@article{ansari_hughes_husain_2016, title={Ligand-Mediated Toxicology: Characterization and Translational Prospects}, ISBN={["978-3-319-27447-8"]}, ISSN={["2168-4219"]}, DOI={10.1007/978-3-319-27449-2_4}, abstractNote={In biochemistry a ligand is a molecule that binds to a receptor or other biomolecule that forms a complex and produces a biological effect. We live in a world of exposure to exogenous ligands and there are three long-established strands of biological research that have investigated the actions of biologically active dietary or environmental compounds on animals, including humans. First, in agricultural and animal husbandry research, there is extensive documentation of the many thousands of phytochemicals that mediate plant-animal interactions many of which produce toxic effects at certain levels of exposure in terms of dose, duration and window of sensitivity. In a broader biological context, many of these relationships have been formalized by concepts of co-evolution of plants and animals. Second, there is a long history of toxicology research showing a wide range of adverse effects that often result from exposures to hormones and other modulators of endocrine function, especially during developmentally sensitive intervals. In recent decades much of this research has been encapsulated by a single term of “endocrine disruptors” even though many ligand-mediated actions are not endocrine per se or definitively adverse. Third, nutritional and functional foods research have demonstrated a wide range of health benefits produced by consumption of many phytochemical ligands through mechanisms that are not truly distinct from those that seem to mediate the adverse effects noted in either the animal husbandry or developmental toxicology research arenas. We are confident that environmental and public health can be enhanced by defining how such exposures to exogenous signaling molecules (ligands) pose both risks and benefits. Therefore, it is time to modify the scientific perspective and nomenclature to encompass these several streams of investigation such that both risks and benefits of exposure to dietary and environmental ligands may be characterized and translated into sound strategies to address environmental and public health concerns. Fetal alcohol spectrum disorder (FASD) is an illustrative case for translational toxicology-informed interventions where there is a viable prospect for a multi-component nutritional health benefit to reduce occurrence or severity of FASD. Health promoting interventional options must include reduction(s) in exposures to ligands that incur health risks but when exposures cannot be adequately reduced or preempted, we should also define and employ active mechanistically-based mitigative interventions.}, journal={TRANSLATIONAL TOXICOLOGY: DEFINING A NEW THERAPEUTIC DISCIPLINE}, author={Ansari, Rais and Hughes, Claude L. and Husain, Kazim}, year={2016}, pages={113–137} }
 @article{hughes_waters_allen_obasanjo_2016, title={The Opportunity to Translate Developmental Toxicology into a Therapeutic Discipline}, ISBN={["978-3-319-27447-8"]}, ISSN={["2168-4219"]}, DOI={10.1007/978-3-319-27449-2_1}, abstractNote={Since presentation of our view of translational developmental toxicology in 2013, numerous investigations from a wide range of approaches have added to the evidence underlying our core premise; namely that as the potential adverse developmental effects from a range of exposures are progressively defined, preventative or mitigative therapies can be conceived, assessed and ethically implemented. The spectrum of studies reported in recent years span a wide range of exposure categories and various developmental outcomes ranging from molecular and cellular to the organismal level up to and including human behavior. Since human exposures to chemicals, physical agents and social factors are inevitable, the human fetus is subject to effects that can have lifelong consequences. In order to apply the translational concept to developmental toxicology, established or potential therapeutic obstetrical, neonatal, childhood and adolescent interventions will be required. Those that undergo testing during developmentally sensitive intervals will likely derive from generally-regarded-as-safe (GRAS) or well-established/repurposed pharmaceutical options. Ultimately if we are to translate environmental health discoveries into safe and effective interventions, we must assert and characterize valid, applicable therapies such as GRAS treatments and eventually “ethical pharmaceuticals” for the protective care of these highly vulnerable young people. We can create a safe and efficacious environmental health portfolio of interventional options to improve human health that include both reduction/avoidance of exposure and specific preventative/mitigative/restorative therapeutics. In this chapter we will broadly update new insights that have been gained over the last 2 years regarding the progress of translational developmental toxicology toward becoming a therapeutic discipline.}, journal={TRANSLATIONAL TOXICOLOGY: DEFINING A NEW THERAPEUTIC DISCIPLINE}, author={Hughes, Claude L. and Waters, Michael D. and Allen, David and Obasanjo, Iyabo}, year={2016}, pages={3–44} }
