Frank A von Hippel

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• Branco, J. M., Hingst-Zaher, E., Dillon, D., Jordan-Ward, R., Siegrist, J., Fischer, J. D., Schiesari, L., von Hippel, F. A., & Buck, C. L. (2023). A novel method for extraction and quantification of feather triiodothyronine (T3) and application to ecotoxicology of Purple Martin (Progne subis). Environmental pollution (Barking, Essex : 1987), 332, 121943.
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  Seventy-three percent of aerial insectivore species of birds breeding in North America have declined in the past five years. This decline is even greater in migratory insectivorous species, which face stressors in both their breeding and non-breeding ranges. The Purple Martin (Progne subis) is an aerial insectivore swallow that overwinters in South America and migrates to North America to breed. Purple Martin populations have declined by an estimated 25% since 1966. The eastern subspecies (P. subis subis) has declined the most and overwinters in the Amazon Basin, a region rich in environmental mercury (Hg) contamination. Previous studies reported elevated levels of Hg in feathers of this subspecies, which correlated negatively with body mass and fat reserves. Given the propensity of Hg to disrupt the endocrine system, and the role of thyroid hormones in regulating fat metabolism, this study quantifies concentrations of Hg and the thyroid hormone triiodothyronine (T) in the feathers of P. subis subis. To our knowledge, this is the first study to extract and quantify T in feathers; thus, we developed, tested, and optimized a method for extracting T from feather tissue and validated an enzyme immunoassay (EIA) to quantify T in Purple Martin feathers. The developed method yielded acceptable results for both parallelism and accuracy. The observed T concentrations were statistically modeled along with total Hg (THg) concentrations, but these variables were not significantly correlated. This suggests that the observed variation in THg concentration may be insufficient to cause a discernible change in T concentration. Furthermore, the observed effect of breeding location on feather T concentration might have obscured any effect of Hg.
• David, G. K., Hunter, A. H., Moromizato, K. H., Allen, C. M., Wheatley, R., von Hippel, F. A., Niehaus, A. C., & Wilson, R. S. (2023). Pre-cleaning of hair is not beneficial in LA-ICP-MS studies of chronic metal exposure. PloS one, 18(8), e0289635.
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  Chronic exposure to toxic metals is a serious global health concern. However, population-wide biomonitoring is costly and carries several sampling constraints. Though hair sampling can be a useful way to assess environmental exposure, external contamination is a long-standing concern, and a pre-cleaning step prior to metal quantification has long been recommended despite a lack of evidence for its efficacy. In this study, we quantified the spatial distribution of 16 elements in unwashed human hair samples using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS), then tested how two common pre-cleaning treatments (Triton-ethanol, Triton-nitric acid) affected metal content in external and interior layers of hair using LA-ICP-MS. We show that elements differ in their spatial distribution across hair and that pre-cleaning is not consistent in its effect on element concentrations and decreases interior concentrations of some elements. We demonstrate that differences among individuals can be quantified reliably with LA-ICP-MS analysis of interior concentrations of unwashed hair. Our study tests the widespread notion that pre-cleaning is essential in analyses of hair for environmental exposure to metals, and examines the benefits of a unified approach to analysis of metals in hair using LA-ICP-MS.
• Muncke, J., Andersson, A. M., Backhaus, T., Belcher, S. M., Boucher, J. M., Carney Almroth, B., Collins, T. J., Geueke, B., Groh, K. J., Heindel, J. J., von Hippel, F. A., Legler, J., Maffini, M. V., Martin, O. V., Peterson Myers, J., Nadal, A., Nerin, C., Soto, A. M., Trasande, L., , Vandenberg, L. N., et al. (2023). A vision for safer food contact materials: Public health concerns as drivers for improved testing. Environment international, 180, 108161.
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  Food contact materials (FCMs) and food contact articles are ubiquitous in today's globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. To identify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs.
• Baldwin, J. A., Trotter, R. T., Remiker, M., Buck, C. L., Aguirre, A., Milner, T., Torres, E., & Von Hippel, F. A. (2021). A community-engaged approach to environmental health research: process and lessons learned. Progress in Community Health Partnerships: Research, Education, and Action, 15(4), 533-540. doi:10.1353/cpr.2021.0043
• Credo, J., Chandos, A., Checinski, C., von Hippel, F. A., & Ingram, J. C. (2021). Sample preparation method for metal(loid) contaminant quantitation in rodent hair collected in Yuma County, Arizona. Environmental monitoring and assessment, 193(8), 522.
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  Yuma County, Arizona, is a large agricultural hub of the USA located in the southwestern corner of Arizona on the USA-Mexico border. Year-round use of agrichemicals at a massive scale along with the influx of aquatic contaminants in the Colorado River led to significant levels of environmental pollution and hence exposure risks for people and wildlife. Although hair is a recognized biomarker for metal exposure, there is no universal hair preparation protocol. This study evaluated two digestion methods for metal quantitation using inductively coupled plasma-mass spectrometry (ICP-MS) and three methods for mercury quantitation using cold vapor-atomic absorption spectroscopy (CV-AAS), both employing certified reference materials. The "overnight" and "heating" digestion methods were suitable for ICP-MS, while only the heating method was suitable for CV-AAS. These validated methods will be useful for a variety of human and wildlife assessments of toxic metal(loid) exposure.
