@article{rose_bentley_maity_maguire_planchart_spasojevic_liu_thorp jr_hoyo_2024, title={Association between F2-isoprostanes and self-reported stressors in pregnant americans of African and European ancestry}, volume={10}, ISSN={["2405-8440"]}, DOI={10.1016/j.heliyon.2024.e25578}, abstractNote={BackgroundPoor birth outcomes such as preterm birth/delivery disproportionately affect African Americans compared to White individuals. Reasons for this disparity are likely multifactorial, and include prenatal psychosocial stressors, and attendant increased lipid peroxidation; however, empirical data linking psychosocial stressors during pregnancy to oxidative status are limited.MethodsWe used established scales to measure five psychosocial stressors. Maternal adverse childhood experiences, financial stress, social support, anxiety, and depression were measured among 50 African American and White pregnant women enrolled in the Stress and Health in Pregnancy cohort. Liquid chromatography‐tandem mass spectrometry was used to measure biomarkers of oxidative stress (four urinary F2-isoprostane isomers), to estimate oxidative status. Linear regression models were used to evaluate associations between psychosocial stressors, prenatal oxidative status and preterm birth.ResultsAfter adjusting for maternal obesity, gestational diabetes, and cigarette smoking, African American women with higher oxidative status were more likely to report higher maternal adverse childhood experience scores (β = 0.16, se = 1.07, p-value = 0.024) and depression scores (β = 0.05, se = 0.02, p = 0.014). Higher oxidative status was also associated with lower gestational age at birth (β = −0.13, se = 0.06, p = 0.04) in this population. These associations were not apparent in Whites. However, none of the cross-product terms for race/ethnicity and social stressors reached statistical significance (p > 0.05).ConclusionWhile the small sample size limits inference, our novel data suggest that psychosocial stressors may contribute significantly to oxidative stress during pregnancy, and preterm birth or delivery African Americans. If replicated in larger studies, these findings would support oxidative stress reduction using established dietary or pharmacological approaches present a potential avenue to mitigate adverse effects of psychosocial stressors on birth outcomes.}, number={3}, journal={HELIYON}, author={Rose, Deborah K. and Bentley, Loren and Maity, Arnab and Maguire, Rachel L. and Planchart, Antonio and Spasojevic, Ivan and Liu, Andy J. and Thorp Jr, John and Hoyo, Cathrine}, year={2024}, month={Feb} }
 @article{davis_wiegers_wiegers_wyatt_johnson_sciaky_barkalow_strong_planchart_mattingly_2023, title={CTD tetramers: a new online tool that computationally links curated chemicals, genes, phenotypes, and diseases to inform molecular mechanisms for environmental health}, volume={195}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfad069}, abstractNote={Abstract}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Davis, Allan Peter and Wiegers, Thomas C. and Wiegers, Jolene and Wyatt, Brent and Johnson, Robin J. and Sciaky, Daniela and Barkalow, Fern and Strong, Melissa and Planchart, Antonio and Mattingly, Carolyn J.}, year={2023}, month={Sep}, pages={155–168} }
 @article{green_wall_weeks_mattingly_marsden_planchart_2023, title={Developmental cadmium exposure disrupts zebrafish vestibular calcium channels interfering with otolith formation and inner ear function}, volume={96}, ISSN={["1872-9711"]}, DOI={10.1016/j.neuro.2023.04.006}, abstractNote={Dizziness or balance problems are estimated to affect approximately 3.3 million children aged three to 17 years. These disorders develop from a breakdown in the balance control system and can be caused by anything that affects the inner ear or the brain, including exposure to environmental toxicants. One potential environmental toxicant linked to balance disorders is cadmium, an extremely toxic metal that occurs naturally in the earth’s crust and is released as a byproduct of industrial processes. Cadmium is associated with balance and vestibular dysfunction in adults exposed occupationally, but little is known about the developmental effects of low-concentration cadmium exposure. Our findings indicate that zebrafish exposed to 10–60 parts per billion (ppb) cadmium from four hours post-fertilization (hpf) to seven days post-fertilization (dpf) exhibit abnormal behaviors, including pronounced increases in auditory sensitivity and circling behavior, both of which are linked to reductions in otolith growth and are rescued by the addition of calcium to the media. Pharmacological intervention shows that agonist-induced activation of the P2X calcium ion channel in the presence of cadmium restores otolith size. In conclusion, cadmium-induced ototoxicity is linked to vestibular-based behavioral abnormalities and auditory sensitivity following developmental exposure, and calcium ion channel function is associated with these defects.}, journal={NEUROTOXICOLOGY}, author={Green, Adrian J. and Wall, Alex R. and Weeks, Ryan D. and Mattingly, Carolyn J. and Marsden, Kurt C. and Planchart, Antonio}, year={2023}, month={May}, pages={129–139} }