 @article{gannon_sadeu_agarwal_hughes_foster_2014, title={Cigarette smoking and ovarian function}, journal={Ovarian Toxicology, 2nd Edition}, author={Gannon, A. M. and Sadeu, J. C. and Agarwal, S. K. and Hughes, C. L. and Foster, W. G.}, year={2014}, pages={229–248} }
 @article{hendrix_hughes_selgrade_2014, title={Modeling Endocrine Control of the Pituitary-Ovarian Axis: Androgenic Influence and Chaotic Dynamics}, volume={76}, ISSN={["1522-9602"]}, DOI={10.1007/s11538-013-9913-7}, abstractNote={Mathematical models of the hypothalamus-pituitary-ovarian axis in women were first developed by Schlosser and Selgrade in 1999, with subsequent models of Harris-Clark et al. (Bull. Math. Biol. 65(1):157-173, 2003) and Pasteur and Selgrade (Understanding the dynamics of biological systems: lessons learned from integrative systems biology, Springer, London, pp. 38-58, 2011). These models produce periodic in-silico representation of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), progesterone (P4), inhibin A (InhA), and inhibin B (InhB). Polycystic ovarian syndrome (PCOS), a leading cause of cycle irregularities, is seen as primarily a hyper-androgenic disorder. Therefore, including androgens into the model is necessary to produce simulations relevant to women with PCOS. Because testosterone (T) is the dominant female androgen, we focus our efforts on modeling pituitary feedback and inter-ovarian follicular growth properties as functions of circulating total T levels. Optimized parameters simultaneously simulate LH, FSH, E2, P4, InhA, and InhB levels of Welt et al. (J. Clin. Endocrinol. Metab. 84(1):105-111, 1999) and total T levels of Sinha-Hikim et al. (J. Clin. Endocrinol. Metab. 83(4):1312-1318, 1998). The resulting model is a system of 16 ordinary differential equations, with at least one stable periodic solution. Maciel et al. (J. Clin. Endocrinol. Metab. 89(11):5321-5327, 2004) hypothesized that retarded early follicle growth resulting in "stockpiling" of preantral follicles contributes to PCOS etiology. We present our investigations of this hypothesis and show that varying a follicular growth parameter produces preantral stockpiling and a period-doubling cascade resulting in apparent chaotic menstrual cycle behavior. The new model may allow investigators to study possible interventions returning acyclic patients to regular cycles and guide developments of individualized treatments for PCOS patients.}, number={1}, journal={BULLETIN OF MATHEMATICAL BIOLOGY}, author={Hendrix, Angelean O. and Hughes, Claude L. and Selgrade, James F.}, year={2014}, month={Jan}, pages={136–156} }
 @article{li_zhu_niu_shi_hughes_tian_huang_2013, title={Effects of Dietary Chromium Methionine on Growth Performance, Carcass Composition, Meat Colour and Expression of the Colour-related Gene Myoglobin of Growing-finishing Pigs}, volume={26}, ISSN={["1976-5517"]}, DOI={10.5713/ajas.2013.13012}, abstractNote={To investigate the effect of dietary chromium (Cr) as Cr methionine (CrMet) on growth performance, carcass traits, pork quality, meat colour and expression of meat colour-related genes in growing-finishing pigs, 189 crossbred Duroc×(Landrace×Yorkshire) growing-finishing pigs (male, castrated, average initial BW 74.58±1.52 kg) were selected and randomly allocated into four groups. Dietary treatments per kg of feed were as follows: 0 (CT), 0.3 mg/kg (T1), 0.6 mg/kg (T2) and 0.9 mg/kg (T3) Cr (in the form of CrMet; as-fed basis), and each treatment was replicated five times with 8 to 10 pigs per replicate pen. During the 28 d of the experiment, both the ADG and the ADFI increased linearly (p<0.05) as the level of dietary Cr increased. The F/G ratio decreased linearly (p<0.05). As dietary Cr increased, loin muscle areas (linear, p = 0.013) and average backfat thickness (linear, p = 0.072) decreased. Shear force (linear, p = 0.070) and Commission Internationale de I’Éclairage (CIE) redness (quadratic, p = 0.028) were increased. In addition, CIE Lightness (quadratic, p = 0.053) were decreased as dietary Cr increased. As dietary Cr increased, total myglobin (Mb) content (quadratic, p = 0.015) and the mb mRNA levels (quadratic, p = 0.046) in longissimus muscles of pigs were up-regulated. In conclusion, supplementation of dietary Cr improved growth and meat colour, but increased shear force and decreased IMF reduced palatability of longissimus muscles. Moreover, the increasing total Mb content and mb mRNA levels indicated that CrMet dietary supplementation may improve meat colour via up-regulating expression of the mb gene.}, number={7}, journal={ASIAN-AUSTRALASIAN JOURNAL OF ANIMAL SCIENCES}, author={Li, Y. S. and Zhu, N. H. and Niu, P. P. and Shi, F. X. and Hughes, C. L. and Tian, G. X. and Huang, R. H.}, year={2013}, month={Jul}, pages={1021–1029} }