Hormone replacement therapy enhances IGF-1 signaling in skeletal muscle by diminishing miR-182 and miR-223 expressions: a study on postmenopausal monozygotic twin pairs

MiRNAs are fine-tuning modifiers of skeletal muscle regulation, but knowledge of their hormonal control is lacking. We used a co-twin case-control study design, that is, monozygotic postmenopausal twin pairs discordant for estrogen-based hormone replacement therapy (HRT) to explore estrogen-dependent skeletal muscle regulation via miRNAs. MiRNA profiles were determined from vastus lateralis muscle of nine healthy 54-62-years-old monozygotic female twin pairs discordant for HRT (median 7 years). MCF-7 cells, human myoblast cultures and mouse muscle experiments were used to confirm estrogen's causal role on the expression of specific miRNAs, their target mRNAs and proteins and finally the activation of related signaling pathway. Of the 230 miRNAs expressed at detectable levels in muscle samples, qPCR confirmed significantly lower miR-182, miR-223 and miR-142-3p expressions in HRT using than in their nonusing co-twins. Insulin/IGF-1 signaling emerged one common pathway targeted by these miRNAs. IGF-1R and FOXO3A mRNA and protein were more abundantly expressed in muscle samples of HRT users than nonusers. In vitro assays confirmed effective targeting of miR-182 and miR-223 on IGF-1R and FOXO3A mRNA as well as a dose-dependent miR-182 and miR-223 down-regulations concomitantly with up-regulation of FOXO3A and IGF-1R expression. Novel finding is the postmenopausal HRT-reduced miRs-182, miR-223 and miR-142-3p expression in female skeletal muscle. The observed miRNA-mediated enhancement of the target genes' IGF-1R and FOXO3A expression as well as the activation of insulin/IGF-1 pathway signaling via phosphorylation of AKT and mTOR is an important mechanism for positive estrogen impact on skeletal muscle of postmenopausal women

Effect of the relative shift between the electron density and temperature pedestal position on the pedestal stability in JET-ILW and comparison with JET-C

The electron temperature and density pedestals tend to vary in their relative radial positions, as observed in DIII-D (Beurskens et al 2011 Phys. Plasmas 18 056120) and ASDEX Upgrade (Dunne et al 2017 Plasma Phys. Control. Fusion 59 14017). This so-called relative shift has an impact on the pedestal magnetohydrodynamic (MHD) stability and hence on the pedestal height (Osborne et al 2015 Nucl. Fusion 55 063018). The present work studies the effect of the relative shift on pedestal stability of JET ITER-like wall (JET-ILW) baseline low triangularity (\u3b4) unseeded plasmas, and similar JET-C discharges. As shown in this paper, the increase of the pedestal relative shift is correlated with the reduction of the normalized pressure gradient, therefore playing a strong role in pedestal stability. Furthermore, JET-ILW tends to have a larger relative shift compared to JET carbon wall (JET-C), suggesting a possible role of the plasma facing materials in affecting the density profile location. Experimental results are then compared with stability analysis performed in terms of the peeling-ballooning model and with pedestal predictive model EUROPED (Saarelma et al 2017 Plasma Phys. Control. Fusion). Stability analysis is consistent with the experimental findings, showing an improvement of the pedestal stability, when the relative shift is reduced. This has been ascribed mainly to the increase of the edge bootstrap current, and to minor effects related to the increase of the pedestal pressure gradient and narrowing of the pedestal pressure width. Pedestal predictive model EUROPED shows a qualitative agreement with experiment, especially for low values of the relative shift

Diagnostic measures for sarcopenia and bone mineral density

Currently used diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. These diagnostic measures associate differently to bone mineral density (BMD), as an example of muscle-related clinical outcome. These differences should be taken into account when studying sarcopenia. Introduction: Diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. To understand differences between these measures, we determined the association with respect to whole body BMD, as an example of muscle-related clinical outcome. Methods: In the European cross-sectional study MYOAGE, 178 young (18-30 years) and 274 healthy old participants (69-81 years) were recruited. Body composition and BMD were evaluated using dual-energy X-ray densitometry. Diagnostic measures for sarcopenia were composed of lean mass as percentage of body mass, appendicular lean mass (ALM) as percentage of body mass, ALM divided by height squared (ALM/height2), knee extension torque, grip strength, walking speed, and Timed Up and Go test (TUG). Linear regression models were stratified for sex and age and adjusted for age and country, and body composition in separate models. Results: Lean mass and ALM/height2 were positively associated with BMD (P < 0.001). Significance remained in all sex and age subgroups after further adjustment for fat mass, except in old women. Lean mass percentage and ALM percentage were inversely associated with BMD in old women (P < 0.001). These inverse associations disappeared after adjustment for body mass. Knee extension torque and handgrip strength were positively associated with BMD in all subgroups (P < 0.01), except in old women. Walking speed and TUG were not related to BMD. Conclusions: The associations between diagnostic measures of sarcopenia and BMD as an example of muscle-related outcome vary widely. Differences between diagnostic measures should be taken into account when studying sarcopenia. \ua9 2013 International Osteoporosis Foundation and National Osteoporosis Foundation

ITER fast ion confinement in the presence of the European test blanket module

This paper addresses the confinement of thermonuclear alpha particles and neutral beam injected deuterons in the 15 MA Q = 10 inductive scenario in the presence of the magnetic perturbation caused by the helium cooled pebble bed test blanket module using the vacuum approximation. Both the flat top phase and plasma ramp-up are studied. The transport of fast ions is calculated using the Monte Carlo guiding center orbit-following code ASCOT. A detailed three-dimensional wall, derived from the ITER blanket module CAD data, is used for evaluating the fast ion wall loads. The effect of the test blanket module is studied for both overall confinement and possible hot spots. The study indicates that the test blanket modules do not significantly deteriorate the fast ion confinement

ITER fast ion confinement in the presence of the European test blanket module

This paper addresses the confinement of thermonuclear alpha particles and neutral beam injected deuterons in the 15 MA Q = 10 inductive scenario in the presence of the magnetic perturbation caused by the helium cooled pebble bed test blanket module using the vacuum approximation. Both the flat top phase and plasma ramp-up are studied. The transport of fast ions is calculated using the Monte Carlo guiding center orbit-following code ASCOT. A detailed three-dimensional wall, derived from the ITER blanket module CAD data, is used for evaluating the fast ion wall loads. The effect of the test blanket module is studied for both overall confinement and possible hot spots. The study indicates that the test blanket modules do not significantly deteriorate the fast ion confinement