Cyclic AMP accumulation alters calmodulin localization in SK-N-SH human neuroblastoma cells

In SK-N-SH human neuroblastoma cells, the muscarinic agonist carbachol promotes polyphosphoinositide (PPI) hydrolysis via M3 receptors and increases cyclic AMP levels through an unidentified mechanism. Activation of PPI hydrolysis by carbachol elicits a robust translocation of CaM from membranes into cytosol which was previously shown to be mimicked by the addition of the calcium ionophore ionomycin and the phorbol ester TPA28. The effect of agonist-stimulated second messenger production on CaM localization was determined by activating receptors that increase and decrease adenylyl cyclase activity on SK-N-SH cells. VIP (10 [mu]M), prostaglandin E1 (30 [mu]M) and forskolin (10 [mu]M) all increased adenylyl cyclase activity 8- to 10-fold above the activity with 1 [mu]M GTP. Carbachol (100 [mu]M) did not stimulate adenylyl cyclase activity. The [alpha]2-adrenergic agonist UK 14,304 (0.1 [mu]M) and the [delta] and [mu] opioid DPDPE (10 [mu]M) and DAMGO (10 [mu]M) inhibited forskolin-stimulated cyclic AMP formation by 27-32%. CaM did not stimulate adenylyl cyclase activity. Incubation of cells with vasoactive intestinal polypeptide (VIP), dibutyryl cyclic AMP and forskolin, resulted in 30% decrease in membrane CaM and an increase in cytosolic CaM of 40-50%. The CaM translocation with the combination of an agent that elevates cyclic AMP levels and a low dose of carbachol was not different from that observed with either agent alone. UK 14,304, DPDPE and DAMGO potentiated carbachol-stimulated increases in cytosolic CaM. Upon the addition of carbachol, a 5-fold increase in intracellular calcium concentration measured with fura-2 fluorescence was observed. VIP and UK 14,304 elevated intracellular calcium concentrations 2 to 3 fold, while forskolin (10 [mu]M) had no effect. Thus, receptor-mediated cyclic AMP synthesis and Ca2+ fluxes alter CaM localization, but with a smaller magnitude than the CaM translocation stimulated by PPI hydrolysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30296/1/0000698.pd

On benevolence and love of others

Hobbes is famous for his insights into the impact of man’s fear, glory and greed on war and peace, not for his views on the bearing of men’s benevolence on the commonwealth. Are Hobbesian people even capable of love of others? In the literature, we find two main answers: one view is that Hobbes ruled out the possibility of disinterested benevolence among men; the other is that Hobbes considered actions driven by genuine benevolence possible but uncommon. After reviewing in broad outlines the two above positions, this chapter seeks to demonstrate the claim that Hobbes did not consider relevant to establish if men are capable of genuine benevolence or not, because he maintained that benevolent men can be as inept as egoists in differentiating apparent and real good for themselves and their loved ones and the effect of misguided altruism on the commonwealth is as damaging as the effect of ill-advised egoism.Postprin

contract Theory in Historical Context: Essays on Grotius, Hobbes, and Locke

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Exploring the Experiences of Adults Participating in Community Circus Classes: The Synergistic Relationship Between Circus and Occupational Therapy

This participant-observer, phenomenological qualitative study explored the adult experience of a community circus class through an occupational therapy lens. Following 4 months of weekly participant-observation, semi-structured interviews were conducted with four adult beginner students in a community-based social circus class. Interviews were audio recorded, transcribed and analyzed using a grounded theory approach to identify six themes. Two themes addressed the structural supports of the class: Meeting People Where They Are , and Culture and Competition. Four themes were based on participant experiences and perceived outcomes: Releasing Expectations, Trying, Learning, and Fun, Making Friends, Making Community, and Feeling Better. Findings suggest that through the fun aspects of circus participation, students were able to confront and overcome physical, social, emotional and cognitive challenges. In this way, personal growth and quality of life were promoted. External supports enabled students to adopt an individualized approach to participation that encouraged self-awareness and self-assessment across multiple domains. Due to the scarcity of research investigating adult participation in circus, the therapeutic benefit of circus participation merits further investigation. Circus and occupational therapy may develop a mutually beneficial relationship on the basis of shared common philosophy and values. By working together, occupational therapy and circus may enhance their ability to address occupational justice, inclusivity, empowerment, connection, play and quality of life