Function and regulation of Rnd proteins in cortical projection neuron migration

The mammalian cerebral cortex contains a high variety of neuronal subtypes that acquire precise spatial locations and form long or short-range connections to establish functional neuronal circuits. During embryonic development, cortical projection neurons are generated in the areas lining the lateral ventricles and they subsequently undergo radial migration to reach the position of their final maturation within the cortical plate. The control of the neuroblast migratory behavior and the coordination of the migration process with other neurogenic events such as cell cycle exit, differentiation and final maturation are crucial to normal brain development. Among the key regulators of cortical neuron migration, the small GTP binding proteins of the Rho family and the atypical Rnd members play important roles in integrating intracellular signaling pathways into changes in cytoskeletal dynamics and motility behavior. Here we review the role of Rnd proteins during cortical neuronal migration and we discuss both the upstream mechanisms that regulate Rnd protein activity and the downstream molecular pathways that mediate Rnd effects on cell cytoskeleton

Oxygen Tension Modulates Neurite Outgrowth in PC12 Cells Through A Mechanism Involving HIF and VEGF

Cell-based approaches are a promising therapeutic strategy for treating injuries to the nervous system, but the optimal means to promote neurite extension and direct cellular behavior are unclear. Previous studies have examined the behavior of neural-like cells in ambient air (21% oxygen tension), yet these conditions are not representative of the physiological oxygen microenvironment of neural tissues. We hypothesized that neuronal differentiation of a model neural cell line (PC12) could be controlled by modulating local oxygen tension. Compared to ambient conditions, PC12 cells cultured in reduced oxygen exhibited significant increases in neurite extension and total neurite length, with 4% oxygen yielding the highest levels of both indicators. We confirmed neurite extension was mediated through oxygen-responsive mechanisms using small molecules that promote or inhibit HIF-1α stabilization. The hypoxic target gene Vegf was implicated as a neurotrophic factor, as neurite formation at 21% oxygen was mimicked with exogenous VEGF, and a VEGF-neutralizing antibody attenuated neurite formation under reduced oxygen conditions. These findings demonstrate that behavior of neural-like cells is driven by the oxygen microenvironment via VEGF function, and suggest promising approaches for future applications in neural repair

Betacellulin inhibits osteogenic differentiation and stimulates proliferation through HIF-1α

Cellular signaling via epidermal growth factor (EGF) and EGF-like ligands can determine cell fate and behavior. Osteoblasts, which are responsible for forming and mineralizing osteoid, express EGF receptors and alter rates of proliferation and differentiation in response to EGF receptor activation. Transgenic mice over-expressing the EGF-like ligand betacellulin (BTC) exhibit increased cortical bone deposition; however, because the transgene is ubiquitously expressed in these mice, the identity of cells affected by BTC and responsible for increased cortical bone thickness remains unknown. We have therefore examined the influence of BTC upon mesenchymal stem cell (MSC) and pre-osteoblast differentiation and proliferation. BTC decreases the expression of osteogenic markers in both MSCs and pre-osteoblasts; interestingly, increases in proliferation require hypoxia-inducible factor-alpha (HIF-α), as an HIF antagonist prevents BTC-driven proliferation. Both MSCs and pre-osteoblasts express EGF receptors ErbB1, ErbB2, and ErbB3, with no change in expression under osteogenic differentiation. These are the first data that demonstrate an influence of BTC upon MSCs and the first to implicate HIF-α in BTC-mediated proliferation

Method for the prediction of nuclear waste solution decontamination by coprecipitation of strontium ions with barium sulphate using the experimental data obtained in non-radioactive environment

International audienceThe theoretical and experimental prediction of the decontamination factor during the treatment of nuclear waste solutions is generally a cumbersome problem due to their complex composition and extremely dangerous environment. Here, a methodology is proposed and experimentally validated allowing the prediction of the decontamination factor by carrying out experiments in small pilot installations in non-radioactive environment. These experiments provide the population density and the crystal growth data of the coprecipitating agent which serve for calculations according to the general relation presented in this paper

Modeling and Comparison of Continuous and Semi-Continuous Processes for Simulating Decontamination of Liquid Nuclear Wastes by the Coprecipitation of Strontium Ions with Barium Sulphate

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Rnd3 coordinates early steps of cortical neurogenesis through actin-dependent and-independent mechanisms

The generation of neurons by neural stem cells is a highly choreographed process that requires extensive and dynamic remodelling of the cytoskeleton at each step of the process. The atypical RhoGTPase Rnd3 is expressed by progenitors in the embryonic brain but its role in early steps of neurogenesis has not been addressed. Here we show that silencing Rnd3 in the embryonic cerebral cortex interferes with the interkinetic nuclear migration of radial glial stem cells, disrupts their apical attachment and modifies the orientation of their cleavage plane. These defects are rescued by co-expression of a constitutively active form of cofilin, demonstrating that Rnd3-mediated disassembly of actin filaments coordinates the cellular behaviour of radial glial. Rnd3 also limits the divisions of basal progenitors via a distinct mechanism involving the suppression of cyclin D1 translation. Interestingly, although Rnd3 expression is controlled transcriptionally by Ascl1, this proneural factor is itself required in radial glial progenitors only for proper orientation of cell divisions

Rare earth recovery and separation using diglycolamides

International audienceRare earth elements (REE) have become essential for our modern economy, in relation to the development of new energy and communication technologies. Depending on their technical-economic efficiency and environmental footprint, hydrometallurgical processes enabling the recovery of separated elements could be of particular interest.Typically these processes include a first pre-treatment (crushing, milling and sieving) and an acidic leaching step (with eventual selective precipitation sub-steps), followed by a solvent extraction (SX) step aimed at the separation and purification of REE. Recently, diglycolamides (DGA) appeared as a very interesting group of extractants for the selective recovery of trivalent REE from nitric acid solutions, particularly in the presence of transition metal ions commonly found in various waste products. In this work, the TODGA extractant was successfully used for designing an efficient REE recovery process. The process integrates the mechanical and physico-chemical treatment of waste, followed by a solvent extraction step for the recovery and intra-separation of REE. Based on the experimental batch data, a phenomenological model has been elaborated taking into account the various distribution equilibria. The model has been implemented in our simulation code and used for calculation of various flowsheets, which have been tested at our pilot facility using compact continuous counter-current mixer-settlers. Experimental SX and modeling data allowing the recovery of >99.95% pure Dysprosium solution will be discussed in this paper. Preliminary technical-economic assessment and life-cycle analysis have also been conducted. Following this first successful demonstration, several novel dissymmetrical DGA have been developed and their solvent extraction behaviour in different acid media has been studied. Indeed, most processes use symmetrical DGA such as TODGA. The present work improves upon the classic design and demonstrates that novel dissymmetrical extractants display a remarkable improvement on REE extraction efficiency compared to reference TODGA in various acid media. Furthermore, the REE separation factors towards major impurities such as Fe3+ are substantially enhanced.The development of novel DGA with increased efficiency paves the way for the recovery and separation of high value REE from different streams. This opens new market opportunities since the effluent treatment has often an important impact either in the CAPEX or the OPEX of a solvent extraction plant. With some DGA extractants adapted to sulfuric acid media, the resulting effluent treatment plant could be cheaper than it would be using nitric acid media. Furthermore, their enhanced performance at low concentration should reduce the price of reagents in the OPEX