which is the world record of the length deployment of tape tether. The verification of tether technology has found a variety kind of science and technology results as the first in the humankind and will lead a large number of applications of space tether technologie

Pick’s Tau Fibril Shows Multiple Distinct PET Probe Binding Sites: Insights from Computational Modelling

In recent years, it has been realized that the tau protein is a key player in multiple neurodegenerative diseases. Positron emission tomography (PET) radiotracers that bind to tau filaments in Alzheimer’s disease (AD) are in common use, but PET tracers binding to tau filaments of rarer, age-related dementias, such as Pick’s disease, have not been widely explored. To design disease-specific and tau-selective PET tracers, it is important to determine where and how PET tracers bind to tau filaments. In this paper, we present the first molecular modelling study on PET probe binding to the structured core of tau filaments from a patient with Pick’s disease (TauPiD). We have used docking, molecular dynamics simulations, binding-affinity and tunnel calculations to explore TauPiD binding sites, binding modes, and binding energies of PET probes (AV-1451, MK-6240, PBB3, PM-PBB3, THK-5351 and PiB) with TauPiD. The probes bind to TauPiD at multiple surface binding sites as well as in a cavity binding site. The probes show unique surface binding patterns, and, out of them all, PM-PBB3 proves to bind the strongest. The findings suggest that our computational workflow of structural and dynamic details of the tau filaments has potential for the rational design of TauPiD specific PET tracers

Pick’s Tau fibril shows multiple distinct PET probe binding sites: Insights from computational modelling

In recent years it has been realized that the tau protein is a key player in multiple neurodegenerative diseases. Positron emission tomography (PET) radiotracers that bind to tau filaments in Alzheimer’s disease (AD) are in common use, but PET tracers binding to tau filaments of rarer, age-related dementias, such as Pick’s disease, have not been explored much. To design disease-specific and tau-selective PET tracers, it is important to determine where and how PET tracers bind to tau filaments. In this paper, we present the first molecular modelling study on PET probe binding to the structured core of tau filaments from a patient with Pick’s disease (TauPiD). We have used docking, molecular dynamics simulations, binding-affinity and tunnel calculations to explore TauPiD binding sites, binding modes, and binding energies of PET probes (AV-1451, MK-6240, PBB3, PM-PBB3, THK-5351 and PiB) with TauPiD. The probes bind to TauPiD at multiple surface binding sites as well as in a cavity binding site. The probes show unique surface binding patterns, and, out of them all, PM-PBB3 proves to bind the strongest. The findings suggest that our computational workflow of structural and dynamic details of the tau filaments has potential for the rational design of TauPiD specific PET tracers

Tau filaments and development of positron emission tomography (PET) tracers

Neurofibrillary lesions strongly correlate with cognitive deficits, making them an important therapeutictarget for Alzheimer’s disease (AD) (1, 2). Dominantly inherited mutations in MAPT, the Taugene, cause a form of frontotemporal dementia that can be associated with parkinsonism (FTDP-17T), showing that dysfunction of Tau protein is sufficient to cause neurodegeneration and dementia(3). In FTDP-17T, abundant filamentous Tau inclusions are present in either nerve cells or in bothnerve cells and glial cells. Aβ deposits, a defining feature of AD, are not characteristic of FTDP-17T.However, there are many similarities between cases of FTDP-17T and other pure Tauopathies, suchas sporadic progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), argyrophilicgrain disease (AGD), and Pick’s disease, especially with regard to the isoform composition of Taufilaments

Tau Filaments and the Development of Positron Emission Tomography Tracers

A pathological pathway leading from soluble, monomeric to insoluble, filamentous Tau, is believed to underlie human Tauopathies. Cases of frontotemporal dementia are caused by dominantly inherited mutations in MAPT, the Tau gene. They show that dysfunction of Tau protein is sufficient to cause neurodegeneration and dementia. Extrapolation to the more common sporadic Tauopathies leads one to conclude that the pathological pathway is central to the development of all cases of disease, even if there are multiple reasons for Tau assembly. These findings are conceptually similar to those reported for beta-amyloid, alpha-synuclein and prion protein. Here, we provide an overview of Tau filaments and their positron emission tomography ligands

Panel Extension Satellite (PETSAT) -A Novel Satellite Concept Consisting of Modular, Functional and Plug-in Panels

Abstract A novel concept of satellite design, named PETSAT, is proposed in this paper. In this concept, a satellite is made of several Functional Panels such as the CPU panel, Battery panel, Communication panel, Attitude control panel, or Thruster panel, each of which has a special dedicated function. By connecting these panels with a reliable connection mechanism in a plug-in fashion, the total integrated system has a full satellite's function. Various combinations of functional panels, (for example, two CPU panels + one communication panels + three attitude control panels + two battery panels, etc.) provide flexibility to deal with various mission requirements, even though the basic panels are the same for various missions. The concept, technical issues and conceptual study results of PETSAT will be discussed

A Novel Satellite Concept “Panel Extension Satellite (PETSAT)” Consisting of Plug-in, Modular, Functional Panels

A novel concept of satellite design, named PETSAT, is proposed in this paper. In this concept, a satellite is made of several Functional Panels such as Communication panel, Attitude control panel, Thruster panel, and “Mission Panel,” each of which has a special dedicated function. By connecting these panels by reliable connection mechanism in plug-in fashion, the total integrated system as a whole has a satellite function. Various combinations of functional panels, (for example, one communication panel + three attitude control panels + two thruster panels, etc.) provide flexibility to deal with various mission requirements, even though the basic panels are the same for various missions. First, PETSAT concept is described and its strong points and shortcomings are discussed. Next, several key technologies are explained in more detail, including panel structures, deployment mechanism, power distribution network, information network architecture and thruster system. Finally the current status of development of SOHLA-2, an in-orbit demonstration satellite for PETSAT concept planned to be launched in 2008-2009, will be briefly described