 @article{weeks_banack_howell_thunga_green_cox_planchart_metcalf_2023, title={The Effects of Long-term, Low-dose & beta;-N-methylamino-l-alanine (BMAA) Exposures in Adult SODG93R Transgenic Zebrafish}, volume={8}, ISSN={["1476-3524"]}, DOI={10.1007/s12640-023-00658-z}, journal={NEUROTOXICITY RESEARCH}, author={Weeks, Ryan D. and Banack, Sandra A. and Howell, Shaunacee and Thunga, Preethi and Green, Adrian J. and Cox, Paul A. and Planchart, Antonio and Metcalf, James S.}, year={2023}, month={Aug} }
 @article{weeks_banack_howell_thunga_metcalf_green_cox_planchart_2023, title={The Effects of Long-term, Low-dose beta-N-methylamino-L-alanine (BMAA) Exposures in Adult SODG93R (Aug, 10.1007/s12640-023-00658-z, 2023)}, volume={8}, ISSN={["1476-3524"]}, DOI={10.1007/s12640-023-00664-1}, journal={NEUROTOXICITY RESEARCH}, author={Weeks, Ryan D. and Banack, Sandra A. and Howell, Shaunacee and Thunga, Preethi and Metcalf, James S. and Green, Adrian J. and Cox, Paul A. and Planchart, Antonio}, year={2023}, month={Aug} }
 @article{jima_skaar_planchart_motsinger-reif_cevik_park_cowley_wright_house_liu_et al._2022, title={Genomic map of candidate human imprint control regions: the imprintome}, volume={6}, ISSN={["1559-2308"]}, url={https://doi.org/10.1080/15592294.2022.2091815}, DOI={10.1080/15592294.2022.2091815}, abstractNote={ABSTRACT Imprinted genes – critical for growth, metabolism, and neuronal function – are expressed from one parental allele. Parent-of-origin-dependent CpG methylation regulates this expression at imprint control regions (ICRs). Since ICRs are established before tissue specification, these methylation marks are similar across cell types. Thus, they are attractive for investigating the developmental origins of adult diseases using accessible tissues, but remain unknown. We determined genome-wide candidate ICRs in humans by performing whole-genome bisulphite sequencing (WGBS) of DNA derived from the three germ layers and from gametes. We identified 1,488 hemi-methylated candidate ICRs, including 19 of 25 previously characterized ICRs (https://humanicr.org/). Gamete methylation approached 0% or 100% in 332 ICRs (178 paternally and 154 maternally methylated), supporting parent-of-origin-specific methylation, and 65% were in well-described CTCF-binding or DNaseI hypersensitive regions. This draft of the human imprintome will allow for the systematic determination of the role of early-acquired imprinting dysregulation in the pathogenesis of human diseases and developmental and behavioural disorders.}, journal={EPIGENETICS}, author={Jima, Dereje D. and Skaar, David A. and Planchart, Antonio and Motsinger-Reif, Alison and Cevik, Sebnem E. and Park, Sarah S. and Cowley, Michael and Wright, Fred and House, John and Liu, Andy and et al.}, year={2022}, month={Jun} }
 @article{implementation of zebrafish ontologies for toxicology screening_2022, url={https://www.frontiersin.org/articles/10.3389/ftox.2022.817999/abstract}, DOI={10.3389/ftox.2022.817999}, abstractNote={Toxicological evaluation of chemicals using early-life stage zebrafish (Danio rerio) involves the observation and recording of altered phenotypes. Substantial variability has been observed among researchers in phenotypes reported from similar studies, as well as a lack of consistent data annotation, indicating a need for both terminological and data harmonization. When examined from a data science perspective, many of these apparent differences can be parsed into the same or similar endpoints whose measurements differ only in time, methodology, or nomenclature. Ontological knowledge structures can be leveraged to integrate diverse data sets across terminologies, scales, and modalities. Building on this premise, the National Toxicology Program’s Systematic Evaluation of the Application of Zebrafish in Toxicology undertook a collaborative exercise to evaluate how the application of standardized phenotype terminology improved data consistency. To accomplish this, zebrafish researchers were asked to assess images of zebrafish larvae for morphological malformations in two surveys. In the first survey, researchers were asked to annotate observed malformations using their own terminology. In the second survey, researchers were asked to annotate the images from a list of terms and definitions from the Zebrafish Phenotype Ontology. Analysis of the results suggested that the use of ontology terms increased consistency and decreased ambiguity, but a larger study is needed to confirm. We conclude that utilizing a common data standard will not only reduce the heterogeneity of reported terms but increases agreement and repeatability between different laboratories. Thus, we advocate for the development of a zebrafish phenotype atlas to help laboratories create interoperable, computable data.}, journal={Frontiers in Toxicology}, year={2022} }
