Two experiments asked whether resistance to change depended on variable-ratio as opposed to variable-interval contingencies of reinforcement and the different response rates they establish. In Experiment 1, pigeons were trained on multiple random-ratio random-interval schedules with equated reinforcer rates. Baseline response rates were disrupted by intercomponent food, extinction, and prefeeding. Resistance to change relative to baseline was greater in the interval component, and the difference was correlated with the extent to which baseline response rates were higher in the ratio component. In Experiment 2, pigeons were trained on multiple variable-ratio variable-interval schedules in one half of each session and on concurrent chains in the other half in which the terminal links corresponded to the multiple-schedule components. The schedules were varied over six conditions, including two with equated reinforcer rates. In concurrent chains, preference strongly overmatched the ratio of obtained reinforcer rates. In multiple schedules, relative resistance to response-independent food during intercomponent intervals, extinction, and intercomponent food plus extinction depended on the ratio of obtained reinforcer rates but was less sensitive than was preference. When reinforcer rates were similar, both preference and relative resistance were greater for the variable-interval schedule, and the differences were correlated with the extent to which baseline response rates were higher on the variable-ratio schedule, confirming the results of Experiment 1. These results demonstrate that resistance to change and preference depend in part on response rate as well as obtained reinforcer rate, and challenge the independence of resistance to change and preference with respect to response rate proposed by behavioral momentum theory.
No abstract
A technique for high yield recovery of native, biologically active proteins from preparative polyacrylamide gel slices by reverse polarity elution is described. No apparatus other than the standard slab gel electrophoresis system is required. Several proteins have been recovered in biologically active form at a 90% yield, in quantities ranging from 0.4 mg to 4.2 mg. The method is effective with both small (9,000 dalton) and large (186,000 dalton) polypeptides. Both simple and complex proteins are recovered intact. For example, the copper-zinc and manganese superoxide dismutases from crude soybean extracts are active upon recovery. Similarly, the vitamin D-dependent calcium binding proteins from rat kidney and intestine are isolated by this method in homogeneous, active form.
A great challenge of therapeutic peptides (biologics) is their short half-life. However, biologics can be protected by encapsulation in liposomes used as drug-delivery platforms. Liposomes are typically incorporated into cells by endocytic pathways, which eventually expose therapeutics to favorable proteolytic conditions. To enhance biologics protection, we report the design and characterization of a liposome-protein chimera combining the liposome fusogenic properties of peripheral-membrane protein saposin C, covalently linked to a proapoptotic peptide (the active domain of Bcl-2 protein PUMA). We show by NMR that the saposin C component of the chimera is capable of binding liposomes and that the peptide binds prosurvival Bcl-xL, thus following known PUMA’s mechanism to induce cell death. These results indicate that the function of the individual components is preserved in the chimera. Our results point to a promising twofold strategy for drug delivery to; 1) avoid endocytosis by promoting liposome-membrane fusion, 2) provide additional protection by attachment to a stable, protease-resistant protein, which is a well-known method commonly used to prolong biologics half-life.
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