Structure-Function Studies of the Ribonuclease Inhibitor

Ribonuclease inhibitor (RI) is a cytosolic protein that inhibits the activity of pancreatic-type ribonucleases. The RI:ribonuclease complex is the subject of much research because select ribonucleases, show anti-tumor activity when they are able to escape the inhibitory action of RI. Conversely, angiogenin (ANG), a ribonuclease and potent inducer of angiogenesis, may facilitate tumor metastasis by inducing neovascularization. RI may, in the case of ANG, prove a useful chemotherapeutic agent through the inhibition of angiogenesis. Unfortunately, the oxidation-sensitivity of RI renders it difficult to study in laboratory settings and would limit its efficacy as a pharmaceutical agent for preventing angiogenesis. We attempt to create a variant of RI that resists oxidation, but retains its affinity for pancreatic ribonucleases. The instability of RI in oxidative environments arises from its 32 reduced cysteine residues, each of which must remain reduced for proper functioning of the protein. Therefore, we mutated the cysteine residues to less oxidation-sensitive residues. Based on primary and tertiary structure location, cysteine mutation sites were divided into six groups. RI variants were created based on mutation groups. Analysis of these mutants will allow us to evaluate which, if any, of the positions contribute significantly to the stability of RI or its ability to bind ribonucleases.

Supersymmetric Soliton Dynamics in 2D Curved Space

The aim of this research was to make the supersymmetric extension of a model we built the previous summer that describes the movement of a soliton in AdS2 space. The cosistent algebra for the five generators of supersymmetric (SUSY-ADS2) were determined and transformation rules calculated. Maurer-Cartan one forms were used to calculate a Lagrangian that is invariant under SUSY-ADS22 transformations. The equations of motion were derived and solved using conserved quantities.

Slowly-developing Alterations in Nucleus Accumbens Neuronal Activity

The nucleus accumbens (NAc) is thought to play a prominent role in motivational processes underlying goal-directed behavior. Consistent with this notion, chronic electrophysiological studies monitoring the activity of individual NAc neurons during operant behavior have revealed phasic (rapid) alterations in firing rate tightly correlated with discrete appetitive or consummatory responses in operant behavioral paradigms. However, whether NAc neurons exhibit slowly-developing alterations in firing rate potentially related to motivational state has not been extensively examined. Here we report data from a set of 50 NAc neurons recorded during performance of an operant task involving sucrose reward. Consistent with a recent report (Synapse, 60(6): 420-8), many cells exhibited tonic changes in firing rate that developed slowly over minutes to tens-of-minutes during the behavioral session, and these patterns could often be explained by parallel changes in behavioral response density. However, a small subset of cells exhibited tonic alterations that were independent of observable behavior. These patterns of activity provide a possible substrate for the neural representation of state variables related to motivational state.