@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{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{kotlarz_mccord_collier_lea_strynar_lindstrom_wilkie_islam_matney_tarte_et al._2020, title={Measurement of Novel, Drinking Water-Associated PFAS in Blood from Adults and Children in Wilmington, North Carolina}, volume={128}, ISSN={["1552-9924"]}, DOI={10.1289/EHP6837}, abstractNote={Background: From 1980 to 2017, a fluorochemical manufacturing facility discharged wastewater containing poorly understood per- and polyfluoroalkyl substances (PFAS) to the Cape Fear River, the primary drinking water source for Wilmington, North Carolina, residents. Those PFAS included several fluoroethers including HFPO-DA also known as GenX. Little is known about the bioaccumulation potential of these fluoroethers. Objective: We determined levels of fluoroethers and legacy PFAS in serum samples from Wilmington residents. Methods: In November 2017 and May 2018, we enrolled 344 Wilmington residents ≥6 years of age into the GenX Exposure Study and collected blood samples. Repeated blood samples were collected from 44 participants 6 months after enrollment. We analyzed serum for 10 fluoroethers and 10 legacy PFAS using liquid chromatography–high-resolution mass spectrometry. Results: Participants’ ages ranged from 6 to 86 y, and they lived in the lower Cape Fear Region for 20 y on average (standard deviation: 16 y). Six fluoroethers were detected in serum; Nafion by-product 2 and PFO4DA were detected in >99% of participants. PFO3OA and NVHOS were infrequently detected. Hydro-EVE was present in a subset of samples, but we could not quantify it. GenX was not detected above our analytical method reporting limit (2 ng/mL). In participants with repeated samples, the median decrease in fluoroether levels ranged from 34% for Nafion byproduct 2 to 65% for PFO4DA in 6 months due to wastewater discharge control. Four legacy PFAS (PFHxS, PFOA, PFOS, PFNA) were detected in most (≥97%) participants; these levels were higher than U.S. national levels for the 2015–2016 National Health and Nutrition Examination Survey. The sum concentration of fluoroethers contributed 23% to participants’ summed PFAS (median: 25.0 ng/mL). Conclusion: Poorly understood fluoroethers released into the Cape Fear River by a fluorochemical manufacturing facility were detected in blood samples from Wilmington, North Carolina, residents. Health implications of exposure to these novel PFAS have not been well characterized. https://doi.org/10.1289/EHP6837}, number={7}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Kotlarz, Nadine and McCord, James and Collier, David and Lea, C. Suzanne and Strynar, Mark and Lindstrom, Andrew B. and Wilkie, Adrien A. and Islam, Jessica Y. and Matney, Katelyn and Tarte, Phillip and et al.}, year={2020}, month={Jul} }
 @article{mccord_muddiman_khaledi_2017, title={Perfluorinated alcohol induced coacervates as extraction media for proteomic analysis}, volume={1523}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2017.06.025}, abstractNote={We describe a novel method for using hexafluoroisopropanol (HFIP) induced coacervates with a variety of surfactants to extract proteins from a yeast whole cell lysate and conduct a global proteomic investigation on the extracted proteins. Yeast whole cell lysates were prepared and proteins were extracted using two workflows: 1) Proteins were extracted into the coacervate generated from the mixture of HFIP, surfactant, and cell lysate. 2) Proteins were extracted from cell lysate using a surfactant solution, and HFIP was added to the supernatant to generate a coacervate phase with concentrated proteins. Both initial extractions were followed by a modified filter-aided sample preparation (FASP) cleanup. The methodology yields significant protein concentrations in the coacervate phase (2–3 orders of magnitude increase in concentration) and an increase in proteome sequence coverage (+5%), membrane proteins identifications (+50%), and identification of proteins from low abundance cellular subfractions (>10% of total IDs).}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={McCord, James P. and Muddiman, David C. and Khaledi, Morteza G.}, year={2017}, month={Nov}, pages={293–299} }