 @article{house_hall_park_planchart_money_maguire_huang_mattingly_skaar_tzeng_et al._2019, title={Cadmium exposure and MEG3 methylation differences between Whites and African Americans in the NEST Cohort}, volume={5}, ISSN={2058-5888}, url={http://dx.doi.org/10.1093/eep/dvz014}, DOI={10.1093/eep/dvz014}, abstractNote={Abstract}, number={3}, journal={Environmental Epigenetics}, publisher={Oxford University Press (OUP)}, author={House, John S and Hall, Jonathan and Park, Sarah S and Planchart, Antonio and Money, Eric and Maguire, Rachel L and Huang, Zhiqing and Mattingly, Carolyn J and Skaar, David and Tzeng, Jung Ying and et al.}, editor={Skinner, MikeEditor}, year={2019}, month={Jul} }
 @article{hamm_ceger_allen_stout_maull_baker_zmarowski_padilla_perkins_planchart_et al._2019, title={Characterizing sources of variability in zebrafish embryo screening protocols}, volume={36}, ISSN={1868-596X}, url={http://dx.doi.org/10.14573/altex.1804162}, DOI={10.14573/altex.1804162}, abstractNote={There is a need for fast, efficient, and cost-effective hazard identification and characterization of chemical hazards. This need is generating increased interest in the use of zebrafish embryos as both a screening tool and an alternative to mammalian test methods. A Collaborative Workshop on Aquatic Models and 21st Century Toxicology identified the lack of appropriate and consistent testing protocols as a challenge to the broader application of the zebrafish embryo model. The National Toxicology Program established the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) initiative to address the lack of consistent testing guidelines and identify sources of variability for zebrafish-based assays. This report summarizes initial SEAZIT information-gathering efforts. Investigators in academic, government, and industry laboratories that routinely use zebrafish embryos for chemical toxicity testing were asked about their husbandry practices and standard protocols. Information was collected about protocol components including zebrafish strains, feed, system water, disease surveillance, embryo exposure conditions, and endpoints. Literature was reviewed to assess issues raised by the investigators. Interviews revealed substantial variability across design parameters, data collected, and analysis procedures. The presence of the chorion and renewal of exposure media (static versus static-renewal) were identified as design parameters that could potentially influence study outcomes and should be investigated further with studies to determine chemical uptake from treatment solution into embryos. The information gathered in this effort provides a basis for future SEAZIT activities to promote more consistent practices among researchers using zebrafish embryos for toxicity evaluation.}, number={1}, journal={ALTEX}, publisher={ALTEX Edition}, author={Hamm, Jon and Ceger, Patricia and Allen, David and Stout, Matt and Maull, Elizabeth A. and Baker, Greg and Zmarowski, Amy and Padilla, Stephanie and Perkins, Edward and Planchart, Antonio and et al.}, year={2019}, pages={103–120} }
 @article{kosnik_planchart_marvel_reif_mattingly_2019, title={Integration of curated and high-throughput screening data to elucidate environmental influences on disease pathways}, volume={12}, ISSN={2468-1113}, url={http://dx.doi.org/10.1016/j.comtox.2019.100094}, DOI={10.1016/j.comtox.2019.100094}, abstractNote={Addressing the complex relationship between public health and environmental exposure requires multiple types and sources of data. An important source of chemical data derives from high-throughput screening (HTS) efforts, such as the Tox21/ToxCast program, which aim to identify chemical hazard using primarily in vitro assays to probe toxicity. While most of these assays target specific genes, assessing the disease-relevance of these assays remains challenging. Integration with additional data sets may help to resolve these questions by providing broader context for individual assay results. The Comparative Toxicogenomics Database (CTD), a publicly available database that builds networks of chemical, gene, and disease information from manually curated literature sources, offers a promising solution for contextual integration with HTS data. Here, we tested the value of integrating data across Tox21/ToxCast and CTD by linking elements common to both databases (i.e., assays, genes, and chemicals). Using polymarcine and Parkinson’s disease as a case study, we found that their union significantly increased chemical-gene associations and disease-pathway coverage. Integration also enabled new disease associations to be made with HTS assays, expanding coverage of chemical-gene data associated with diseases. We demonstrate how integration enables development of predictive adverse outcome pathways using 4-nonylphenol, branched as an example. Thus, we demonstrate enhancements to each data source through database integration, including scenarios where HTS data can efficiently probe chemical space that may be understudied in the literature, as well as how CTD can add biological context to those results.}, journal={Computational Toxicology}, publisher={Elsevier BV}, author={Kosnik, Marissa B. and Planchart, Antonio and Marvel, Skylar W. and Reif, David M. and Mattingly, Carolyn J.}, year={2019}, month={Nov}, pages={100094} }
