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- Adlanmerini, M., et al.
(författare)
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Mutation of Arginine 264 on ER alpha (Estrogen Receptor Alpha) Selectively Abrogates the Rapid Signaling of Estradiol in the Endothelium Without Altering Fertility
- 2020
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Ingår i: Arteriosclerosis, Thrombosis, and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 40:9, s. 2143-2158
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Tidskriftsartikel (refereegranskat)abstract
- Objective: ER alpha (estrogen receptor alpha) exerts nuclear genomic actions and also rapid membrane-initiated steroid signaling. The mutation of the cysteine 451 into alanine in vivo has recently revealed the key role of this ER alpha palmitoylation site on some vasculoprotective actions of 17 beta-estradiol (E2) and fertility. Here, we studied the in vivo role of the arginine 260 of ER alpha which has also been described to be involved in its E2-induced rapid signaling with PI-3K (phosphoinositide 3-kinase) as well as G protein in cultured cell lines. Approach and Results: We generated a mouse model harboring a point mutation of the murine counterpart of this arginine into alanine (R264A-ER alpha). In contrast to theC451A-ER alpha, theR264A-ER alpha females are fertile with standard hormonal serum levels and normal control of hypothalamus-pituitary ovarian axis. Although R264A-ER alpha protein abundance was normal, the well-described membrane ER alpha-dependent actions of estradiol, such as the rapid dilation of mesenteric arteries and the acceleration of endothelial repair of carotid, were abrogated inR264A-ER alpha mice. In striking contrast, E2-regulated gene expression was highly preserved in the uterus and the aorta, revealing intact nuclear/genomic actions in response to E2. Consistently, 2 recognized nuclear ER alpha-dependent actions of E2, namely atheroma prevention and flow-mediated arterial remodeling were totally preserved. Conclusions: These data underline the exquisite role of arginine 264 of ER alpha for endothelial membrane-initiated steroid signaling effects of E2 but not for nuclear/genomic actions. This provides the first model of fertile mouse with no overt endocrine abnormalities with specific loss-of-function of rapid ER alpha signaling in vascular functions.
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| 2. |
- Delva, Pacôme, et al.
(författare)
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GENESIS: co-location of geodetic techniques in space
- 2023
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Ingår i: Earth, Planets and Space. - : Springer Science and Business Media LLC. - 1880-5981 .- 1343-8832. ; 75:1
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Tidskriftsartikel (refereegranskat)abstract
- Improving and homogenizing time and space reference systems on Earth and, more specifically, realizing the Terrestrial Reference Frame (TRF) with an accuracy of 1 mm and a long-term stability of 0.1 mm/year are relevant for many scientific and societal endeavors. The knowledge of the TRF is fundamental for Earth and navigation sciences. For instance, quantifying sea level change strongly depends on an accurate determination of the geocenter motion but also of the positions of continental and island reference stations, such as those located at tide gauges, as well as the ground stations of tracking networks. Also, numerous applications in geophysics require absolute millimeter precision from the reference frame, as for example monitoring tectonic motion or crustal deformation, contributing to a better understanding of natural hazards. The TRF accuracy to be achieved represents the consensus of various authorities, including the International Association of Geodesy (IAG), which has enunciated geodesy requirements for Earth sciences. Moreover, the United Nations Resolution 69/266 states that the full societal benefits in developing satellite missions for positioning and Remote Sensing of the Earth are realized only if they are referenced to a common global geodetic reference frame at the national, regional and global levels. Today we are still far from these ambitious accuracy and stability goals for the realization of the TRF. However, a combination and co-location of all four space geodetic techniques on one satellite platform can significantly contribute to achieving these goals. This is the purpose of the GENESIS mission, a component of the FutureNAV program of the European Space Agency. The GENESIS platform will be a dynamic space geodetic observatory carrying all the geodetic instruments referenced to one another through carefully calibrated space ties. The co-location of the techniques in space will solve the inconsistencies and biases between the different geodetic techniques in order to reach the TRF accuracy and stability goals endorsed by the various international authorities and the scientific community. The purpose of this paper is to review the state-of-the-art and explain the benefits of the GENESIS mission in Earth sciences, navigation sciences and metrology. This paper has been written and supported by a large community of scientists from many countries and working in several different fields of science, ranging from geophysics and geodesy to time and frequency metrology, navigation and positioning. As it is explained throughout this paper, there is a very high scientific consensus that the GENESIS mission would deliver exemplary science and societal benefits across a multidisciplinary range of Navigation and Earth sciences applications, constituting a global infrastructure that is internationally agreed to be strongly desirable. Graphical Abstract: [Figure not available: see fulltext.]
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