@article{kakaley_wang_leblanc_2017, title={Agonist-mediated assembly of the crustacean methyl farnesoate receptor}, volume={7}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/srep45071}, DOI={10.1038/srep45071}, abstractNote={AbstractThe methyl farnesoate receptor (MfR) orchestrates aspects of reproduction and development such as male sex determination in branchiopod crustaceans. Phenotypic endpoints regulated by the receptor have been well-documented, but molecular interactions involved in receptor activation remain elusive. We hypothesized that the MfR subunits, methoprene-tolerant transcription factor (Met) and steroid receptor coactivator (SRC), would be expressed coincident with the timing of sex programming of developing oocytes by methyl farnesoate in daphnids. We also hypothesized that methyl farnesoate activates MfR assembly. Met mRNA was expressed rhythmically during the reproductive cycle, with peak mRNA accumulation just prior period of oocytes programming of sex. Further, we revealed evidence that Met proteins self-associate in the absence of methyl farnesoate, and that the presence of methyl farnesoate stimulates dissociation of Met multimers with subsequent association with SRC. Results demonstrated that the Met subunit is highly dynamic in controlling the action of methyl farnesoate through temporal variation in its expression and availability for receptor assembly.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Kakaley, Elizabeth K. Medlock and Wang, Helen Y. and LeBlanc, Gerald A.}, year={2017}, month={Mar} }
 @article{gorr_rider_wang_olmstead_leblanc_2006, title={A candidate juvenoid hormone receptor cis-element in the Daphnia magna hb2 hemoglobin gene promoter}, volume={247}, ISSN={["0303-7207"]}, DOI={10.1016/j.mce.2005.11.022}, abstractNote={Hemoglobin levels are significantly elevated in the crustacean Daphnia magna by juvenoid hormones. The present study was undertaken to identify the specific globin (hb) genes that are induced by juvenoids and to identify putative juvenoid response elements (JREs) that may mediate this induction. Gene product of globin 2 (hb2), but not globin 1 and globin 3, was robustly elevated following juvenoid treatment of daphnids. A candidate JRE, located in the promoter of hb2, bound activated factor(s) in response to juvenoid treatment of daphnids. This hormone-induced protein:JRE interaction was robust when daphnids were reared at high oxygen tension but was inhibited when daphnids were reared under low pO2, implying that hypoxia might act to disrupt juvenoid-mediated endocrine signaling. The candidate JRE consists of a steroid/retinoid-response element-like core adjacent to a 5' AT-rich extension and thus bears resemblance to response elements that bind monomeric nuclear receptors. The induction of hb2 mRNA levels by juvenoid treatment occurred rapidly (within 4 h of exposure) and was not attenuated by treatment of daphnids with cycloheximide. In contrast, cycloheximide treatment did block hormone-mediated elevations in hemoglobin protein levels. Thus, induction of hb2 by juvenoids was not dependent upon the synthesis of secondary transcription factors that bound the JRE but was likely due to activation of the gene directly by the juvenoid-receptor complex. Affinity pull-down experiments with nuclear proteins extracted from juvenoid-treated daphnids using the JRE as bait yielded a 52kDa candidate for a monomeric nuclear receptor in D. magna that may mediate the regulatory activity of juvenoids.}, number={1-2}, journal={MOLECULAR AND CELLULAR ENDOCRINOLOGY}, author={Gorr, TA and Rider, CV and Wang, HY and Olmstead, AW and LeBlanc, GA}, year={2006}, month={Mar}, pages={91–102} }
 @article{wang_olmstead_li_leblanc_2005, title={The screening of chemicals for juvenoid-related endocrine activity using the water flea Daphnia magna}, volume={74}, ISSN={["1879-1514"]}, DOI={10.1016/j.aquatox.2005.05.010}, abstractNote={U.S. Environmental Protection Agency is charged with developing a screening and testing paradigm for detecting endocrine toxicity of chemicals that are subject to regulation under the Food Quality Protection and the Safe Drinking Water Acts. In this study, we developed and evaluated a screening assay that could be employed to detect juvenoid-related endocrine-modulating activity in an invertebrate species. Juvenoid activity, anti-juvenoid activity, and juvenoid potentiator activity of chemicals was assessed using the water flea Daphnia magna. Male sex determination is under the regulatory control of juvenoid hormone, presumably methyl farnesoate, and this endpoint was used to detect juvenoid modulating activity of chemicals. Eighteen chemicals were evaluated for juvenoid agonist activity. Positive responses were detected with the juvenoid hormones methyl farnesoate and juvenile hormone III along with the insect growth regulating insecticides pyriproxyfen, fenoxycarb, and methoprene. Weak juvenoid activity also was detected with the cyclodiene insecticide dieldrin. Assays performed repetitively with compounds that gave either strong positive, weak positive, or negative response were 100% consistent indicating that the assay is not prone to false positive or negative responses. Five candidate chemicals were evaluated for anti-juvenoid activity and none registered positive. Four chemicals (all trans-retinoic acid, methoprene, kinoprene, bisphenol A) also were evaluated for their ability to potentiate the activity of methyl farnesoate. All registered positive. Results demonstrate that an in vivo assay with a crustacean species customarily employed in toxicity testing can be used to effectively screen chemicals for juvenoid-modulating activity.}, number={3}, journal={AQUATIC TOXICOLOGY}, author={Wang, HY and Olmstead, AW and Li, H and LeBlanc, GA}, year={2005}, month={Sep}, pages={193–204} }