ABSTRACT
Background: Crohn's Disease (CD) is an inflammatory disease of the gastrointestinal tract that affects millions of patients. While great strides have been made in treatment, namely in biologic therapy such as anti-TNF drugs, CD remains a significant health burden. Method: We conducted two meta-analyses using our STARGEO platform to tag samples from Gene Expression Omnibus. One analysis compares inactive colonic biopsies from CD patients to colonic biopsies from healthy patients as a control and the other compares colonic biopsies from active CD lesions to inactive lesions. Separate tags were created to tag colonic samples from inflamed biopsies (total of 65 samples) and quiescent tissue in CD patients (total of 39 samples), and healthy tissue from non-CD patients (total of 30 samples). Results from the two meta-analyses were analyzed using Ingenuity Pathway Analysis. Results: For the inactive CD vs healthy tissue analysis, we noted FXR/RXR and LXR/RXR activation, superpathway of citrulline metabolism, and atherosclerosis signaling as top canonical pathways. The top upstream regulators include genes implicated in innate immunity, such as TLR3 and HNRNPA2B1, and sterol regulation through SREBF2. In addition, the sterol regulator SREBF2, lipid metabolism was the top disease network identified in IPA (Fig. 1). Top upregulated genes hold implications in innate immunity (DUOX2, REG1A/1B/3A) and cellular transport and absorption (ABCG5, NPC1L1, FOLH1, and SLC6A14). Top downregulated genes largely held roles in cell adhesion and integrity, including claudin 8, PAQR5, and PRKACB.For the active vs inactive CD analysis, we found immune cell adhesion and diapedesis, hepatic fibrosis/hepatic stellate cell activation, LPS/IL-1 inhibition of RXR function, and atherosclerosis as top canonical pathways. Top upstream regulators included inflammatory mediators LPS, TNF, IL1B, and TGFB1. Top upregulated genes function in the immune response such as IL6, CXCL1, CXCR2, MMP1/7/12, and PTGS2. Downregulated genes dealt with cellular metabolism and transport such as CPO, RBP2, G6PC, PCK1, GSTA1, and MEP1B. Conclusion: Our results build off established and recently described research in the field of CD. We demonstrate the use of our user-friendly platform, STARGEO, in investigating disease and finding therapeutic avenues.
ABSTRACT
Male courtship vocalizations represent a potent signal designed to attract females; however, not all females find male signals equally attractive. We explored the possibility that the affective state induced by hearing courtship vocalizations depends on the motivational state of a receiver. We used a conditioned place preference test of reward to determine the extent to which the rewarding properties of hearing male courtship song differed in female European starlings categorized as nest box owners (a sign of breeding readiness) or non-owners. Nest box owners developed a preference for a chamber in which they previously heard male courtship song. Non-owners displayed no preference for a chamber in which they previously heard song. Positive correlations were identified between the preference a female developed for the song-paired chamber and female nesting and dominance behaviors observed prior to conditioning (indices of the motivation to breed). Immunolabeling for met-enkephalin (an opioid neuropeptide involved in reward) in the medial preoptic nucleus, ventromedial nucleus of the hypothalamus, nucleus accumbens, and periaqueductal gray was higher in females with compared to those without nest boxes. Both nest box entries and song-induced place preference also correlated positively with met-enkephalin labeling in the ventromedial nucleus of the hypothalamus. These findings indicate that the reward value of vocal signals is linked to individual differences in motivational state; and that differences in enkephalin activity may play a role in modifying an individual's motivational state and/or the reward value of song.
