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RSA 2003 Abstracts
University of Colorado Health Sciences Center
A KNOWLEDGE BASE FOR AUTOMATED INFERENCING AND HYPOTHESIS GENERATION
Acquaah-Mensah, George K.; McGoldrick, Daniel J.; Eberlein, Jens; Ogren Phillip, V.; Gabow, Aaron; Hunter, LawrenceCenter for Computational Pharmacology, Department of Pharmacology, The University of Colorado School of Medicine, Denver, Colorado 80262
Knowledge bases constitute a fundamental component of artificial intelligence systems. This report introduces Biognosticopoeia, a frame-based object-oriented knowledge representation that has key aspects of the pharmacology of alcoholism as a principal focus. Knowledge concepts, obtained from the biomedical literature, were represented using four primary conceptual object hierarchies: ligands, proteins, processes and anatomy. The ligands hierarchy includes such attributes as chemical classification, target receptor, synthesis mechanism, activation and inactivation mechanisms, and anatomical distribution of instances. The proteins hierarchy has such attributes as subunits and components, structural features, active forms, anatomical distribution and physiological effects. The process hierarchy presents a breakdown of process types, and includes the component actions that constitute key physiological and behavioral processes. These hierarchies work together by way of concepts that are linked by attributes consisting of concepts from other hierarchies. To facilitate the process of updating the knowledge base, a graphical user interface, Knedit, has been designed and implemented. A validation system set up to monitor the the growth, machine-readability, and richness of the knowledge representation indicates, among others, that the knowledge base grew from 1213 concepts and 3537 concept attribute values in July 2002 to 3783 concepts and 10301 concept attribute values in December 2002. These concepts and attributes provide the essential groundwork for generating inferences concerning physiological, behavioral and pharmacological events. Such automated inferencing could provide a gateway for hypothesis generation and knowledge discovery.
INNATE DIFFERENCES IN PROTEIN EXPRESSION IN THE NUCLEUS ACCUMBENS AND HIPPOCAMPUS OF INBRED ALCOHOL-PREFERRING (IP) AND -NONPREFERRING (INP) RATS
Frank A. Witzmann, Junyu Li, Wendy N. Strother, William J. McBride, Lawrence Hunter, David W. Crabb, Lawrence Lumeng, Ting-Kai Li
Departments of Cell & Integrative Physiology, Medicine and Psychiatry, Institute for Psychiatric Research, Indiana Univ Sch Med, Indianapolis, IN 46202; Depart Pharmacol, University of Colorado Health Sciences Center, Denver, CO
Two-dimensional gel electrophoresis (2-DE) was used to separate protein samples solubilized from the nucleus accumbens and hippocampus of alcohol-naïve, adult, male inbred alcohol-preferring (iP) and alcohol-non-preferring (iNP) rats (n = 5 each strain). Several protein spots were excised from the gel, de-stained, digested with typsin, and analyzed by mass spectrometry. In the hippocampus, the abundances of 8 proteins (only 2 of which were identified) were higher in the iNP than iP rat. In the nucleus accumbens, the abundances of 31 of 32 proteins (of which 21 were identified) were higher in the iNP than iP rat. Higher abundances of cellular retinoic acid-binding protein 1 and a calmodulin-dependent protein kinase (both of which are involved in cellular signaling pathways) were found in both regions of the iNP than iP rat. In the nucleus accumbens, additional differences in the abundances of proteins involved in (a) metabolism (e.g.,calpain, parkin, glucokinase, apolipoprotein E, sorbitol dehydrogenase), (b) cyto-skeletal and intracellular protein transport (e.g., beta actin), (c) molecular chaperoning (e.g., grp 78, hsc70, hsc 60, grp75, prohibitin), (d) cellular signaling pathways (e.g., protein kinase C-binding protein), (e) synaptic function (e.g., complexin I, gamma enolase, syndapin IIbb), (f) reduction of oxidative stress (thioredoxin peroxidase), and (g) growth and differentiation (hippocampal cholinergic neurostimulating peptide) were found. The results of this study indicate that selective breeding for disparate alcohol drinking behaviors produced innate alterations in the expression of several proteins that could influence neuronal function within the nucleus accumbens and hippocampus. (Supported by AA07611, AA13521 [INIA], AA13524 [INIA] and the Indiana Genomics Initiative).
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