Ghrelin Stimulation of Growth Hormone-Releasing Hormone Neurons Is Direct in the Arcuate Nucleus

International audienceGhrelin targets the arcuate nucleus, from where growth hormone releasing hormone (GHRH) neurones trigger GH secretion. This hypothalamic nucleus also contains neuropeptide Y (NPY) neurons which play a master role in the effect of ghrelin on feeding. Interestingly, connections between NPY and GHRH neurons have been reported, leading to the hypothesis that the GH axis and the feeding circuits might be co-regulated by ghrelin.Here, we show that ghrelin stimulates the firing rate of identified GHRH neurons, in transgenic GHRH-GFP mice. This stimulation is prevented by growth hormone secretagogue receptor-1 antagonism as well as by U-73122, a phospholipase C inhibitor and by calcium channels blockers. The effect of ghrelin does not require synaptic transmission, as it is not antagonized by gamma-aminobutyric acid, glutamate and NPY receptor antagonists. In addition, this hypothalamic effect of ghrelin is independent of somatostatin, the inhibitor of the GH axis, since it is also found in somatostatin knockout mice. Indeed, ghrelin does not modify synaptic currents of GHRH neurons. However, ghrelin exerts a strong and direct depolarizing effect on GHRH neurons, which supports their increased firing rate. Thus, GHRH neurons are a specific target for ghrelin within the brain, and not activated secondary to altered activity in feeding circuits. These results support the view that ghrelin related therapeutic approaches could be directed separately towards GH deficiency or feeding disorders

Unravelling the WWγWW\gamma and WWZWWZ Vertices at the Linear Collider: νˉνγ\bar{\nu} \nu\gamma and νˉνqˉq\bar{\nu}\nu\bar{q}q final states

We perform a detailed analysis of the processes $e^+e^- \rightarrow \bar{\nu} \nu\gamma$ and $\bar{\nu}\nu\bar{q}q$ at future linear $e^+e^-$ colliders and assess their sensitivity to anomalous gauge boson couplings. We consider center of mass energies $\sqrt{s}=$ 350, 500 and 800 GeV. We demonstrate that significant improvements can be obtained if the phase space information for the cross sections is used maximally. At 800 GeV the parameters $\Delta\kappa_{\gamma}$ and $\lambda_{\gamma}$ can be constrained, at 95\% CL, to about 0.02 and 0.01, while the parameters $\Delta\kappa_Z$, $\lambda_Z$ and $\Delta g_1^Z$ can be probed down to about 0.009, 0.002 and 0.004 respectively. The precision of these measurements is likely to be limited by statistical errors at anticipated luminosities at these energies.Comment: LaTeX, 16 pages, 7 figs (embedded

A velocity map imaging spectrometer for measuring absolute differential cross sections for ion-induced electron emission from molecules

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Searching for Fundamentals and Commonalities of Search

This chapter reports the discussion of a group of mostly behavioral biologists, who at- tempt to put research on search from their own discipline into a framework that might help identify parallels with cognitive search. Essential components of search are a func- tional goal, uncertainty about goal location, the adaptive varying of position, and often a stopping rule. The chapter considers a diversity of cases where search is in domains other than spatial and lists other important dimensions in which search problems differ. One dimension examined in detail is social interactions between searchers and search- ers, targets and targets, and targets and searchers. The producer-scrounger game is pre- sented as an example; despite the extensive empirical and theoretical work on the equi- librium between the strategies, it is largely an open problem how animals decide when to adopt each strategy, and thus how real equilibria are attained. Another dimension that explains some of the diversity of search behavior is the modality of the information utilized (e.g., visual, auditory, olfactory). The chapter concludes by highlighting further parallels between search in the external environment and cognitive search. These sug- gest some novel avenues of research

MITF activity is regulated by a direct interaction with RAF proteins in melanoma cells

International audienceAbstract The MITF transcription factor and the RAS/RAF/MEK/ERK pathway are two interconnected main players in melanoma. Understanding how MITF activity is regulated represents a key question since its dynamic modulation is involved in the phenotypic plasticity of melanoma cells and their resistance to therapy. By investigating the role of ARAF in NRAS-driven mouse melanoma through mass spectrometry experiments followed by a functional siRNA-based screen, we unexpectedly identified MITF as a direct ARAF partner. Interestingly, this interaction is conserved among the RAF protein kinase family since BRAF/MITF and CRAF/MITF complexes were also observed in the cytosol of NRAS-mutated mouse melanoma cells. The interaction occurs through the kinase domain of RAF proteins. Importantly, endogenous BRAF/MITF complexes were also detected in BRAF-mutated human melanoma cells. RAF/MITF complexes modulate MITF nuclear localization by inducing an accumulation of MITF in the cytoplasm, thus negatively controlling its transcriptional activity. Taken together, our study highlights a new level of regulation between two major mediators of melanoma progression, MITF and the MAPK/ERK pathway, which appears more complex than previously anticipated