@article{rock_polera_guillette_starnes_dean_watters_stevens-stewart_belcher_2023, title={Domestic Dogs and Horses as Sentinels of Per- and Polyfluoroalkyl Substance Exposure and Associated Health Biomarkers in Gray's Creek North Carolina}, volume={57}, ISSN={["1520-5851"]}, url={https://doi.org/10.1021/acs.est.3c01146}, DOI={10.1021/acs.est.3c01146}, abstractNote={Central North Carolina (NC) is highly contaminated with per- and polyfluoroalkyl substances (PFAS), in part due to local fluorochemical production. Little is known about the exposure profiles and long-term health impacts for humans and animals that live in nearby communities. In this study, serum PFAS concentrations were determined using liquid chromatography high-resolution mass spectrometry and diagnostic clinical chemistry endpoints were assessed for 31 dogs and 32 horses that reside in Gray's Creek NC at households with documented PFAS contamination in their drinking water. PFAS were detected in every sample, with 12 of the 20 PFAS detected in ≥50% of samples from each species. The average total PFAS concentrations in horses were lower compared to dogs who had higher concentrations of PFOS (dogs 2.9 ng/mL; horses 1.8 ng/mL), PFHxS (dogs 1.43 ng/mL, horses < LOD), and PFOA (dogs 0.37 ng/mL; horses 0.10 ng/mL). Regression analysis highlighted alkaline phosphatase, glucose, and globulin proteins in dogs and gamma glutamyl transferase in horses as potential biomarkers associated with PFAS exposure. Overall, the results of this study support the utility of companion animal and livestock species as sentinels of PFAS exposure differences inside and outside of the home. As in humans, renal and hepatic health in domestic animals may be sensitive to long-term PFAS exposures.}, number={26}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY}, author={Rock, Kylie D. and Polera, Madison E. and Guillette, Theresa C. and Starnes, Hannah M. and Dean, Kentley and Watters, Mike and Stevens-Stewart, Debra and Belcher, Scott M.}, year={2023}, month={Jun}, pages={9567–9579} } @article{guillette_jackson_guillette_mccord_belcher_2022, title={Blood concentrations of per- and polyfluoroalkyl substances are associated with autoimmune-like effects in American alligators from Wilmington, North Carolina}, volume={4}, ISSN={["2673-3080"]}, url={http://dx.doi.org/10.3389/ftox.2022.1010185}, DOI={10.3389/ftox.2022.1010185}, abstractNote={Surface and groundwater of the Cape Fear River basin in central and coastal North Carolina is contaminated with high levels of per- and polyfluoroalkyl substances (PFAS). Elevated levels of PFAS have also been found in blood of fish and wildlife from the Cape Fear River, and in the blood of human populations reliant on contaminated well or surface water from the Cape Fear River basin as a source of drinking water. While the public and environmental health impacts of long-term PFAS exposures are poorly understood, elevated blood concentrations of some PFAS are linked with immunotoxicity and increased incidence of some chronic autoimmune diseases in human populations. The goal of this One Environmental Health study was to evaluate PFAS exposure and biomarkers related to immune health in populations of American alligators (Alligator mississippiensis), a protected and predictive sentinel species of adverse effects caused by persistent toxic pollutants. We found that serum PFAS concentrations in alligator populations from the Cape Fear River were increased compared to a reference population of alligators from the adjoining Lumber River basin. The elevated serum PFAS concentrations in the Cape Fear River alligators were associated with increased innate immune activities, and autoimmune-like phenotypes in this population. In addition to evidence of significantly higher double stranded-DNA binding autoantibodies in adult Cape Fear River alligators, our qRT-PCR analysis found remarkably high induction of Interferon-α signature genes implicated in the pathology of human autoimmune disease. We interpret the association of increased PFAS exposure with disrupted immune functions to suggest that PFAS broadly alters immune activities resulting in autoimmune-like pathology in American alligators. This work substantiates and extends evidence from experimental models and human epidemiology studies showing that some PFAS are immune toxicants.