 @article{green_hoyo_mattingly_luo_tzeng_murphy_buchwalter_planchart_2018, title={Cadmium exposure increases the risk of juvenile obesity: a human and zebrafish comparative study}, volume={42}, ISSN={0307-0565 1476-5497}, url={http://dx.doi.org/10.1038/S41366-018-0036-Y}, DOI={10.1038/S41366-018-0036-Y}, abstractNote={Human obesity is a complex metabolic disorder disproportionately affecting people of lower socioeconomic strata, and ethnic minorities, especially African Americans and Hispanics. Although genetic predisposition and a positive energy balance are implicated in obesity, these factors alone do not account for the excess prevalence of obesity in lower socioeconomic populations. Therefore, environmental factors, including exposure to pesticides, heavy metals, and other contaminants, are agents widely suspected to have obesogenic activity, and they also are spatially correlated with lower socioeconomic status. Our study investigates the causal relationship between exposure to the heavy metal, cadmium (Cd), and obesity in a cohort of children and in a zebrafish model of adipogenesis.An extensive collection of first trimester maternal blood samples obtained as part of the Newborn Epigenetics Study (NEST) was analyzed for the presence of Cd, and these results were cross analyzed with the weight-gain trajectory of the children through age 5 years. Next, the role of Cd as a potential obesogen was analyzed in an in vivo zebrafish model.Our analysis indicates that the presence of Cd in maternal blood during pregnancy is associated with increased risk of juvenile obesity in the offspring, independent of other variables, including lead (Pb) and smoking status. Our results are recapitulated in a zebrafish model, in which exposure to Cd at levels approximating those observed in the NEST study is associated with increased adiposity.Our findings identify Cd as a potential human obesogen. Moreover, these observations are recapitulated in a zebrafish model, suggesting that the underlying mechanisms may be evolutionarily conserved, and that zebrafish may be a valuable model for uncovering pathways leading to Cd-mediated obesity in human populations.}, number={7}, journal={International Journal of Obesity}, publisher={Springer Science and Business Media LLC}, author={Green, Adrian J. and Hoyo, Cathrine and Mattingly, Carolyn J. and Luo, Yiwen and Tzeng, Jung-Ying and Murphy, Susan K. and Buchwalter, David B. and Planchart, Antonio}, year={2018}, month={Feb}, pages={1285–1295} }
 @article{planchart_green_hoyo_mattingly_2018, title={Heavy Metal Exposure and Metabolic Syndrome: Evidence from Human and Model System Studies}, volume={5}, ISSN={2196-5412}, url={http://dx.doi.org/10.1007/S40572-018-0182-3}, DOI={10.1007/S40572-018-0182-3}, abstractNote={Metabolic syndrome (MS) describes the co-occurrence of conditions that increase one’s risk for heart disease and other disorders such as diabetes and stroke. The worldwide increase in the prevalence of MS cannot be fully explained by lifestyle factors such as sedentary behavior and caloric intake alone. Environmental exposures, such as heavy metals, have been implicated, but results are conflicting and possible mechanisms remain unclear. To assess recent progress in determining a possible role between heavy metal exposure and MS, we reviewed epidemiological and model system data for cadmium (Cd), lead (Pb), and mercury (Hg) from the last decade. Data from 36 epidemiological studies involving 17 unique countries/regions and 13 studies leveraging model systems are included in this review. Epidemiological and model system studies support a possible association between heavy metal exposure and MS or comorbid conditions; however, results remain conflicting. Epidemiological studies were predominantly cross-sectional and collectively, they highlight a global interest in this question and reveal evidence of differential susceptibility by sex and age to heavy metal exposures. In vivo studies in rats and mice and in vitro cell-based assays provide insights into potential mechanisms of action relevant to MS including altered regulation of lipid and glucose homeostasis, adipogenesis, and oxidative stress. Heavy metal exposure may contribute to MS or comorbid conditions; however, available data are conflicting. Causal inference remains challenging as epidemiological data are largely cross-sectional; and variation in study design, including samples used for heavy metal measurements, age of subjects at which MS outcomes are measured; the scope and treatment of confounding factors; and the population demographics vary widely. Prospective studies, standardization or increased consistency across study designs and reporting, and consideration of molecular mechanisms informed by model system studies are needed to better assess potential causal links between heavy metal exposure and MS.}, number={1}, journal={Current Environmental Health Reports}, publisher={Springer Science and Business Media LLC}, author={Planchart, Antonio and Green, Adrian and Hoyo, Cathrine and Mattingly, Carolyn J.}, year={2018}, month={Feb}, pages={110–124} }
