FGF21 mediates corticosteroidrelated bone mass loss through PPAR gamma Hormones such as fibroblast growth factor 21 (FGF21) and glucocorticoids (GCs) play crucial roles in bone metabolism. Longterm treatment with corticosteroid drugs may lead to glucocorticoidrelated osteoporosis, and previous studies have defined FGF21 as a factor may participate in bone metabolism and most studies showed that it negatively regulates bone metabolism. Herein we examine the interplay between these factors in bone metabolism. In our study, expressions of PPAR, ALP, and TRAP5b were compared between WT mice and FGF21 inhibited mice (FGFi mice) and WT and FGFi mice treated with adrenocorticotropic hormone (ACTH). We found ACTH treatment significantly blocked ALP decreases in FGFi mice as compared to WT whereas TRAP5b expression was significantly increased ( p  ). Collectively, our findings suggest the following: FGF21 may serve as a negative regulator of bone metabolism, the negative regulation of bone metabolism via FGF21 may require the  textPPARgamma  pathway, and FGF21 may be involved in the ACTHCortisol axisrelated bone mass loss.

Testing multiple hypotheses through IMP weighted FDR based on a genetic functional network with application to a new zebrafish transcriptome study In genomewide studies, hundreds of thousands of hypothesis tests are performed simultaneously. Bonferroni correction and False Discovery Rate (FDR) can effectively control type I error but often yield a high false negative rate. We aim to develop a more powerful method to detect differentially expressed genes. We present a Weighted False Discovery Rate (WFDR) method that incorporate biological knowledge from genetic networks. We first identify weights using Integrative Multispecies Prediction (IMP) and then apply the weights in WFDR to identify differentially expressed genes through an IMPWFDR algorithm. We performed a gene expression experiment to identify zebrafish genes that change expression in the presence of arsenic during a systemic Pseudomonas aeruginosa infection. Zebrafish were exposed to arsenic at 10 parts per billion andor infected with P. aeruginosa. Appropriate controls were included. We then applied IMPWFDR during the analysis of differentially expressed genes. We compared the mRNA expression for each group and found over 200 differentially expressed genes and several enriched pathways including defense response pathways, arsenic response pathways, and the Notch signaling pathway.