Novel potential interacting partners of fibronectin in spontaneous animal model of interstitial cystitis

Feline idiopathic cystitis (FIC) is the only spontaneous animal model for human interstitial cystitis (IC), as both possess a distinctive chronical and relapsing character. Underlying pathomechanisms of both diseases are not clearly established yet. We recently detected increased urine fibronectin levels in FIC cases. The purpose of this study was to gain further insight into the pathogenesis by assessing interacting partners of fibronectin in urine of FIC affected cats. Several candidate proteins were identified via immunoprecipitation and mass spectrometry. Considerable changes in FIC conditions compared to physiological expression of co-purified proteins were detected by Western blot and immunohistochemistry. Compared to controls, complement C4a and thioredoxin were present in higher levels in urine of FIC patients whereas loss of signal intensity was detected in FIC affected tissue. Galectin-7 was exclusively detected in urine of FIC cats, pointing to an important role of this molecule in FIC pathogenesis. Moderate physiological signal intensity of galectin-7 in transitional epithelium shifted to distinct expression in transitional epithelium under pathophysiological conditions. I-FABP expression was reduced in urine and urinary bladder tissue of FIC cats. Additionally, transduction molecules of thioredoxin, NF-κB p65 and p38 MAPK, were examined. In FIC affected tissue, colocalization of thioredoxin and NF-κB p65 could be demonstrated compared to absent coexpression of thioredoxin and p38 MAPK. These considerable changes in expression level and pattern point to an important role for co-purified proteins of fibronectin and thioredoxin-regulated signal transduction pathways in FIC pathogenesis. These results could provide a promising starting point for novel therapeutic approaches in the future

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Ralph Bergold / Helga Gisbertz / Gerhard Kruip (Hrsg.): Treffpunkt Ethik. Internetbasierte Lernumgebungen für ethische Diskurse. Bielefeld: Bertelsmann 2007 (508 S.) [Rezension]

Rezension von: Ralph Bergold / Helga Gisbertz / Gerhard Kruip (Hrsg.): Treffpunkt Ethik. Internetbasierte Lernumgebungen für ethische Diskurse. Bielefeld: Bertelsmann 2007 (508 S.; ISBN 978-3-7639-3538-3; 36,90 EUR)

Rolf Arnold: Die emotionale Konstruktion der Wirklichkeit. Beiträge zu einer emotionspädagogischen Erwachsenenbildung. Baltmannsweiler: Schneider 2005 (282 S.) [Rezension]

Rezension von: Rolf Arnold: Die emotionale Konstruktion der Wirklichkeit. Beiträge zu einer emotionspädagogischen Erwachsenenbildung. Baltmannsweiler: Schneider 2005 (282 S.; ISBN 3-89676-921-9; 20,00 EUR)

Martin Dust: "Unser Ja zum neuen Deutschland". Katholische Erwachsenenbildung von der Weimarer Republik zur Nazi-Diktatur (Studien zur Bildungsreform; Bd. 49). Frankfurt am Main: Lang 2007 (631 S.) [Rezension]

Rezension von: Martin Dust: "Unser Ja zum neuen Deutschland". Katholische Erwachsenenbildung von der Weimarer Republik zur Nazi-Diktatur (Studien zur Bildungsreform; Bd. 49). Frankfurt am Main: Lang 2007 (631 S.; ISBN 978-3-631-55693-1; 97,50 EUR)

Roswitha Peters: Erwachsenenbildungs-Professionalität. Ansprüche und Realitäten. Bielefeld: W. Bertelsmann Verlag 2004 (240 S.) [Rezension]

Rezension von: Roswitha Peters: Erwachsenenbildungs-Professionalität. Ansprüche und Realitäten. Bielefeld: W. Bertelsmann Verlag 2004 (240 S.; ISBN 3-7639-1898-1; 22,90 EUR)

Expression of co-purified proteins in healthy bladder tissue.

<p>Immunohistochemical double labelling of CD117 and co-purified proteins in a representative healthy bladder tissue. DIC image of healthy bladder tissue (A). CD117 (green) shows a marked reactivity in the epithelial cells of the urothel and in the interstitial cells of the lamina propria of the healthy bladder (B). Overlay image of C4a (red) and CD117 (green) reveals considerable co-localization (overlapping results in yellow colour) at the cell nuclei of the urothelial cells and a scattered expression in the interstitial cells of the lamina propria (C). Galectin-7 (red) and CD117 (green) show a co-localization in the umbrella cells (marked with an asterisk) of the transitional cell epithelium, whereas reactivity of both proteins in the epithelial cells of the urothel indicate a co-expression. Cells of the lamina propria are only CD117 positive (D). I-FABP (red) and CD117 (green) overlay is visible only in the interstitial cells of the lamina propria. Additionally, I-FABP reactivity is seen extracellularly and is distinctly expressed in the basal membrane (E). Thioredoxin (red) and CD117 (green) co-localize distinctly at all cell nuclei of the transitional epithelial cells and in the interstitial cells of the subepithelial tunic (F). The blue colour reveals staining of cell nuclei (DAPI). a = Transitional cell epithelium, b = Lamina propria mucosae, c = Inserted box shows magnification of respective cells in the lamina propria mucosae.</p