 @article{green_planchart_2018, title={The neurological toxicity of heavy metals: A fish perspective}, volume={208}, ISSN={1532-0456}, url={http://dx.doi.org/10.1016/j.cbpc.2017.11.008}, DOI={10.1016/j.cbpc.2017.11.008}, abstractNote={The causes of neurodegenerative diseases are complex with likely contributions from genetic susceptibility and environmental exposures over an organism's lifetime. In this review, we examine the role that aquatic models, especially zebrafish, have played in the elucidation of mechanisms of heavy metal toxicity and nervous system function over the last decade. Focus is applied to cadmium, lead, and mercury as significant contributors to central nervous system morbidity, and the application of numerous transgenic zebrafish expressing fluorescent reporters in specific neuronal populations or brain regions enabling high-resolution neurodevelopmental and neurotoxicology research.}, journal={Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology}, publisher={Elsevier BV}, author={Green, Adrian J. and Planchart, Antonio}, year={2018}, month={Jun}, pages={12–19} }
 @misc{green_mattingly_planchart_2017, title={Cadmium Disrupts Vestibular Function by Interfering with Otolith Formation}, url={http://dx.doi.org/10.1101/162347}, DOI={10.1101/162347}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Green, Adrian J. and Mattingly, Carolyn J. and Planchart, Antonio}, year={2017}, month={Jul} }
 @article{planchart_mattingly_allen_ceger_casey_hinton_kanungo_kullman_tal_bondesson_et al._2016, title={Advancing toxicology research using in vivo high throughput toxicology with small fish models}, volume={33}, ISSN={1868-596X}, url={http://dx.doi.org/10.14573/altex.1601281}, DOI={10.14573/altex.1601281}, abstractNote={Summary Small freshwater fish models, especially zebrafish, offer advantages over traditional rodent models, including low maintenance and husbandry costs, high fecundity, genetic diversity, physiology similar to that of traditional biomedical models, and reduced animal welfare concerns. The Collaborative Workshop on Aquatic Models and 21st Century Toxicology was held at North Carolina State University on May 5-6, 2014, in Raleigh, North Carolina, USA. Participants discussed the ways in which small fish are being used as models to screen toxicants and understand mechanisms of toxicity. Workshop participants agreed that the lack of standardized protocols is an impediment to broader acceptance of these models, whereas development of standardized protocols, validation, and subsequent regulatory acceptance would facilitate greater usage. Given the advantages and increasing application of small fish models, there was widespread interest in follow-up workshops to review and discuss developments in their use. In this article, we summarize the recommendations formulated by workshop participants to enhance the utility of small fish species in toxicology studies, as well as many of the advances in the field of toxicology that resulted from using small fish species, including advances in developmental toxicology, cardiovascular toxicology, neurotoxicology, and immunotoxicology. We also review many emerging issues that will benefit from using small fish species, especially zebrafish, and new technologies that will enable using these organisms to yield results unprecedented in their information content to better understand how toxicants affect development and health.}, number={4}, journal={ALTEX}, publisher={ALTEX Edition}, author={Planchart, Antonio and Mattingly, Carolyn J. and Allen, David and Ceger, Patricia and Casey, Warren and Hinton, David and Kanungo, Jyotshna and Kullman, Seth W. and Tal, Tamara and Bondesson, Maria and et al.}, year={2016}, pages={435–452} }
 @article{watson_planchart_mattingly_winkler_reif_kullman_2016, title={From the Cover: Embryonic Exposure to TCDD Impacts Osteogenesis of the Axial Skeleton in Japanese medaka,Oryzias latipes}, volume={155}, ISSN={1096-6080 1096-0929}, url={http://dx.doi.org/10.1093/toxsci/kfw229}, DOI={10.1093/toxsci/kfw229}, abstractNote={Recent studies from mammalian, fish, and in vitro models have identified bone and cartilage development as sensitive targets for dioxins and other aryl hydrocarbon receptor ligands. In this study, we assess how embryonic 2,3,7,8-tetrachlorochlorodibenzo-p-dioxin (TCDD) exposure impacts axial osteogenesis in Japanese medaka (Oryzias latipes), a vertebrate model of human bone development. Embryos from inbred wild-type Orange-red Hd-dR and 3 transgenic medaka lines (twist:EGFP, osx/sp7:mCherry, col10a1:nlGFP) were exposed to 0.15 nM and 0.3 nM TCDD and reared until 20 dpf. Individuals were stained for mineralized bone and imaged using confocal microscopy to assess skeletal alterations in medial vertebrae in combination with a qualitative spatial analysis of osteoblast and osteoblast progenitor cell populations. Exposure to TCDD resulted in an overall attenuation of vertebral ossification characterized by truncated centra, and reduced neural and hemal arch lengths. Effects on mineralization were consistent with modifications in cell number and cell localization of transgene-labeled osteoblast and osteoblast progenitor cells. Endogenous expression of osteogenic