Canonical wnt signaling activity in early stages of chick lung development

Wnt signaling pathway is an essential player during vertebrate embryonic development which has been associated with several developmental processes such as gastrulation, body axis formation and morphogenesis of numerous organs, namely the lung. Wnt proteins act through specific transmembrane receptors, which activate intracellular pathways that regulate cellular processes such as cell proliferation, differentiation and death. Morphogenesis of the fetal lung depends on epithelial-mesenchymal interactions that are governed by several growth and transcription factors that regulate cell proliferation, fate, migration and differentiation. This process is controlled by different signaling pathways such as FGF, Shh and Wnt among others. Wnt signaling is recognized as a key molecular player in mammalian pulmonary development but little is known about its function in avian lung development. The present work characterizes, for the first time, the expression pattern of several Wnt signaling members, such as wnt-1, wnt-2b, wnt-3a, wnt-5a, wnt-7b, wnt-8b, wnt-9a, lrp5, lrp6, sfrp1, dkk1, β-catenin and axin2 at early stages of chick lung development. In general, their expression is similar to their mammalian counterparts. By assessing protein expression levels of active/total β-catenin and phospho-LRP6/LRP6 it is revealed that canonical Wnt signaling is active in this embryonic tissue. In vitro inhibition studies were performed in order to evaluate the function of Wnt signaling pathway in lung branching. Lung explants treated with canonical Wnt signaling inhibitors (FH535 and PK115-584) presented an impairment of secondary branch formation after 48 h of culture along with a decrease in axin2 expression levels. Branching analysis confirmed this inhibition. Wnt-FGF crosstalk assessment revealed that this interaction is preserved in the chick lung. This study demonstrates that Wnt signaling is crucial for precise chick lung branching and further supports the avian lung as a good model for branching studies since it recapitulates early mammalian pulmonary development.Rute S. Moura was supported by a grant of ON.2 SR&TD Integrated Program (N-01-01-0124-01-07), ref: UMINHO/BPD/31/2013. The funders had no role in study design, data collection and analysis

Psychosis in bipolar disorder: Phenomenology and impact on morbidity and course of illness

Although psychosis is common in bipolar disorder, few studies have examined the prognostic significance of psychotic features. In addition, some studies suggest that the presence of mood-incongruent psychosis, in particular, is associated with poorer outcome compared with mood-congruent psychosis. We assesses the phenomenology and prevalence of mood-congruent and mood-incongruent psychotic symptoms in 352 patients with bipolar I disorder participating in the Stanley Foundation Bipolar Treatment Network. We compared the demographic and clinical features, and measures of psychosocial and vocational functioning in patients with and without a history of psychosis. The phenomenology of psychosis in this cohort of patients with bipolar disorder was similar to that reported in earlier studies and supported the lack of diagnostic specificity of any one type of psychotic symptom. There were no significant differences between patients with and without a history of psychosis on any demographic, psychosocial, vocational, or course of illness variables. Only family history of bipolar disorder was significantly more common in patients with nonpsychotic bipolar disorder compared to patients with a history of psychosis. Among bipolar patients with a history of psychosis, only the proportion of women and lifetime prevalence rates of anxiety disorders occurred significantly more in patients with mood-incongruent delusions. In this large cohort of outpatients with bipolar I disorder, neither a history of psychosis nor of mood-incongruent psychosis had prognostic significance at entry into the Network. The lack of observable prognostic impact may have been, in part, due to the relatively high morbidity and poor functional outcome of a substantial portion of the total cohort. (C) 2003 Elsevier Inc. All rights reserved