The 2 structurally and functionally related peptides, neuropeptide B (NPB) and neuropeptide W (NPW), together with their receptor(s) (NPBWR1/NPBWR2) constitute the NPB/NPW system, which acts mainly on the central nervous system to regulate many physiological processes in mammals. However, little is known about this NPB/NPW system in nonmammalian vertebrates. In this study, the functionality and expression of this NPB/NPW system and its actions on the pituitary were investigated in chickens. The results showed that: 1) chicken NPB/NPW system comprises an NPB peptide of 28 amino acids (cNPB28), an NPW peptide of 23 or 30 amino acids (cNPW23/cNPW30), and their 2 receptors (cNPBWR1 and cNPBWR2), which are highly homologous to their human counterparts. 2) Using a pGL3-CRE-luciferase reporter system, we demonstrated that cNPBWR2 expressed in Chinese hamster ovary cells can be potently activated by cNPW23 (not cNPB28), and its activation inhibits the intracellular cAMP signaling pathway, whereas cNPBWR1 shows no response to peptide treatment, suggesting a crucial role of cNPBWR2 in mediating cNPW/cNPB actions. 3) Quantitative real-time PCR revealed that cNPW and cNPB are widely expressed in chicken tissues, including hypothalamus, whereas cNPBWR1 and cNPBWR2 are mainly expressed in brain or pituitary. 4) In accordance with abundant cNPBWR2 expression in pituitary, cNPW23 could dose dependently inhibit GH and prolactin secretion induced by GHRH and vasoactive intestinal polypeptide, respectively, in cultured chick pituitary cells, as monitored by Western blotting. Collectively, our data reveal a functional NPB/NPW system in birds and offer the first proof that NPW can act directly on pituitary to inhibit GH/prolactin secretion in vertebrates.
A partial duplication of the prolactin (PRL) receptor gene (designated as dPRLR) has been identified at the late-feathering (LF) K locus on chromosome Z of some chicken strains recently, implying that dPRLR is probably a candidate gene associated with LF development in chickens. However, little is known about the structure, functionality, and spatiotemporal expression of the dPRLR gene in chickens. In this study, using 3 0 -RACE and RT-PCR, the full-length cDNA of the dPRLR obtained from the kidneys of male Lohmann layer chickens carrying a K allele was cloned. The cloned dPRLR is predicted to encode a membranespanning receptor of 683 amino acids, which is nearly identical to the original PRLR, except for its lack of a 149-amino acid C-terminal tail. Using a 5! STAT5-Luciferase reporter system and western blot analysis, we demonstrated that dPRLR expressed in HepG2 cells could be potently activated by chicken PRL and functionally coupled to the intracellular STAT5 signaling pathway, suggesting that dPRLR may function as a novel receptor for PRL. RT-PCR assays revealed that similar to the original PRLR gene, dPRLR mRNA is widely expressed in all embryonic and adult tissues examined including the skin of male Lohmann chickens with a K allele. These findings, together with the expression of PRL mRNA detected in the skin of embryos at embryonic day 20 and 1-week-old chicks, suggest that skin-expressed dPRLR and PRLR, together with plasma and skin-derived PRL, may be involved in the control of the LF development of chicks at hatching. Moreover, the wide tissue expression of dPRLR implies that dPRLR may regulate other physiological processes of chickens carrying the K allele.
ObjectiveOur study aimed to systematically review the methodological characteristics of studies that identified prognostic factors or developed or validated models for predicting mortalities among patients with acute aortic dissection (AAD), which would inform future work.Design/settingA methodological review of published studies.MethodsWe searched PubMed and EMBASE from inception to June 2020 for studies about prognostic factors or prediction models on mortality among patients with AAD. Two reviewers independently collected the information about methodological characteristics. We also documented the information about the performance of the prognostic factors or prediction models.ResultsThirty-two studies were included, of which 18 evaluated the performance of prognostic factors, and 14 developed or validated prediction models. Of the 32 studies, 23 (72%) were single-centre studies, 22 (69%) used data from electronic medical records, 19 (59%) chose retrospective cohort study design, 26 (81%) did not report missing predictor data and 5 (16%) that reported missing predictor data used complete-case analysis. Among the 14 prediction model studies, only 3 (21%) had the event per variable over 20, and only 5 (36%) reported both discrimination and calibration statistics. Among model development studies, 3 (27%) did not report statistical methods, 3 (27%) exclusively used statistical significance threshold for selecting predictors and 7 (64%) did not report the methods for handling continuous predictors. Most prediction models were considered at high risk of bias. The performance of prognostic factors showed varying discrimination (AUC 0.58 to 0.95), and the performance of prediction models also varied substantially (AUC 0.49 to 0.91). Only six studies reported calibration statistic.ConclusionsThe methods used for prognostic studies on mortality among patients with AAD—including prediction models or prognostic factor studies—were suboptimal, and the model performance highly varied. Substantial efforts are warranted to improve the use of the methods in this population.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.