regulators runt-related transcription factor 2 (runx2) and osterix (osx/sp7), and extracellular matrix genes osteopontin (spp1), collagen type I alpha I (col1), collagen type X alpha I (col10a1), and osteocalcin (bglap/osc) was significantly diminished at 20 dpf following TCDD exposure as compared with controls. Through global transcriptomic analysis more than 590 differentially expressed genes were identified and mapped to select pathological states including inflammatory disease, connective tissue disorders, and skeletal and muscular disorders. Taken together, results from this study suggest that TCDD exposure inhibits axial bone formation through dysregulation of osteoblast differentiation. This approach highlights the advantages and sensitivity of using small fish models to investigate how xenobiotic exposure may impact skeletal development.}, number={2}, journal={Toxicological Sciences}, publisher={Oxford University Press (OUP)}, author={Watson, AtLee T. D. and Planchart, Antonio and Mattingly, Carolyn J. and Winkler, Christoph and Reif, David M. and Kullman, Seth W.}, year={2016}, month={Nov}, pages={485–496} }
 @article{arambula_belcher_planchart_turner_patisaul_2016, title={Impact of Low Dose Oral Exposure to Bisphenol A (BPA) on the Neonatal Rat Hypothalamic and Hippocampal Transcriptome: A CLARITY-BPA Consortium Study}, volume={157}, ISSN={0013-7227 1945-7170}, url={http://dx.doi.org/10.1210/en.2016-1339}, DOI={10.1210/en.2016-1339}, abstractNote={Bisphenol A (BPA) is an endocrine disrupting, high volume production chemical found in a variety of products. Evidence of prenatal exposure has raised concerns that developmental BPA may disrupt sex-specific brain organization and, consequently, induce lasting changes on neurophysiology and behavior. We and others have shown that exposure to BPA at doses below the no-observed-adverse-effect level can disrupt the sex-specific expression of estrogen-responsive genes in the neonatal rat brain including estrogen receptors (ERs). The present studies, conducted as part of the Consortium Linking Academic and Regulatory Insights of BPA Toxicity program, expanded this work by examining the hippocampal and hypothalamic transcriptome on postnatal day 1 with the hypothesis that genes sensitive to estrogen and/or sexually dimorphic in expression would be altered by prenatal BPA exposure. NCTR Sprague-Dawley dams were gavaged from gestational day 6 until parturition with BPA (0-, 2.5-, 25-, 250-, 2500-, or 25 000-μg/kg body weight [bw]/d). Ethinyl estradiol was used as a reference estrogen (0.05- or 0.5-μg/kg bw/d). Postnatal day 1 brains were microdissected and gene expression was assessed with RNA-sequencing (0-, 2.5-, and 2500-μg/kg bw BPA groups only) and/or quantitative real-time PCR (all exposure groups). BPA-related transcriptional changes were mainly confined to the hypothalamus. Consistent with prior observations, BPA induced sex-specific effects on hypothalamic ERα and ERβ (Esr1 and Esr2) expression and hippocampal and hypothalamic oxytocin (Oxt) expression. These data demonstrate prenatal BPA exposure, even at doses below the current no-observed-adverse-effect level, can alter gene expression in the developing brain.}, number={10}, journal={Endocrinology}, publisher={The Endocrine Society}, author={Arambula, Sheryl E. and Belcher, Scott M. and Planchart, Antonio and Turner, Stephen D. and Patisaul, Heather B.}, year={2016}, month={Aug}, pages={3856–3872} }
 @article{schilling_nepomuceno_planchart_yoder_kelly_muddiman_daniels_hiramatsu_reading_2015, title={Machine learning reveals sex-specific 17β-estradiol-responsive expression patterns in white perch (Morone americana
) plasma proteins}, volume={15}, ISSN={1615-9853}, url={http://dx.doi.org/10.1002/pmic.201400606}, DOI={10.1002/pmic.201400606}, abstractNote={With growing abundance and awareness of endocrine disrupting compounds (EDCs) in the environment, there is a need for accurate and reliable detection of EDC exposure. Our objective in the present study was to observe differences within and between the global plasma proteomes of sexually mature male and female white perch (Morone americana) before (Initial Control, IC) and after 17β‐estradiol (E2) induction. Semiquantitative nanoLC‐MS/MS data were analyzed by machine learning support vector machines (SVMs) and by two‐way ANOVA. By ANOVA, the expression levels of 44, 77, and 57 proteins varied significantly by gender, treatment, and the interaction of gender and treatment, respectively. SVMs perfectly classified male and female perch IC and E2‐induced plasma samples using the protein expression data. E2‐induced male and female perch plasma proteomes contained significantly higher levels of the yolk precursors vitellogenin Aa and Ab (VtgAa, VtgAb), as well as latrophilin and seven transmembrane domain‐containing protein 1 (Eltd1) and kininogen 1 (Kng1). This is the first report that Eltd1 and Kng1 may be E2‐responsive proteins in fishes and therefore may be useful indicators of estrogen induction.}, number={15}, journal={PROTEOMICS}, publisher={Wiley}, author={Schilling, Justin and Nepomuceno, Angelito I. and Planchart, Antonio and Yoder, Jeffrey A. and Kelly, Robert M. and Muddiman, David C. and Daniels, Harry V. and Hiramatsu, Naoshi and Reading, Benjamin J.}, year={2015}, month={Jun}, pages={2678–2690} }