}, journal={FRONTIERS IN TOXICOLOGY}, publisher={Frontiers Media SA}, author={Guillette, T. C. and Jackson, Thomas W. and Guillette, Matthew and McCord, James and Belcher, Scott M.}, year={2022}, month={Oct} } @article{sara_luus-powell_fogelson_botha_guillette_smit_hoffman_kunutu_koelmel_bowden_2020, title={A histological evaluation of pansteatitis-affected Mozambique tilapia,Oreochromis mossambicus(Peters 1852), from different geographical locations in South Africa}, volume={43}, ISSN={["1365-2761"]}, DOI={10.1111/jfd.13184}, abstractNote={AbstractPansteatitis is the leading cause for the decline in Nile crocodile populations and the sporadic mortality of fish in the Olifants River System, South Africa. To determine the prevalence of this disease in lentic systems, Mozambique tilapia, Oreochromis mossambicus, were collected from Lake Loskop, Lake Flag Boshielo, Phalaborwa Barrage and Lake Luphephe‐Nwanedi. The former three impoundments are located within the main stem of the Olifants River, while the latter, which is geographically isolated and situated in the Limpopo River System, served as a reference site. Mesenteric adipose, liver, serosa of the swim bladder, gill and the skeletal muscle of fish sampled were examined for gross and microscopic evidence of pansteatitis. Microscopically observed changes were used to statistically compare pansteatitis prevalence between samples and sites. Based on histopathological evaluation, the adipose tissue in the liver, swim bladder serosa and coelom from severely debilitated individuals showed the most significant pathological changes. Lesions indicative of steatitis were observed in fish collected from Lake Loskop (75%), Lake Flag Boshielo (22%) and Lake Luphephe‐Nwanedi (15%). Further investigation is warranted to understand the pervasiveness and mechanisms driving pathological changes of pansteatitis at Lake Flag Boshielo, Phalaborwa Barrage and Lake Luphephe‐Nwanedi.}, number={10}, journal={JOURNAL OF FISH DISEASES}, author={Sara, Joseph R. and Luus-Powell, Wilmien J. and Fogelson, Susan B. and Botha, Hannes and Guillette, Theresa C. and Smit, Willem J. and Hoffman, Andre and Kunutu, Katlego D. and Koelmel, Jeremy P. and Bowden, John A.}, year={2020}, month={Oct}, pages={1185–1199} } @article{guillette_mccord_guillette_polera_rachels_morgeson_kotlarz_knappe_reading_strynar_et al._2020, title={Elevated levels of per- and polyfluoroalkyl substances in Cape Fear River Striped Bass (Morone saxatilis) are associated with biomarkers of altered immune and liver function}, volume={136}, ISSN={["1873-6750"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85079172705&partnerID=MN8TOARS}, DOI={10.1016/j.envint.2019.105358}, abstractNote={Per- and polyfluoroalkyl substances (PFAS) are anthropogenic chemicals of concern that persist in the environment. Environmental monitoring revealed high concentrations of hexafluoropropylene oxide dimer acid (HFPO-DA) and other novel PFAS in the lower Cape Fear River; however, there is limited information on PFAS exposures and effects of this contamination on aquatic biota. Serum concentrations of 23 PFAS in Striped Bass (Morone saxatilis) from the Cape Fear River (n = 58) and a reference population from an aquaculture laboratory on the Pamlico/Tar watershed (n = 29) were quantified using liquid chromatography and high-resolution mass spectrometry, and correlations between PFAS concentrations and health-related serum biomarkers were evaluated. Perfluorooctane sulfonate, the predominant PFAS in Cape Fear River Striped Bass serum, was detectable in every sample with serum concentrations reaching 977 ng/mL. Perfluorononanoic and perfluorodecanoic acid were also detected in all samples, with perfluorohexanesulfonic acid present in >98% of the samples. HFPO-DA (range <0.24-5.85 ng/mL) and Nafion byproduct 2 (range <0.2-1.03 ng/mL) were detected in 48% and 78% of samples, respectively. The mean total PFAS concentration found in domestic Striped Bass raised in well-water under controlled aquaculture conditions was 40 times lower, with HPFO-DA detected in 10% of the samples, and Nafion byproduct 2 was not detected. The elevated PFAS concentrations found in the Cape Fear River Striped Bass were associated with biomarkers of alterations in the liver and immune system.