ADP is the Dominant Controller of AMPactivated Protein Kinase Activity Dynamics in Skeletal Muscle during Exercise

Exercise training elicits profound metabolic adaptations in skeletal muscle cells. A key molecule in coordinating these adaptations is AMP-activated protein kinase (AMPK), whose activity increases in response to cellular energy demand. AMPK activity dynamics are primarily controlled by the adenine nucleotides ADP and AMP, but how each contributes to its control in skeletal muscle during exercise is unclear. We developed and validated a mathematical model of AMPK signaling dynamics, and then applied global parameter sensitivity analyses with data-informed constraints to predict that AMPK activity dynamics are determined principally by ADP and not AMP. We then used the model to predict the effects of two additional direct-binding activators of AMPK, ZMP and Compound 991, further validating the model and demonstrating its applicability to understanding AMPK pharmacology. The relative effects of direct-binding activators can be understood in terms of four properties, namely their concentrations, binding affinities for AMPK, abilities to enhance AMPK phosphorylation, and the magnitudes of their allosteric activation of AMPK. Despite AMP’s favorable values in three of these four properties, ADP is the dominant controller of AMPK activity dynamics in skeletal muscle during exercise by virtue of its higher concentration compared to that of AMP

[map] Congo Belge, carte des précipitations annuelles exprimées en millimètres pour la période 1930-1951 /

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Zinc effect on the primary circuit contamination of a Belgian PWR using the OSCAR V1.3 code

International audienceThe purpose of the OSCAR code, developed by the CEA in collaboration with EDF and AREVA NP, is to simulate the contamination of the PWR (Pressurized Water Reactor) primary system. The OSCAR code, coupled to its chemistry module PHREEQCEA, allows researchers to analyse the corrosion product behaviour and to calculate the volume and surface activities of a primary system. It synthesizes knowledge and allows us to progress in understanding the phenomena involved in the contamination caused by activated corrosion products.The OSCAR V1.3 code has been used to simulate the effect of zinc on the primary circuit contamination of a Belgian PWR operated by ENGIE. This paper highlights the physicochemical phenomena involved during a zinc injection. The OSCAR simulation shows thatZinc precipitates on the inner oxide (Cr-rich layer) instead of cobalt showing that zinc has a better affinity than cobalt with chromites (change in the Co equilibrium concentration).Cobalt concentration and $^{58}$Co and $^{60}$Co activities increase in the primary coolant and on the outer oxide of both the in-core and out-of-core surfaces (Fe-rich layer). Different plants have observed this increase during the first cycles of Zn injection.An antagonist effect exists between the decreasing $^{58}$Co and $^{60}$Co activities of the inner oxide and the increasing activities of the outer oxide, which explains the slight impact of a zinc injection observed by EMECC campaigns

110^{110}mAg behaviour in PWRs Lessons learnt from the EMECC campaigns

International audienceFor 45 years, most of the time in collaboration with EDF, CEA has measured the contamination of PWR circuits by gamma spectrometry using the so-called EMECC device. These measurements allow to determine the surface activities accurately in order to study the behaviour of the activated corrosion products.In case of pollution by $^{110}$mAg, the main lessons learnt from EMECC campaigns and primary coolant filtering campaigns as well are as followsDuring oxygenation, $^{110}$Ag dissolves from the primary surfaces and precipitates on the cold parts of auxiliary systems before dissolving slowly from these cold parts. It leads to a sharp increase of dose rate at the vicinity of the cold parts of auxiliary systems.Because of the precipitation on the Nuclear Sampling System (NSS), 110mAg sampled via the NSS is not representative of the $^{110}$Ag volume activity of the Reactor Coolant System.Under oxidizing and acid conditions, Ag is trapped very well by cation exchange resins. On the other hand, silver is in an insoluble form (colloids) in a reducing medium and it is not trapped by ion exchangers