 @article{bugel_tanguay_planchart_2014, title={Zebrafish: A Marvel of High-Throughput Biology for 21st Century Toxicology}, volume={1}, ISSN={2196-5412}, url={http://dx.doi.org/10.1007/S40572-014-0029-5}, DOI={10.1007/S40572-014-0029-5}, abstractNote={The evolutionary conservation of genomic, biochemical, and developmental features between zebrafish and humans is gradually coming into focus, with the end result that the zebrafish embryo model has emerged as a powerful tool for uncovering the effects of environmental exposures on a multitude of biological processes with direct relevance to human health. In this review, we highlight advances in automation, high-throughput screening, and analysis that leverage the power of the zebrafish embryo model for unparalleled advances in our understanding of how chemicals in our environment affect our health and wellbeing.}, number={4}, journal={Current Environmental Health Reports}, publisher={Springer Science and Business Media LLC}, author={Bugel, Sean M. and Tanguay, Robert L. and Planchart, Antonio}, year={2014}, month={Sep}, pages={341–352} }
 @article{planchart_2013, title={Analysis of an intronic promoter within Synj2}, volume={440}, ISSN={0006-291X}, url={http://dx.doi.org/10.1016/j.bbrc.2013.09.115}, DOI={10.1016/j.bbrc.2013.09.115}, abstractNote={Synj2 (synaptojanin 2) encodes an inositol polyphosphate phosphatase that functions in recycling neurotransmitter vesicles and is implicated in spermatogenesis. Transcription of Synj2 is thought to occur from one of two promoters based on analysis of a variable 5′ untranslated region. Clustering all known mouse Synj2 transcripts led us to uncover a novel subset of transcripts that appears to derive from a region located within intron 7. We identified two alternate splice variants emanating from use of this promoter. These alternate splice variants manifest developmental stage specificity and somatic versus gametic differences in expression.}, number={4}, journal={Biochemical and Biophysical Research Communications}, publisher={Elsevier BV}, author={Planchart, Antonio}, year={2013}, month={Nov}, pages={640–645} }
 @article{cheng_hinton_mattingly_planchart_2012, title={Aquatic models, genomics and chemical risk management}, volume={155}, ISSN={1532-0456}, url={http://dx.doi.org/10.1016/j.cbpc.2011.06.009}, DOI={10.1016/j.cbpc.2011.06.009}, abstractNote={The 5th Aquatic Animal Models for Human Disease meeting follows four previous meetings (Nairn et al., 2001, Schmale, 2004, Schmale et al., 2007; Hinton et al., 2009) in which advances in aquatic animal models for human disease research were reported, and community discussion of future direction was pursued. At this meeting, discussion at a workshop entitled Bioinformatics and Computational Biology with Web-based Resources (20 September 2010) led to an important conclusion: Aquatic model research using feral and experimental fish, in combination with web-based access to annotated anatomical atlases and toxicological databases, yields data that advance our understanding of human gene function, and can be used to facilitate environmental management and drug development. We propose here that the effects of genes and environment are best appreciated within an anatomical context — the specifically affected cells and organs in the whole animal. We envision the use of automated, whole-animal imaging at cellular resolution and computational morphometry facilitated by high-performance computing and automated entry into toxicological databases, as anchors for genetic and toxicological data, and as connectors between human and model system data. These principles should be applied to both laboratory and feral fish populations, which have been virtually irreplaceable sentinals for environmental contamination that results in human morbidity and mortality. We conclude that automation, database generation, and web-based accessibility, facilitated by genomic/transcriptomic data and high-performance and cloud computing, will potentiate the unique and potentially key roles that aquatic models play in advancing systems biology, drug development, and environmental risk management.}, number={1}, journal={Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology}, publisher={Elsevier BV}, author={Cheng, Keith C. and Hinton, David E. and Mattingly, Carolyn J. and Planchart, Antonio}, year={2012}, month={Jan}, pages={169–173} }
