(Pro)renin receptor and V-ATPase: from Drosophila to humans

A decade ago, the (P)RR [(pro)renin receptor] was discovered and depicted as a potential activator of the tissue renin-angiotensin system. For this reason, the role of the (P)RR in cardiovascular diseases and diabetes has been particularly studied. However, the discovery of embryonic lethality after (P)RR gene deletion in mouse and zebrafish paved the way for additional roles of (P)RR in cell homoeostasis. Indeed, the (P)RR has been shown to associate with vacuolar H+-ATPase, hence its other name ATP6ap2. Developmental studies in Xenopus and Drosophila have revealed an essential role of this association to promote the canonical and non-canonical Wnt signalling pathways, whereas studies with tissue-specific gene deletion have pointed out a role in autophagy. The present review aims to summarize recent findings on the cellular functions of (P)RR emerging from various mutated and transgenic animal models

Prototype 9.7 m Schwarzschild-Couder telescope for the Cherenkov Telescope Array: status of the optical system

The Cherenkov Telescope Array (CTA) is an international project for a next-generation ground-based gamma ray observatory, aiming to improve on the sensitivity of current-generation experiments by an order of magnitude and provide energy coverage from 30 GeV to more than 300 TeV. The 9.7m Schwarzschild-Couder (SC) candidate medium-size telescope for CTA exploits a novel aplanatic two-mirror optical design that provides a large field of view of 8 degrees and substantially improves the off-axis performance giving better angular resolution across all of the field of view with respect to single-mirror telescopes. The realization of the SC optical design implies the challenging production of large aspherical mirrors accompanied by a submillimeter-precision custom alignment system. In this contribution we report on the status of the implementation of the optical system on a prototype 9.7 m SC telescope located at the Fred Lawrence Whipple Observatory in southern Arizona.Comment: Proceedings of the 35th International Cosmic Ray Conference (ICRC 2017), Busan, Korea. All CTA contributions at arXiv:1709.0348

AMPK alpha 1-induced RhoA phosphorylation mediates vasoprotective effect of estradiol

OBJECTIVE: Estradiol (E2) mediates numerous beneficial effects assigned to estrogens, but whereas mechanisms have been described at the endothelial level, direct effects on vascular smooth muscle cells (VSMC) are poorly documented. As evidence accumulates regarding the role of RhoA in vascular pathophysiology and the benefit of RhoA-Rho associated protein kinase (Rock) pathway inhibition, we analyzed if E2 could inhibit it in VSMC. METHODS AND RESULTS: We show that in VSMC, E2 inhibits the RhoA-Rock pathway in a time- and concentration-dependent manner. The inhibition of RhoA-Rock pathway results from E2-induced phosphorylation of the Ser188 of RhoA. Using pharmacological, transfection, and in vitro phosphorylation experiments, we demonstrate that AMP-activated protein kinase subunit alpha 1 (AMPKalpha1) is activated by estrogen receptor stimulation and catalyzes RhoA phosphorylation induced by E2. Ex vivo, ovariectomy leads to an increase in the amplitude of phenylephrine- or serotonine-induced contractions of aortic rings in wild-type mice but not in AMPKalpha1-knock-out mice or E2-supplemented animals. These functional effects were correlated with a reduced level of RhoA phosphorylation in the aorta of ovariectomized female, male, and AMPKalpha1 knock-out mice. CONCLUSION: Our work thus defines AMPKalpha1 as (1) a new kinase for RhoA and (2) a new mediator of the vasoprotective effects of estrogen

EGF controls the in vivo developmental potential of a mammary epithelial cell line possessing progenitor properties

The bilayered mammary epithelium comprises a luminal layer of secretory cells and a basal layer of myoepithelial cells. Numerous data suggest the existence of self-renewing, pluripotent mammary stem cells; however, their molecular characteristics and differentiation pathways are largely unknown. BC44 mammary epithelial cells in culture, display phenotypic characteristics of basal epithelium, i.e., express basal cytokeratins 5 and 14 and P-cadherin, but no smooth muscle markers. In vivo, after injection into the cleared mammary fat pad, these cells gave rise to bilayered, hollow, alveolus-like structures comprising basal cells expressing cytokeratin 5 and luminal cells positive for cytokeratin 8 and secreting β-casein in a polarized manner into the lumen. The persistent stimulation of EGF receptor signaling pathway in BC44 cells in culture resulted in the loss of the in vivo morphogenetic potential and led to the induction of active MMP2, thereby triggering cell scattering and motility on laminin 5. These data (a) suggest that BC44 cells are capable of asymmetric division for self-renewal and the generation of a differentiated progeny restricted to the luminal lineage; (b) clarify the function of EGF in the control of the BC44 cell phenotypic plasticity; and (c) suggest a role for this phenomenon in the mammary gland development

How To Make A Pie: Reproducible Research for Empirical Economics & Econometrics

Empirical economics and econometrics (EEE) research now relies primarily on the application of code to datasets. Handling the workflow linking datasets, programs, results and finally manuscript(s) is essential if one wish to reproduce results, which is now increasingly required by journals and institutions. We underline here the importance of “reproducible research” in EEE and suggest three simple principles to follow. We illustrate these principles with good habits and tools, with particular focus on their implementation in most popular software and languages in applied economics