Synthesis and alkyne-coupling chemistry of cyclomanganated 1- and 3-acetylindoles, 3-formylindole and analogues

The syntheses are reported of new cyclomanganated indole derivatives (1-acetyl-κO-indolyl-κC2)dicarbonylbis(trimethylphosphite)manganese (2), (1-methyl-3-acetyl-κO-indolyl-κC2)tetracarbonylmanganese (4), (3-formyl-κO-indolyl-κC2)tetracarbonylmanganese (5a) and (1-methyl-3-formyl-κO-indolyl-κC2)tetracarbonylmanganese (5b). The unusually complicated crystal structure of 5b has been determined, the first for a cyclomanganated aryl aldehyde. The preparations of a mitomycin-related pyrrolo-indole and related products by thermally promoted and oxidatively (Me3NO) initiated alkyne-coupling reactions of the previously known complex (1-acetyl-κO-indolyl-κC2)tetracarbonylmanganese (1) are reported for different alkynes and solvents. X-ray crystal structures are reported for the dimethyl acetylenedicarboxylate coupling product of 1 (dimethyl 1-methyl-l-hydroxypyrrolo[1,2a]-indole-2,3-dicarboxylate; 6a), and an unusually-cyclised triple insertion product 8 from the coupling of acetylene with 4, in which a cyclopentadiene moiety is η3-allyl-coordinated to Mn through only one double bond and an exocyclic carbon, but which rearranges on heating to an η5-cyclopentadienyl complex

Point mutation of an RGD sequence in the human P2Y2 receptor to a QGD sequence conserves Go-mediated signal transduction

Abstract only availableThe P2Y2 nucleotide receptor is a Go/q coupled receptor that is activated equipotently by extracellular nucleotides such as ATP or UTP and is upregulated in a variety of tissues in response to injury or stress. The biological effects of extracellular nucleotides are mediated through activation of P1 and P2 purinergic receptors. P1 receptors are responsive to adenine and P2 receptors are activated by a variety of nucleotides including ATP and UTP. The P2 receptors are subdivided into two distinct categories, the ionotropic ligand-gated channel (P2X) receptors and G-protein coupled P2Y-receptors, with seven transmembrane domains. Previous studies have shown that the human P2Y2 nucleotide receptor contains an arginine-glycine-aspartic acid (RGD), integrin-binding domain. This domain is located in the first extracellular loop of the receptor and binds specifically to the v3/5 group of integrins. The P2Y2 receptor interacts with the v integrins by the RGD domain to activate Go and induce cell migration. The human and murine P2Y2R's have the RGD integrin-binding domain, whereas the rat homologue has a QGD domain. However, this change in the arginine position in the RGD integrin-binding domain is considered to be a conservative substitution that maintains integrin binding. In order to confirm this assumption we changed the RGD domain of the human P2Y2 receptor into the QGD domain by in vitro mutagenesis. The wild-type and the QGD mutant P2Y2 receptors were transiently transfected into P2 receptor null, 1321 N1 astrocytoma cell line. Preliminary data suggest that the QGD mutant can stimulate PLC dependent intracellular Ca2+ mobilization and also activate cofillin and extracellular signal-regulated kinases (Erk) with equal efficacy and agonist potency as the wild type receptor. Further tests need to be done to verify that integrin bindin and signaling by the Rac and Rho pathways remain unaffected in the QGD mutant to induce integrin dependent cell migration in response to UTP and ATP.NSF-REU Program in Biological Sciences & Biochemistr

An approach to treating depressive and psychotic illness in Indigenous communities.

This study is one of the activities of a multi-site research program, the Australian Mental Health Initiative (AIMhi), funded by the National Health and Medical Research Council. AIMhi in the Northern Territory collaborated with Aboriginal mental health workers and Northern Territory remote service providers in developing a range of resources and strategies to promote improved Indigenous mental health outcomes. A brief intervention that combines the principles of motivational interviewing, problem solving therapy and chronic disease self-management is described. The intervention has been integrated into a randomised controlled trial. Early findings suggest that the strategy and its components are well received by clients with chronic mental illness, and their carers, in remote communities

Management of complex symptoms in multiple sclerosis (MS)

People with MS can present with a complex range of symptoms. Some of these include dysautonomia (autonomic dysfunction), fatigue, cognitive impairment, and mood disorders. These symptoms must be managed in order to optimise intervention outcomes