Ghrelin regulates proliferation and differentiation of osteoblastic cells

Abstract It has previously been reported that growth hormone secretagogues (GHS) may have a role in the regulation of bone metabolism in animals and humans. In this study we evaluated the effect of ghrelin, the endogenous ligand of GHS receptors, on the proliferation rate and on osteoblast activity in primary cultures of rat calvaria osteoblasts. In the same experiments, we compared the effects of ghrelin with those of hexarelin (HEXA) and EP-40737, two synthetic GHS with different characteristics. Both ghrelin and HEXA (10(-11)-10(-8) M) significantly stimulated osteoblast proliferation at low concentrations (10(-10) M). Surprisingly, EP-40737 demonstrated an antiproliferative effect at 10(-9)-10(-8) M, whereas lower concentrations had no effect on cell proliferation. Ghrelin and HEXA significantly increased alkaline phosphatase (ALP) and osteocalcin (OC) production. At variance with these peptides, EP-40737 did not significantly stimulate ALP and OC. The mRNA for GHS-R1a receptors and the corresponding protein were detected in calvarial osteoblasts by RT-PCR and Western blot respectively, indicating that ghrelin and GHS may bind and activate this specific receptor. We conclude that endogenous ghrelin and synthetic GHS modulate proliferation and differentiation of rat osteoblasts, probably by acting on their specific receptor

1D vs. 2D shape selectivity in the crystallization-driven self-assembly of polylactide block copolymers

yes2D materials such as graphene, LAPONITE® clays or molybdenum disulfide nanosheets are of extremely high interest to the materials community as a result of their high surface area and controllable surface properties. While several methods to access 2D inorganic materials are known, the investigation of 2D organic nanomaterials is less well developed on account of the lack of ready synthetic accessibility. Crystallization-driven self-assembly (CDSA) has become a powerful method to access a wide range of complex but precisely-defined nanostructures. The preparation of 2D structures, however, particularly those aimed towards biomedical applications, is limited, with few offering biocompatible and biodegradable characteristics as well as control over self-assembly in two dimensions. Herein, in contrast to conventional self-assembly rules, we show that the solubility of polylactide (PLLA)-based amphiphiles in alcohols results in unprecedented shape selectivity based on unimer solubility. We use log Poct analysis to drive solvent selection for the formation of large uniform 2D diamond-shaped platelets, up to several microns in size, using long, soluble coronal blocks. By contrast, less soluble PLLA-containing block copolymers yield cylindrical micelles and mixed morphologies. The methods developed in this work provide a simple and consistently reproducible protocol for the preparation of well-defined 2D organic nanomaterials, whose size and morphology are expected to facilitate potential applications in drug delivery, tissue engineering and in nanocomposites.University of Warwick, Materials GRP, EPSRC, The Royal Society, ER

A textual analysis of media framing of mass shootings : how characteristics surrounding mass shootings are framed in men's and women's magazines

The present research attempted to build upon mass shooting studies by analyzing how feature-length magazine articles focusing on these events frame the characteristics surrounding mass shootings in men's and women's health and lifestyle magazines. The researcher conducted a qualitative textual analysis of 24 randomly selected feature-length mass shootings articles in print and online issues of Esquire, Cosmopolitan, GQ and Glamour between January 2012-April 2017. The core findings of this research included how mass shootings almost always fall under one of four frames: individual (internal) blame frames, societal (external) blame frames, profiling the shooter, and recovery and mourning. These articles also presented more complex sub-frames. The sub-frames included: symptoms suffered by the shooter, drugs, medication and counseling, identity, and stereotypes, political and institutional failures, access to firearms, military issues, "never saw it coming," slipping through the cracks, and the victims and survivors of mass shootings as well as community togetherness.Dr. Amanda Hinnant, Thesis Supervisor.Includes bibliographical references (pages 77-81)

Synthesis and controlled growth of osmium nanoparticles by electron irradiation

YesWe have synthesised osmium nanoparticles of defined size (1.5–50 nm) on a B- and S-doped turbostratic graphitic structure by electron-beam irradiation of an organometallic osmium complex encapsulated in self-spreading polymer micelles, and characterised them by transmission electron microscopy (TEM), high-resolution TEM (HRTEM), and atomic force microscopy (AFM) on the same grid. Oxidation of the osmium nanoparticles after exposure to air was detected by X-ray photoelectron spectroscopy (XPS).We thank the Leverhulme Trust (Early Career Fellowship No. ECF-2013-414 to NPEB), the University of Warwick (Grant No. RD14102 to NPEB), the ERC (Grant No. 247450 to PJS), and the EPSRC (EP/F034210/1 to PJS). L.M.A.P., J.L., and G.C. acknowledge financial support from the EU through the ERC Consolidator Grant “VISUAL-MS”

