The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by tbx5 deficiency in zebrafish (Danio rerio) embryos.

BACKGROUND: Dysmorphogenesis and multiple organ defects are well known in zebrafish (Danio rerio) embryos with T-box transcription factor 5 (tbx5) deficiencies, mimicking human Holt-Oram syndrome. METHODS: Using an oligonucleotide-based microarray analysis to study the expression of special genes in tbx5 morphants, we demonstrated that GH and some GH-related genes were markedly downregulated. Zebrafish embryos microinjected with tbx5-morpholino (MO) antisense RNA and mismatched antisense RNA in the 1-cell stage served as controls, while zebrafish embryos co-injected with exogenous growth hormone (GH) concomitant with tbx5-MO comprised the treatment group. RESULTS: The attenuating effects of GH in tbx5-MO knockdown embryos were quantified and observed at 24, 30, 48, 72, and 96 h post-fertilization. Though the understanding of mechanisms involving GH in the tbx5 functioning complex is limited, exogenous GH supplied to tbx5 knockdown zebrafish embryos is able to enhance the expression of downstream mediators in the GH and insulin-like growth factor (IGF)-1 pathway, including igf1, ghra, and ghrb, and signal transductors (erk1, akt2), and eventually to correct dysmorphogenesis in various organs including the heart and pectoral fins. Supplementary GH also reduced apoptosis as determined by a TUNEL assay and decreased the expression of apoptosis-related genes and proteins (bcl2 and bad) according to semiquantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis, respectively, as well as improving cell cycle-related genes (p27 and cdk2) and cardiomyogenetic genes (amhc, vmhc, and cmlc2). CONCLUSIONS: Based on our results, tbx5 knockdown causes a pseudo GH deficiency in zebrafish during early embryonic stages, and supplementation of exogenous GH can partially restore dysmorphogenesis, apoptosis, cell growth inhibition, and abnormal cardiomyogenesis in tbx5 knockdown zebrafish in a paracrine manner.

Involving consumers in product design through collaboration: the case of online role-playing games.

The release of software attributes to users by software designers for the creation of user-designed forms is regarded as a producer-consumer collaboration, leading consumers to expend significant effort on a specific product. This article identifies such software/product attributes within online role-playing games and then explores how consumers' prior experience affects the evaluation of such attributes. In this article, product attributes comprise customized, content, and interactive externality-sensitive and complementary externality-sensitive attributes, with the value of each attribute being greater for experts than for novices. In Study 1, data were collected and analyzed for the purpose of identifying such features in online role-playing games. The results can also be generalized to convergent products, such as TV games that have been redesigned as online games or mobile games found in Study 2. For the introduction of a convergent product to be successful, our research suggests that the potential market-segment focus should be on knowledgeable consumers who accept such products more readily.