• Minicozzi, M. R., Axlid, E. G., von Hippel, F. A., Espinoza, J., Funke, A., Phillips, Q. P., & Buck, C. L. (2021). Perchlorate exposure does not induce obesity or non-alcoholic fatty liver disease in zebrafish. PloS one, 16(8), e0254500.
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  Perchlorate is a water-soluble contaminant found throughout the United States and many other countries. Perchlorate competitively inhibits iodide uptake at the sodium/iodide symporter, reducing thyroid hormone synthesis, which can lead to hypothyroidism and metabolic syndromes. Chronic perchlorate exposure induces hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) in developing threespine stickleback (Gasterosteus aculeatus). We hypothesized that perchlorate would also induce zebrafish (Danio rerio) to develop phenotypes consistent with NAFLD and to accumulate lipids throughout the body. We exposed zebrafish embryos to four concentrations of perchlorate treated water (10μg/L, 10mg/L, 30mg/L, and 100mg/L) and a control (0mg/L) over the course of 133 days. Adult zebrafish were euthanized, sectioned, H&E and Oil Red-O stained, and analyzed for liver morphology and whole body lipid accumulation. In a representative section of the liver, we counted the number of lipid droplets and measured the area of each droplet and the total lipid area. For whole body analysis, we calculated the ratio of lipid area to body area within a section. We found that zebrafish exposed to perchlorate did not differ in any measured liver variables or whole body lipid area when compared to controls. In comparison to stickleback, we see a trend that control stickleback accumulate more lipids in their liver than do control zebrafish. Differences between the species indicate that obesogenic effects due to perchlorate exposure are not uniform across fish species, and likely are mediated by evolutionary differences related to geographic location. For example, high latitude fishes such as stickleback evolved to deposit lipid stores for over-winter survival, which may lead to more pronounced obesogenic effects than seen in tropical fish such as zebrafish.
• Pan, Q., Feron, R., Jouanno, E., Darras, H., Herpin, A., Koop, B., Rondeau, E., Goetz, F. W., Larson, W. A., Bernatchez, L., Tringali, M., Curran, S. S., Saillant, E., Denys, G. P., von Hippel, F. A., Chen, S., López, J. A., Verreycken, H., Ocalewicz, K., , Guyomard, R., et al. (2021). The rise and fall of the ancient northern pike master sex-determining gene. eLife, 10.
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  The understanding of the evolution of variable sex determination mechanisms across taxa requires comparative studies among closely related species. Following the fate of a known master sex-determining gene, we traced the evolution of sex determination in an entire teleost order (Esociformes). We discovered that the northern pike () master sex-determining gene originated from a 65 to 90 million-year-old gene duplication event and that it remained sex linked on undifferentiated sex chromosomes for at least 56 million years in multiple species. We identified several independent species- or population-specific sex determination transitions, including a recent loss of a Y chromosome. These findings highlight the diversity of evolutionary fates of master sex-determining genes and the importance of population demographic history in sex determination studies. We hypothesize that occasional sex reversals and genetic bottlenecks provide a non-adaptive explanation for sex determination transitions.
• Roberts Kingman, G. A., Vyas, D. N., Jones, F. C., Brady, S. D., Chen, H. I., Reid, K., Milhaven, M., Bertino, T. S., Aguirre, W. E., Heins, D. C., von Hippel, F. A., Park, P. J., Kirch, M., Absher, D. M., Myers, R. M., Di Palma, F., Bell, M. A., Kingsley, D. M., & Veeramah, K. R. (2021). Predicting future from past: The genomic basis of recurrent and rapid stickleback evolution. Science advances, 7(25).
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  Similar forms often evolve repeatedly in nature, raising long-standing questions about the underlying mechanisms. Here, we use repeated evolution in stickleback to identify a large set of genomic loci that change recurrently during colonization of freshwater habitats by marine fish. The same loci used repeatedly in extant populations also show rapid allele frequency changes when new freshwater populations are experimentally established from marine ancestors. Marked genotypic and phenotypic changes arise within 5 years, facilitated by standing genetic variation and linkage between adaptive regions. Both the speed and location of changes can be predicted using empirical observations of recurrence in natural populations or fundamental genomic features like allelic age, recombination rates, density of divergent loci, and overlap with mapped traits. A composite model trained on these stickleback features can also predict the location of key evolutionary loci in Darwin's finches, suggesting that similar features are important for evolution across diverse taxa.
• Trotter Ii, R., Baldwin, J., Buck, C. L., Remiker, M., Aguirre, A., Milner, T., Torres, E., & von Hippel, F. A. (2021). Health Impacts of Perchlorate and Pesticide Exposure: Protocol for Community-Engaged Research to Evaluate Environmental Toxicants in a US Border Community. JMIR research protocols, 10(8), e15864.
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  The Northern Arizona University (NAU) Center for Health Equity Research (CHER) is conducting community-engaged health research involving "environmental scans" in Yuma County in collaboration with community health stakeholders, including the Yuma Regional Medical Center (YRMC), Regional Center for Border Health, Inc. (RCBH), Campesinos Sin Fronteras (CSF), Yuma County Public Health District, and government agencies and nongovernmental organizations (NGOs) working on border health issues. The purpose of these efforts is to address community-generated environmental health hazards identified through ongoing coalitions among NAU, and local health care and research institutions.