Nucleotide-regulated calcium signaling in lung fibroblasts and epithelial cells from normal and P2Y2 receptor (-/-) mice

To test for the role of the P2Y2 receptor(P2Y2-R) in the regulation of nucleotide-promoted Ca2+ signaling in the lung, we generated P2Y2-R- deficient (P2Y2-R(-/-)) mice and measured intracellular Ca2+(i) responses (ΔCa2+(i)) to nucleotides in cultured lung fibroblasts and nasal and tracheal epithelial cells from wild type and P2Y2-R(-/-) mice. In the wild type fibroblasts, the rank order of potencies for nucleotide-induced ΔCa2+(i) was as follows: UTP ≥ ATP >> ADP > UDP. The responses induced by these agonists were completely absent in the P2Y2R(-/-) fibroblasts. Inositol phosphate responses paralleled those of ACa2+(i) in both groups. ATP and UTP also induced Ca2+(i) responses in wild type airway epithelial cells. In the P2Y2-R(-/-) airway epithelial cells, UTP was ineffective. A small fraction (25%) of the ATP response persisted. Adenosine and α,β- methylene ATP were ineffective, and ATP responses were not affected by adenosine deaminase or by removal of extracellular Ca2+, indicating that neither P1 nor P2X receptors mediated this residual ATP response. In contrast, 2-methylthio-ADP promoted a substantial Ca2+(i) response in P2Y2-R(-/-) cells, which was inhibited by the P2Y1 receptor antagonist adenosine 3'-5'-diphosphate. These studies demonstrate that P2Y2-R is the dominant purinoceptor in airway epithelial cells, which also express a P2Y1 receptor, and that the P2Y2-R is the sole purinergic receptor subtype mediating nucleotide-induced inositol lipid hydrolysis and Ca2+ mobilization in mouse lung fibroblasts

Regulation of the androgen receptor by SET9-mediated methylation

The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain communication between the N- and C-termini and recruitment to androgen-target genes. We also show that SET9 is pro-proliferative and anti-apoptotic in prostate cancer cells and demonstrates up-regulated nuclear expression in prostate cancer tissue. In all, our date indicate a new mechanism of AR regulation that may be therapeutically exploitable for prostate cancer treatment

Using behavior-analytic implicit tests to assess sexual interests among normal and sex-offender populations

The development of implicit tests for measuring biases and behavioral predispositions is a recent development within psychology. While such tests are usually researched within a social-cognitive paradigm, behavioral researchers have also begun to view these tests as potential tests of conditioning histories, including in the sexual domain. The objective of this paper is to illustrate the utility of a behavioral approach to implicit testing and means by which implicit tests can be built to the standards of behavioral psychologists. Research findings illustrating the short history of implicit testing within the experimental analysis of behavior are reviewed. Relevant parallel and overlapping research findings from the field of social cognition and on the Implicit Association Test are also outlined. New preliminary data obtained with both normal and sex offender populations are described in order to illustrate how behavior-analytically conceived implicit tests may have potential as investigative tools for assessing histories of sexual arousal conditioning and derived stimulus associations. It is concluded that popular implicit tests are likely sensitive to conditioned and derived stimulus associations in the history of the test-taker rather than 'unconscious cognitions', per se

Anxiety as a cause of attachment avoidance in women with Turner Syndrome

Working models of attachment are internal depictions of self relative to others and have been described in terms of two dimensions: (1) attachment avoidance and (2) attachment anxiety. An exploratory qualitative study was carried out to build understandings about women with Turner Syndrome (TS) and the psychosocial impact their infertility has upon salient relationships. In one-to-one semi-structured interviews, five women with TS were asked: How do you perceive your womanhood and infertility status has affected your relationships with: (1) the opposite sex, (2) siblings and (3) peers? In opposite-sex relationships, infertility status was found to arouse fear of ending up alone and anxiety over engaging in romantic relationships. In sibling relationships, jealousy was expressed in relation to disparity with sister(s) more natural maturation to womanhood, and, within peer relationships, consequences from divulging infertility status created attachment avoidance with friends. Further investigation in this area is merited