Stony Brook University

About: Stony Brook University is a education organization based out in Stony Brook, New York, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 32534 authors who have published 68218 publications receiving 3035131 citations. The organization is also known as: State University of New York at Stony Brook & SUNY Stony Brook.

Learned Associations Over Long Delays1

Abstract: Publisher Summary The literature of specific hungers and bait shyness contains much indirect evidence of learning involving prolonged delay of reinforcement. Specific hunger refers to the selective feeding by animals as they learn to correct a specific dietary deficiency, such as thiamine deficiency, while bait shyness describes the rejection of poisoned baits by animals, which have survived a previous poisoning attempt. It seems unlikely that learning can take place at all with delays of more than a few seconds. Instances of learning with protracted delays of reinforcement are always cases where immediate secondary reinforcement occurs. It is generalized that delayed reinforcement is not effective except under elaborate training conditions. However, when the response is ingestion and the rewards or punishments are changes in the physiological state of the organism, this generalization appears to be incorrect. Most specific hungers can be explained in terms of learned associations involving delayed aftereffects; an exception is the specific hunger for sodium, which appears to be largely innate. If rats are subjected to sodium deficiency and recover from it by drinking salt water, they tend to drink an abnormally large amount of salt water after the deficiency is relieved.

NF-κB Signaling: Multiple Angles to Target OA

Abstract: In the context of OA disease, NF-kappaB transcription factors can be triggered by a host of stress-related stimuli including pro-inflammatory cytokines, excessive mechanical stress and ECM degradation products. Activated NF-kappaB regulates the expression of many cytokines and chemokines, adhesion molecules, inflammatory mediators, and several matrix degrading enzymes. NF-kappaB also influences the regulated accumulation and remodeling of ECM proteins and has indirect positive effects on downstream regulators of terminal chondrocyte differentiation (including beta-catenin and Runx2). Although driven partly by pro-inflammatory and stress-related factors, OA pathogenesis also involves a "loss of maturational arrest" that inappropriately pushes chondrocytes towards a more differentiated, hypertrophic-like state. Growing evidence points to NF-kappaB signaling as not only playing a central role in the pro-inflammatory stress-related responses of chondrocytes to extra- and intra-cellular insults, but also in the control of their differentiation program. Thus unlike other signaling pathways the NF-kappaB activating kinases are potential therapeutic OA targets for multiple reasons. Targeted strategies to prevent unwanted NF-kappaB activation in this context, which do not cause side effects on other proteins or signaling pathways, need to be focused on the use of highly specific drug modalities, siRNAs or other biological inhibitors that are targeted to the activating NF-kappaB kinases IKKalpha or IKKbeta or specific activating canonical NF-kappaB subunits. However, work remains in its infancy to evaluate the effects of efficacious, targeted NF-kappaB inhibitors in animal models of OA disease in vivo and to also target these strategies only to affected cartilage and joints to avoid other undesirable systemic effects.