}, journal={ENVIRONMENT INTERNATIONAL}, author={Guillette, T. C. and McCord, James and Guillette, Matthew and Polera, M. E. and Rachels, Kyle T. and Morgeson, Clint and Kotlarz, Nadine and Knappe, Detlef R. U. and Reading, Benjamin J. and Strynar, Mark and et al.}, year={2020}, month={Mar} } @article{koelmel_ulmer_fogelson_jones_botha_bangma_guillette_luus-powell_sara_smit_et al._2019, title={Lipidomics for wildlife disease etiology and biomarker discovery: a case study of pansteatitis outbreak in South Africa}, volume={15}, ISSN={["1573-3890"]}, DOI={10.1007/s11306-019-1490-9}, abstractNote={Lipidomics is an emerging field with great promise for biomarker and mechanistic studies due to lipids diverse biological roles. Clinical research applying lipidomics is drastically increasing, with research methods and tools developed for clinical applications equally promising for wildlife studies. Limited research to date has applied lipidomics, especially of the intact lipidome, to wildlife studies. Therefore, we examine the application of lipidomics for in situ studies on Mozambique tilapia (Oreochromis mossambicus) in Loskop Dam, South Africa. Wide-scale mortality events of aquatic life associated with an environmentally-derived inflammatory disease, pansteatitis, have occurred in this area. The lipidome of adipose tissue (n = 31) and plasma (n = 51) from tilapia collected from Loskop Dam were characterized using state of the art liquid chromatography coupled to high-resolution tandem mass spectrometry. Lipid profiles reflected pansteatitis severity and were significantly different between diseased and healthy individuals. Over 13 classes of lipids associated with inflammation, cell death, and/or oxidative damage were upregulated in pansteatitis-affected adipose tissue, including ether-lipids, short-chained triglyceride oxidation products, sphingolipids, and acylcarnitines. Ceramides showed a 1000-fold increase in the most affected adipose tissues and were sensitive to disease severity. In plasma, triglycerides were found to be downregulated in pansteatitis-affected tilapia. Intact lipidomics provided useful mechanistic data and possible biomarkers of pansteatitis. Lipids pointed to upregulated inflammatory pathways, and ceramides serve as promising biomarker candidates for pansteatitis. As comprehensive coverage of the lipidome aids in the elucidation of possible disease mechanisms, application of lipidomics could be applied to the understanding of other environmentally-derived inflammatory conditions, such as those caused by obesogens.}, number={3}, journal={METABOLOMICS}, author={Koelmel, Jeremy P. and Ulmer, Candice Z. and Fogelson, Susan and Jones, Christina M. and Botha, Hannes and Bangma, Jacqueline T. and Guillette, Theresa C. and Luus-Powell, Wilmien J. and Sara, Joseph R. and Smit, Willem J. and et al.}, year={2019}, month={Mar} } @article{guillette_jackson_belcher_2018, title={Duality of estrogen receptor beta action in cancer progression}, volume={41}, ISSN={["1471-4973"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85047091078&partnerID=MN8TOARS}, DOI={10.1016/j.coph.2018.05.001}, abstractNote={The physiological actions of estrogens are primarily mediated by the nuclear hormone receptors estrogen receptor alpha (ERα) and beta (ERβ). Activities of these nuclear steroid hormone receptors in etiology and progression of many hormone-responsive cancers are well-established, yet the specific role of each receptor, and their various expressed isoforms, in estrogen-responsive cancers remains unclear. Recent advances in nuclear receptor profiling, characterization of expressed splice variants, and the availability of new experimental cancer models, has extended the understanding of the complex interplay between the differentially expressed nuclear estrogen receptors. In this review, we discuss proposed roles of ERβ in several subtypes of cancers that lack significant ERα expression and define current understanding of how different ERs collaborate to regulate cellular processes.}, journal={CURRENT OPINION IN PHARMACOLOGY}, author={Guillette, T. C. and Jackson, Thomas W. and Belcher, Scott M.}, year={2018}, month={Aug}, pages={66–73} }