Mutation of the palmitoylation site of estrogen receptor alpha in vivo reveals tissue-specific roles for membrane versus nuclear actions

Estrogen receptor alpha (ERalpha) activation functions AF-1 and AF-2 classically mediate gene transcription in response to estradiol (E2). A fraction of ERalpha is targeted to plasma membrane and elicits membrane-initiated steroid signaling (MISS), but the physiological roles of MISS in vivo are poorly understood. We therefore generated a mouse with a point mutation of the palmitoylation site of ERalpha (C451A-ERalpha) to obtain membrane-specific loss of function of ERalpha. The abrogation of membrane localization of ERalpha in vivo was confirmed in primary hepatocytes, and it resulted in female infertility with abnormal ovaries lacking corpora lutea and increase in luteinizing hormone levels. In contrast, E2 action in the uterus was preserved in C451A-ERalpha mice and endometrial epithelial proliferation was similar to wild type. However, E2 vascular actions such as rapid dilatation, acceleration of endothelial repair, and endothelial NO synthase phosphorylation were abrogated in C451A-ERalpha mice. A complementary mutant mouse lacking the transactivation function AF-2 of ERalpha (ERalpha-AF2(0)) provided selective loss of function of nuclear ERalpha actions. In ERalpha-AF2(0), the acceleration of endothelial repair in response to estrogen-dendrimer conjugate, which is a membrane-selective ER ligand, was unaltered, demonstrating integrity of MISS actions. In genome-wide analysis of uterine gene expression, the vast majority of E2-dependent gene regulation was abrogated in ERalpha-AF2(0), whereas in C451A-ERalpha it was nearly fully preserved, indicating that membrane-to-nuclear receptor cross-talk in vivo is modest in the uterus. Thus, this work genetically segregated membrane versus nuclear actions of a steroid hormone receptor and demonstrated their in vivo tissue-specific roles

Overturning established chemoselectivities : selective reduction of arenes over malonates and cyanoacetates by photoactivated organic electron donors

The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate-metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates

INFLUENCE DU LACTATE ET DU NAD SUR LE TRANSPORT DU GLUCOSE PAR L'INTESTIN RETOURNÉ DE RAT

International audienc

Performance versus values in sustainability transformation of food systems

Questions have been raised on what role the knowledge provided by sustainability science actually plays in the transition to sustainability and what role it may play in the future. In this paper we investigate different approaches to sustainability transformation of food systems by analyzing the rationale behind transformative acts-the ground that the direct agents of change act upon- and how the type of rationale is connected to the role of research and how the agents of change are involved. To do this we employ Max Weber’s distinction between instrumental rationality and value-rationality in social action. In particular, we compare two different approaches to the role of research in sustainability transformation: (1) Performance-based approaches that measure performance and set up sustainability indicator targets and benchmarks to motivate the agents in the food system to change; (2) Values-based approaches that aim at communicating and mediating sustainability values to enable coordinated and cooperative action to transform the food system. We identify their respective strengths and weaknesses based on a cross-case analysis of four cases, and propose that the two approaches, like Weber’s two types of rationality, are complementary-because they are based on complementary observer stances—and that an optimal in-between approach therefore cannot be found. However, there are options for reflexive learning by observing one perspective-and its possible blind spots-from the vantage point of the other, so we suggest that new strategies for sustainability transformation can be found based on reflexive rationality as a third and distinct type of rationalit

Turn by Turn Profile Monitors for the CERN SPS and LHC

In order to preserve the transverse beam emittance along the acceleration chain it is important that the optics of the transfer lines is perfectly matched to the optics of the rings. Special monitors capable of measuring the beam profiles with a turn by turn resolution are very helpful in this respect. A new type of matching monitor has been developed at CERN for the SPS and LHC machines. This monitor relies on imaging OTR light by means of a fast line scan CMOS and an asymmetric optical system based on cylindrical lenses. This contribution describes the design of this monitor, presents the results obtained during the 2012-13 run and outlines the plans for further improving the design