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Discounting is a behavioral phenomenon in which the value of an outcome diminishes as a function of its increased delay or decreased probability and is related to substance abuse research because of its theoretical ties with behavioral models of impulsive choice. Research to date suggests that hypothetical outcomes used in discounting research yield data that are indistinguishable from those using potentially real outcomes. However, the extant literature focuses primarily on delay discounting in non-drug-using humans and has not examined whether hypothetical outcomes yield disproportionate numbers of nonsystematic response patterns. In two experiments, we compared hypothetical and potentially real monetary outcomes in delay and probability discounting tasks in terms of rates of discounting and the frequency of nonsystematic response patterns. In Experiment 1, 61 adults reported no smoking, binge drinking, or illicit drug use in the past year. Experiment 2 included a community sample of nicotine-dependent adults (N = 36). In both experiments, discounting for hypothetical and potentially real outcomes yielded similar data, replicating and extending a growing literature pointing to the empirical equivalence of these outcomes. These findings are relevant to research on discounting that is frequently used in the study of substance use and other impulse-control behaviors., ((c) 2011 APA, all rights reserved.)

Autoimmune diseases are prevalent and often life-threatening syndromes, yet the pathogenic triggers and mechanisms involved remain mostly unresolved. Protein asparagine linked- (N-) glycosylation produces glycan structures that substantially differ among the extracellular compartments of evolutionarily divergent organisms. Alpha-mannosidase-II (alphaM-II) deficiency diminishes complex-type N-glycan branching in vertebrates and induces an autoimmune disease in mice similar to human systemic lupus erythematosus. We found that disease pathogenesis provoking glomerulonephritis and kidney failure was nonhematopoietic in origin, independent of complement C3 and the adaptive immune system, mitigated by intravenous administration of immunoglobulin-G, and linked to chronic activation of the innate immune system. N-glycans produced in alphaM-II deficiency bear immune-stimulatory mannose-dependent ligands for innate immune lectin receptors, disrupting the phylogenic basis of this glycomic recognition mechanism. Thus, mammalian N-glycan branching safeguards against the formation of an endogenous immunologic signal of nonself that can provoke a sterile inflammatory response in the pathogenesis of autoimmune disease.

Notch signaling controls formation of joints at leg segment borders and growth of the developing Drosophila leg. Here, we identify the odd-skipped gene family as a key group of genes that function downstream of the Notch receptor to promote morphological changes associated with joint formation during leg development. odd, sob, drm, and bowl are expressed in a segmental pattern in the developing leg, and their expression is regulated by Notch signaling. Ectopic expression of odd, sob, or drm can induce invaginations in the leg disc epithelium and morphological changes in the adult leg that are characteristic of endogenous invaginating joint cells. These effects are not due to an alteration in the expression of other genes of the developing joint. While odd or drm mutant clones do not affect leg segmentation, and thus appear to act redundantly, bowl mutant clones do perturb leg development. Specifically, bowl mutant clones result in a failure of joint formation from the distal tibia to tarsal segment 5, while more proximal clones cause melanotic protrusions from the leg cuticle. Together, these results indicate that the odd-skipped family of genes mediates Notch function during leg development by promoting a specific aspect of joint formation, an epithelial invagination. As the odd-skipped family genes are involved in regulating cellular morphogenesis during both embryonic segmentation and hindgut development, we suggest that they may be required in multiple developmental contexts to induce epithelial cellular changes.