@article{hannas_wang_thomson_kwon_li_leblanc_2011, title={Regulation and dysregulation of vitellogenin mRNA accumulation in daphnids (Daphnia magna)}, volume={101}, ISSN={["1879-1514"]}, DOI={10.1016/j.aquatox.2010.11.006}, abstractNote={The induction of vitellogenin in oviparous vertebrates has become the gold standard biomarker of exposure to estrogenic chemicals in the environment. This biomarker of estrogen exposure also has been used in arthropods, however, little is known of the factors that regulate the expression of vitellogenin in these organisms. We investigated changes in accumulation of mRNA products of the vitellogenin gene Vtg2 in daphnids (Daphnia magna) exposed to a diverse array of chemicals. We further evaluated the involvement of hormonal factors in the regulation of vitellogenin expression that may be targets of xenobiotic chemicals. Expression of the Vtg2 gene was highly responsive to exposure to various chemicals with an expression range spanning approximately four orders of magnitude. Chemicals causing the greatest induction were piperonyl butoxide, chlordane, 4-nonylphenol, cadmium, and chloroform. Among these, only 4-nonylphenol is recognized to be estrogenic. Exposure to several chemicals also suppressed Vtg2 mRNA levels, as much as 100-fold. Suppressive chemicals included cyproterone acetate, acetone, triclosan, and atrazine. Exposure to the estrogens diethylstilbestrol and bisphenol A had little effect on vitellogenin mRNA levels further substantiating that these genes are not induced by estrogen exposure. Exposure to the potent ecdysteroids 20-hydroxyecdysone and ponasterone A revealed that Vtg2 was subject to strong suppressive control by these hormones. Vtg2 mRNA levels were not significantly affected from exposure to several juvenoid hormones. Results indicate that ecdysteroids are suppressors of vitellogenin gene expression and that vitellogenin mRNA levels can be elevated or suppressed in daphnids by xenobiotics that elicit antiecdysteroidal or ecdysteroidal activity, respectively. Importantly, daphnid Vtg2 is not elevated in response to estrogenic activity.}, number={2}, journal={AQUATIC TOXICOLOGY}, author={Hannas, Bethany R. and Wang, Ying H. and Thomson, Susanne and Kwon, Gwijun and Li, Hong and LeBlanc, Gerald A.}, year={2011}, month={Jan}, pages={351–357} }
 @article{wang_kwon_li_leblanc_2011, title={Tributyltin Synergizes with 20-Hydroxyecdysone to Produce Endocrine Toxicity}, volume={123}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfr154}, abstractNote={One of the great challenges facing modern toxicology is in predicting the hazard associated with chemical mixtures. The development of effective means of predicting the toxicity of chemical mixtures requires an understanding of how chemicals interact to produce nonadditive outcomes (e.g., synergy). We hypothesized that tributyltin would elicit toxicity in daphnids (Daphnia magna) by exaggerating physiological responses to 20-hydroxyecdysone signaling via synergistic activation of the retinoid X receptor (RXR):ecdysteroid receptor (EcR) complex. Using reporter gene assays, we demonstrated that RXR, alone, is activated by a variety of ligands including tributyltin, whereas RXR:EcR heterodimers were not activated by tributyltin. However, tributyltin, in combination with the daphnid EcR ligand 20-hydroxyecdysone, caused concentration-dependent, synergistic activation of the RXR:EcR reporter. Electrophoretic mobility shift assays revealed that tributyltin did not enhance the activity of 20-hydroxyecdysone by increasing binding of the receptor complex to a DR-4 DNA-binding site. Exposure of daphnids to elevated concentrations of 20-hydroxyecdysone caused premature and incomplete ecdysis resulting in death. Tributyltin exaggerated this effect of exogenous 20-hydroxyecdysone. Further, exposure of daphnids to tributyltin enhanced the inductive effects of 20-hydroxyecdysone on expression of the 20-hydroxyecdysone-inducible gene HR3. Continuous, prolonged exposure of maternal daphnids to concentrations of tributyltin resulted in mortality concurrent with molting. Taken together, these results demonstrate that xenobiotics, such as tributyltin, can interact with RXR to influence gene expression regulated by the heterodimeric partner to RXR. The result of such interactions can be toxicity due to inappropriate or exaggerated hormonal signaling. The application of the in vitro/in vivo approach used in this study is discussed in relation to modeling of nonadditive interactions among constituents of chemical mixtures.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Wang, Ying H. and Kwon, Gwijun and Li, Hong and LeBlanc, Gerald A.}, year={2011}, month={Sep}, pages={71–79} }