 @article{mccord_sun_deutsch_moritz_muddiman_2017, title={The PeptideAtlas of the Domestic Laying Hen}, volume={16}, ISSN={["1535-3907"]}, DOI={10.1021/acs.jproteome.6b00952}, abstractNote={Proteomics-based biological research is greatly expanded by high-quality mass spectrometry studies, which are themselves enabled by access to quality mass spectrometry resources, such as high-quality curated proteome data repositories. We present a PeptideAtlas for the domestic chicken, containing an extensive and robust collection of chicken tissue and plasma samples with substantial value for the chicken proteomics community for protein validation and design of downstream targeted proteome quantitation. The chicken PeptideAtlas contains 6646 canonical proteins at a protein FDR of 1.3%, derived from ∼100 000 peptides at a peptide level FDR of 0.1%. The rich collection of readily accessible data is easily mined for the purposes of data validation and experimental planning, particularly in the realm of developing proteome quantitation workflows. Herein we demonstrate the use of the atlas to mine information on common chicken acute-phase proteins and biomarkers for cancer detection research, as well as their localization and polymorphisms. This wealth of information will support future proteome-based research using this highly important agricultural organism in pursuit of both chicken and human health outcomes.}, number={3}, journal={JOURNAL OF PROTEOME RESEARCH}, author={McCord, James and Sun, Zhi and Deutsch, Eric W. and Moritz, Robert L. and Muddiman, David C.}, year={2017}, month={Mar}, pages={1352–1363} }
 @article{hecht_mccord_muddiman_2016, title={A quantitative glycomics and proteomics combined purification strategy}, number={109}, journal={Jove-Journal of Visualized Experiments}, author={Hecht, E. S. and McCord, J. P. and Muddiman, D. C.}, year={2016} }
 @article{kazarian_rodriguez_deverell_mccord_muddiman_paull_2016, title={Wall modified photonic crystal fibre capillaries as porous layer open tubular columns for in-capillary micro-extraction and capillary chromatography}, volume={905}, ISSN={["1873-4324"]}, DOI={10.1016/j.aca.2015.10.005}, abstractNote={Wall modified photonic crystal fibre capillary columns for in-capillary micro-extraction and liquid chromatographic separations is presented. Columns contained 126 internal parallel 4 μm channels, each containing a wall bonded porous monolithic type polystyrene-divinylbenzene layer in open tubular column format (PLOT). Modification longitudinal homogeneity was monitored using scanning contactless conductivity detection and scanning electron microscopy. The multichannel open tubular capillary column showed channel diameter and polymer layer consistency of 4.2 ± 0.1 μm and 0.26 ± 0.02 μm respectively, and modification of 100% of the parallel channels with the monolithic polymer. The modified multi-channel capillaries were applied to the in-capillary micro-extraction of water samples. 500 μL of water samples containing single μg L−1 levels of polyaromatic hydrocarbons were extracted at a flow rate of 10 μL min−1, and eluted in 50 μL of acetonitrile for analysis using HPLC with fluorescence detection. HPLC LODs were 0.08, 0.02 and 0.05 μg L−1 for acenaphthene, anthracene and pyrene, respectively, with extraction recoveries of between 77 and 103%. The modified capillaries were also investigated briefly for direct application to liquid chromatographic separations, with the retention and elution of a standard protein (cytochrome c) under isocratic conditions demonstrated, proving chromatographic potential of the new column format, with run-to-run retention time reproducibility of below 1%.}, journal={ANALYTICA CHIMICA ACTA}, author={Kazarian, Artaches A. and Rodriguez, Estrella Sanz and Deverell, Jeremy A. and McCord, James and Muddiman, David C. and Paull, Brett}, year={2016}, month={Jan}, pages={1–7} }
 @article{hecht_mccord_muddiman_2015, title={Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans}, volume={87}, ISSN={["1520-6882"]}, DOI={10.1021/acs.analchem.5b01609}, abstractNote={High-throughput, quantitative processing of N-linked glycans would facilitate large-scale studies correlating the glycome with disease and open the field to basic and applied researchers. We sought to meet these goals by coupling filter-aided-N-glycan separation (FANGS) to the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) for analysis of plasma. A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. Furthermore, to increase the depth of glycome coverage, we executed a definitive screening design of experiments (DOE) to optimize the MS parameters for glycan analyses. We optimized MS parameters across five N-glycan responses using a standard glycan mixture, translated these to plasma and achieved up to a 3-fold increase in ion abundances.}, number={14}, journal={ANALYTICAL CHEMISTRY}, author={Hecht, Elizabeth S. and McCord, James P. and Muddiman, David C.}, year={2015}, month={Jul}, pages={7305–7312} }