Amino Acid Residues Implicated in the Interaction of Melanocortin Ligands and their Receptors: A Study of MC2R Selectivity

Author: Kristopher D. Veo Title: Amino acid residues implicated in the interaction of Melanocortin ligands and their receptors: A study of MC2R selectivity Advisor: Dr. Robert M. Dores Degree Date: August 2009 ABSTRACT Melanocortin receptor ligand selectivity has been a question not easily answered. The inability to functionally express melanocortin 2 receptor (MC2R) has inhibited the study of why MC2R is only stimulated by ACTH, a melanocortin hormone. With the recent discovery of the MC2R accessory protein (MRAP), creating a heterologous system is now feasible. Using a general cell line like CHO-K1 cells, which do not express endogenous MCRs, we were able to create a heterologous expression system and test the selectivity of MC2R using analog variants of ACTH(1-24). Our results indicate an amino acid requirement in the C-terminal portion of ACTH(1-24) for activation, which supports the 2-step method of activation hypothesized for MC2R. This site, the tetra basic cleavage site, when altered does not stimulate cAMP production and does not compete with ACTH(1-24) for binding. We also demonstrate the potential for a non-mammalian MC2R system in cloning full length Silurana tropicalis MC2R and completed localization studies with this system with MRAP using CHO-K1 cells.

Psychological and Social Perspectives on Malingering and Symptom Exaggeration: Conceptualization and Interventions Using Acceptance and Commitment Therapy

Malingering and the production of false symptoms seen in such disorders as Factitious Disorder are an ongoing mystery to medical and mental health professionals. Historically, these presentations have been difficult to identify and treat. As might be expected, individuals with such symptomology rarely agree to participate in research, possibly because of a reluctance to admit to the feigning or exaggerating behaviors and a fear of reprisals. Many different etiologies have been proposed, including the assumption of roles in order to manage impressions, taking control of symptoms in order to gain attention or other rewards or avoid aversive events, and even the production of symptoms that is largely out of awareness such as is seen in conversion or somatoform presentations. By examining historical and present-day beliefs about etiology and treatment interventions, professionals can explore what new types of effective treatment might look like. The behaviorist philosophy that underlies Acceptance and Commitment Therapy proposes a perspective emphasizing effective working in context. This philosophy also suggests individuals sometimes engage in behavior in order to escape from or avoid aversive experiences. Utilizing case examples and fresh behavioral perspectives provides insight and ideas for conceptualization of these behaviors of interest. Using the above conceptualizations, an ACT based treatment of those who produce false symptoms is introduced.