 @article{hannas_das_li_leblanc_2010, title={Intracellular Conversion of Environmental Nitrate and Nitrite to Nitric Oxide with Resulting Developmental Toxicity to the Crustacean Daphnia magna}, volume={5}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0012453}, DOI={10.1371/journal.pone.0012453}, abstractNote={Background Nitrate and nitrite (jointly referred to herein as NOx) are ubiquitous environmental contaminants to which aquatic organisms are at particularly high risk of exposure. We tested the hypothesis that NOx undergo intracellular conversion to the potent signaling molecule nitric oxide resulting in the disruption of endocrine-regulated processes. Methodology/Principal Findings These experiments were performed with insect cells (Drosophila S2) and whole organisms Daphnia magna. We first evaluated the ability of cells to convert nitrate (NO3 −) and nitrite (NO2 −) to nitric oxide using amperometric real-time nitric oxide detection. Both NO3 − and NO2 − were converted to nitric oxide in a substrate concentration-dependent manner. Further, nitric oxide trapping and fluorescent visualization studies revealed that perinatal daphnids readily convert NO2 − to nitric oxide. Next, daphnids were continuously exposed to concentrations of the nitric oxide-donor sodium nitroprusside (positive control) and to concentrations of NO3 − and NO2 −. All three compounds interfered with normal embryo development and reduced daphnid fecundity. Developmental abnormalities were characteristic of those elicited by compounds that interfere with ecdysteroid signaling. However, no compelling evidence was generated to indicate that nitric oxide reduced ecdysteroid titers. Conclusions/Significance Results demonstrate that nitrite elicits developmental and reproductive toxicity at environmentally relevant concentrations due likely to its intracellular conversion to nitric oxide.}, number={8}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Hannas, Bethany R. and Das, Parikshit C. and Li, Hong and LeBlanc, Gerald A.}, editor={Pan, XiaopingEditor}, year={2010}, month={Aug}, pages={e12453} }
 @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} }
 @article{li_errington_foegeding_1999, title={Isostrength comparison of large-strain (fracture) rheological properties of egg white and whey protein gels}, volume={64}, ISSN={["0022-1147"]}, DOI={10.1111/j.1365-2621.1999.tb15935.x}, abstractNote={ABSTRACT:}, number={5}, journal={JOURNAL OF FOOD SCIENCE}, author={Li, H and Errington, AD and Foegeding, EA}, year={1999}, pages={893–898} }
 @inbook{fischer_li_li_choe_wright_rochelle_adler_1998, title={Intracellular regulation of airway mucin secretion.}, booktitle={Cilia, mucus and mucociliary interactions}, author={Fischer, B. M. and Li, C. and Li, H. and Choe, N. and Wright, D. T. and Rochelle, L. G. and Adler, K. B.}, year={1998}, pages={143–151} }
 @article{li_adler_1996, title={Histamine stimulates secretion of mucin and activates phospholipase C in airway epithelium: evidence for independent pathways.}, volume={153}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Li, H. and Adler, K. B.}, year={1996}, pages={A539} }
 @article{adler_wright_li_li_choe_rochell_fischer_1996, title={Nitric oxide: A key signaling molecule regulating airway mucin secretion.}, volume={9}, journal={Proceedings of the 9th World Congress on Bronchology & World Congress on Bronchoesophagology.}, author={Adler, K. B. and Wright, D. T. and Li, C. and Li, H. and Choe, N. and Rochell, L. G. and Fischer, B. M.}, year={1996}, pages={S060} }
 @article{fischer_wright_li_li_cohn_akley_adler_1995, title={Endogenously-generated nitric oxide (NO) may be a key signaling molecule in hypersecretion of mucin by guinea pig tracheal epithelial (GPTE) cells in vitro.}, volume={151}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Fischer, B. M. and Wright, D. T. and Li, H. and Li, C. M. and Cohn, L. A. and Akley, N. J. and Adler, K. B.}, year={1995}, pages={A337} }
 @article{li_choe_wright_adler_1995, title={HISTAMINE PROVOKES TURNOVER OF INOSITOL PHOSPHOLIPIDS IN GUINEA-PIG AND HUMAN AIRWAY EPITHELIAL-CELLS VIA AN H-1-RECEPTOR G-PROTEIN-DEPENDENT MECHANISM}, volume={12}, ISSN={["1044-1549"]}, DOI={10.1165/ajrcmb.12.4.7695921}, abstractNote={Guinea pig tracheal epithelial cells in primary air/liquid interface culture (GPTE) and virally transformed human bronchial epithelial cells (BEAS-2B) were exposed to histamine at concentrations of 1 to 100 microM. At concentrations greater than 1 microM, histamine elicited a concentration-dependent increase in accumulation of inositol phosphates in both cell types, as assessed by anion exchange chromatography. The effects of histamine were most pronounced at 15 to 30 min and were attenuated by the H1-receptor antagonist, pyrilamine. The H2-receptor antagonist, ranitidine, was without effect. Sodium fluoride (25 mM), a non-receptor-associated activator of GTP binding (G) proteins, increased accumulation of inositol phosphates within GPTE and BEAS cells. In cells permeabilized with digitonin, the nonhydrolyzable GTP analog, guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S; 10 microM) increased inositol phosphate accumulation. This GTP gamma S-induced increase was attenuated by exposure to 500 microM guanosine-5'-O-(2-thiodiphosphate) (GDP beta S). Additionally, histamine-induced increases in inositol phosphate accumulation were potentiated by GTP gamma S and attenuated by GDP beta S. These data indicate involvement of a G protein in the response to histamine. Preincubation with pertussis toxin (100 ng/ml for 4 h) did not significantly affect the response, suggesting that the associated G protein was not pertussis toxin-sensitive. The presence of the phosphatidylinositol-specific phospholipase C (PI-PLC)-associated G protein, G alpha q/11, and the presence of mRNA for the Gq family, were ascertained by immunoblotting and Northern hybridization, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)}, number={4}, journal={AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY}, author={LI, HF and CHOE, NH and WRIGHT, DT and ADLER, KB}, year={1995}, month={Apr}, pages={416–424} }