Designing organometallic compounds for catalysis and therapy

Bioorganometallic chemistry is a rapidly developing area of research. In recent years organometallic compounds have provided a rich platform for the design of effective catalysts, e.g. for olefin metathesis and transfer hydrogenation. Electronic and steric effects are used to control both the thermodynamics and kinetics of ligand substitution and redox reactions of metal ions, especially Ru II. Can similar features be incorporated into the design of targeted organometallic drugs? Such complexes offer potential for novel mechanisms of drug action through incorporation of outer-sphere recognition of targets and controlled activation features based on ligand substitution as well as metal- and ligand-based redox processes. We focus here on η 6-arene, η 5-cyclopentadienyl sandwich and half-sandwich complexes of Fe II, Ru II, Os II and Ir III with promising activity towards cancer, malaria, and other conditions. © 2012 The Royal Society of Chemistry

Open access simulation toolbox for the grid connection of offshore wind farms using multi-terminal HVDC networks

Decarbonisation of the European electricity system can become dauntingly costly due to transmission and distribution network issues arising from the integration of intermittent renewable generation sources. It is expected that wind energy will be the principal renewable source by 2050 and, as such, a number of initiatives in the academia and in the industry are being carried out to propose solutions to best accommodate the wind resource. This paper presents work carried out by DEMO 1 partners within the EU FP7 project BEST PATHS. A MATLAB/Simulink toolbox consisting of the necessary building blocks for the simulation and integration of offshore wind farms using enabling technologies such as multiterminal high-voltage direct-current grids is presented. To illustrate the toolbox capabilities, a number of system topologies is studied. System performance is assessed and measured against a set of key performance indicators. To ensure knowledge dissemination, the toolbox has been made available as open access in the BEST PATHS project website

Exogenous administration of gangliosides displaces GPI-anchored proteins from lipid microdomains in living cells

Exogenous application of gangliosides to cells affects many cellular functions. We asked whether these effects could be attributed to the influence of gangliosides on the properties of sphingolipid-cholesterol microdomains on the plasma membrane, also termed rafts. The latter are envisaged as lateral assemblies of sphingolipids (including gangliosides), cholesterol, and a specific set of proteins. Rafts have been implicated in processes such as membrane trafficking, signal transduction, and cell adhesion. Recently, using a chemical cross-linking approach with Madin-Darby canine kidney (MDCK) cells permanently expressing a GPI-anchored form of growth hormone decay accelerating factor (GH-DAF) as a model system, we could show that GPI-anchored proteins are clustered in rafts in living cells. Moreover, this clustering was dependent on the level of cholesterol in the cell. Here we show that incubation of MDCK cells with gangliosides abolished subsequent chemical cross-linking of GH-DAF. Furthermore, insertion of gangliosides into the plasma membrane of MDCK GH-DAF cells renders GH-DAF soluble when subjected to extraction with Triton X-114 at 4 degrees C. Our data suggest that exogenous application of gangliosides displaces GPI-anchored proteins from sphingolipid-cholesterol microdomains in living cells

Barley beta-glucan promotes MnSOD expression and enhances angiogenesis under oxidative microenvironment

Manganese superoxide dismutase (MnSOD), a foremost antioxidant enzyme, plays a key role in angiogenesis. Barley-derived (1.3) β-d-glucan (β-d-glucan) is a natural water-soluble polysaccharide with antioxidant properties. To explore the effects of β-d-glucan on MnSOD-related angiogenesis under oxidative stress, we tested epigenetic mechanisms underlying modulation of MnSOD level in human umbilical vein endothelial cells (HUVECs) and angiogenesis in vitro and in vivo. Long-term treatment of HUVECs with 3% w/v β-d-glucan significantly increased the level of MnSOD by 200% ± 2% compared to control and by 50% ± 4% compared to untreated H2O2-stressed cells. β-d-glucan-treated HUVECs displayed greater angiogenic ability. In vivo, 24 hrs-treatment with 3% w/v β-d-glucan rescued vasculogenesis in Tg (kdrl: EGFP) s843Tg zebrafish embryos exposed to oxidative microenvironment. HUVECs overexpressing MnSOD demonstrated an increased activity of endothelial nitric oxide synthase (eNOS), reduced load of superoxide anion (O2-) and an increased survival under oxidative stress. In addition, β-d-glucan prevented the rise of hypoxia inducible factor (HIF)1-α under oxidative stress. The level of histone H4 acetylation was significantly increased by β-d-glucan. Increasing histone acetylation by sodium butyrate, an inhibitor of class I histone deacetylases (HDACs I), did not activate MnSOD-related angiogenesis and did not impair β-d-glucan effects. In conclusion, 3% w/v β-d-glucan activates endothelial expression of MnSOD independent of histone acetylation level, thereby leading to adequate removal of O2-, cell survival and angiogenic response to oxidative stress. The identification of dietary β-d-glucan as activator of MnSOD-related angiogenesis might lead to the development of nutritional approaches for the prevention of ischemic remodelling and heart failure