 @article{adler_fischer_li_choe_wright_1995, title={HYPERSECRETION OF MUCIN IN RESPONSE TO INFLAMMATORY MEDIATORS BY GUINEA-PIG TRACHEAL EPITHELIAL-CELLS IN-VITRO IS BLOCKED BY INHIBITION OF NITRIC-OXIDE SYNTHASE}, volume={13}, ISSN={["1044-1549"]}, DOI={10.1165/ajrcmb.13.5.7576687}, abstractNote={Primary cultures of guinea pig tracheal epithelial cells in air/liquid interface were exposed to one of four agents associated with airway inflammation: the peptide histamine (100 microM), the lipid mediator platelet-activating factor (1 microM), the cytokine tumor necrosis factor-alpha (15 ng/ml; specific activity 2.86 x 10(7) U/mg), or enzymatically generated reactive oxygen species (purine [500 microM]+xanthine oxidase [20 mU/ml]). Effects of each of these substances on release of mucin by guinea pig tracheal epithelial (GPTE) cells were measured using a monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA). Each secretagogue significantly enhanced release of mucin, but the stimulatory effect of each was inhibited by pre-(+)co-incubation of the cells with the competitive inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (L-NMA), but not by NG-monomethyl-D-arginine (D-NMA), the inactive stereoisomer that does not inhibit nitric oxide synthase. Neither L-NMA nor D-NMA affected mucin secretion by themselves. The results suggest that each of these inflammation-associated mediators provokes airway epithelial mucin secretion via a mechanism involving intracellular production of nitric oxide (NO) as a critical signaling molecule.}, number={5}, journal={AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY}, author={ADLER, KB and FISCHER, BM and LI, HF and CHOE, NH and WRIGHT, DT}, year={1995}, month={Nov}, pages={526–530} }
 @article{wright_cohn_li_fischer_li_adler_1994, title={Interactions of oxygen radicals with airway epithelium.}, volume={102}, DOI={10.1289/ehp.94102s1085}, abstractNote={Reactive oxygen species (ROS) have been implicated in the pathogenesis of numerous disease processes. Epithelial cells lining the respiratory airways are uniquely vulnerable regarding potential for oxidative damage due to their potential for exposure to both endogenous (e.g., mitochondrial respiration, phagocytic respiratory burst, cellular oxidases) and exogenous (e.g., air pollutants, xenobiotics, catalase negative organisms) oxidants. Airway epithelial cells use several nonenzymatic and enzymatic antioxidant mechanisms to protect against oxidative insult. Nonenzymatic defenses include certain vitamins and low molecular weight compounds such as thiols. The enzymes superoxide dismutase, catalase, and glutatione peroxidase are major sources of antioxidant protection. Other materials associated with airway epithelium such as mucus, epithelial lining fluid, and even the basement membrane/extracellular matrix may have protective actions as well. When the normal balance between oxidants and antioxidants is upset, oxidant stress ensues and subsequent epithelial cell alterations or damage may be a critical component in the pathogenesis of several respiratory diseases. Oxidant stress may profoundly alter lung physiology including pulmonary function (e.g., forced expiratory volumes, flow rates, and maximal inspiratory capacity), mucociliary activity, and airway reactivity. ROS may induce airway inflammation; the inflammatory process may serve as an additional source of ROS in airways and provoke the pathophysiologic responses described. On a more fundamental level, cellular mechanisms in the pathogenesis of ROS may involve activation of intracellular signaling enzymes including phospholipases and protein kinases stimulating the release of inflammatory lipids and cytokines. Respiratory epithelium may be intimately involved in defense against, and pathophysiologic changes invoked by, ROS.}, number={11}, journal={Environmental Health Perspectives. Supplements}, author={Wright, D. T. and Cohn, L. A. and Li, H. and Fischer, B. M. and Li, C. M. and Adler, K. B.}, year={1994}, pages={85–90} }
 @article{choe_li_adler_1994, title={Platelet activating factor and histamine activate phospholipase C in  airway epithelial cells in vitro via a pertussis toxin sensitive G protein.}, volume={149}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Choe, N.-H. and Li, H. and Adler, K. B.}, year={1994}, pages={A985} }
 @article{wright_akley_li_fischer_adler_1994, title={Reactive oxygen species (ROS) activate phospholipase C in guinea pig and human airway epithelial cells in vitro.}, volume={149}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Wright, D. T. and Akley, N. J. and Li, H. and Fischer, B. M. and Adler, K. B.}, year={1994}, pages={A315} }