 @article{planchart_mattingly_2010, title={2,3,7,8-Tetrachlorodibenzo-p-dioxin Upregulates FoxQ1b in Zebrafish Jaw Primordium}, volume={23}, ISSN={0893-228X 1520-5010}, url={http://dx.doi.org/10.1021/tx9003165}, DOI={10.1021/tx9003165}, abstractNote={Vertebrate jaw development can be disrupted by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-a potent activator of the aryl hydrocarbon receptor (AHR) transcription factor required for transducing the toxic effects of TCDD. We used zebrafish (Danio rerio) embryos to investigate transcriptional responses to TCDD with the goal of discovering novel, jaw-specific genes affected by TCDD exposure. Our results uncovered a novel target of TCDD-activated Ahr belonging to the evolutionarily conserved family of forkhead box transcription factors. Quantitative real-time polymerase chain reaction analysis demonstrated that FoxQ1b was upregulated by TCDD 7- and 10-fold at 24 and 48 h postfertilization (hpf), respectively. The rate of TCDD-induced FoxQ1b expression was more rapid than that of Cyp1a, a known direct target of TCDD-activated Ahr. TCDD-mediated induction of FoxQ1b was suppressed in the presence of an Ahr antagonist, alpha-naphthoflavone, as well as following knockdown of Ahr2 expression using an Ahr2-specific morpholino antisense oligonucleotide. In situ hybridization analysis of FoxQ1b expression at 48 hpf demonstrated that FoxQ1b is specifically expressed in the jaw primordium where it discretely outlines a developing jaw structure known as Meckel's cartilage--a conserved structure in all jawed vertebrates that develops abnormally in the presence of TCDD. These results identify a novel target of TCDD-activated Ahr and suggest that FoxQ1b may play a role in craniofacial abnormalities induced by developmental exposure to TCDD.}, number={3}, journal={Chemical Research in Toxicology}, publisher={American Chemical Society (ACS)}, author={Planchart, Antonio and Mattingly, Carolyn J.}, year={2010}, month={Mar}, pages={480–487} }
 @article{coffman_coluccio_planchart_robertson_2009, title={Oral-aboral axis specification in the sea urchin embryo. III. Role of mitochondrial redox signaling via H<inf>2</inf>O<inf>2</inf>}, volume={330}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-67349143114&partnerID=MN8TOARS}, DOI={10.1016/j.ydbio.2009.03.017}, abstractNote={In sea urchin embryos, specification of the secondary (oral–aboral) axis occurs via nodal, expression of which is entirely zygotic and localized to prospective oral ectoderm at blastula stage. The initial source of this spatial anisotropy is not known. Previous studies have shown that oral–aboral (OA) polarity correlates with a mitochondrial gradient, and that nodal activity is dependent both on mitochondrial respiration and p38 stress-activated protein kinase. Here we show that the spatial pattern of nodal activity also correlates with the mitochondrial gradient, and that the latter correlates with inhomogeneous levels of intracellular reactive oxygen species. To test whether mitochondrial H2O2 functions as a redox signal to activate nodal, zygotes were injected with mRNA encoding either mitochondrially-targeted catalase, which quenches mitochondrial H2O2 and down-regulates p38, or superoxide dismutase, which augments mitochondrial H2O2 and up-regulates p38. Whereas the former treatment inhibits the initial activation of nodal and entrains OA polarity toward aboral when confined to half of the embryo via 2-cell stage blastomere injections, the latter does not produce the opposite effects. We conclude that mitochondrial H2O2 is rate-limiting for the initial activation of nodal, but that additional rate-limiting factors, likely also involving mitochondria, contribute to the asymmetry in nodal expression.}, number={1}, journal={Developmental Biology}, author={Coffman, J.A. and Coluccio, A. and Planchart, A. and Robertson, A.J.}, year={2009}, pages={123–130} }
 @article{mattingly_hampton_brothers_griffin_planchart_2009, title={Perturbation of Defense Pathways by Low-Dose Arsenic Exposure in Zebrafish Embryos}, volume={117}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.0900555}, DOI={10.1289/ehp.0900555}, abstractNote={Background Exposure to arsenic is a critical risk factor in the complex interplay among genetics, the environment, and human disease. Despite the potential for in utero exposure, the mechanism of arsenic action on vertebrate development and disease is unknown. Objectives The objective of this study was to identify genes and gene networks perturbed by arsenic during development in order to enhance understanding of the molecular mechanisms of arsenic action. Methods We exposed zebrafish embryos at 0.25–1.25 hr postfertilization to 10 or 100 ppb arsenic for 24 or 48 hr. We then used total RNA to interrogate genome microarrays and to test levels of gene expression changes by quantitative real-time polymerase chain reaction (QPCR). Computational analysis was used to identify gene expression networks perturbed by arsenic during vertebrate development. Results We identified a set of 99 genes that responded to low levels of arsenic. Nineteen of these genes were predicted to function in a common regulatory network that was significantly associated with immune response and cancer (p < 10−41). Arsenic-mediated expression changes were validated by QPCR. Conclusions In this study we demonstrated that arsenic significantly down-regulates expression levels of multiple genes potentially critical for regulating the establishment of an immune response. The data also provide molecular evidence consistent with phenotypic observations reported in other model systems. Additional mechanistic studies will help explain molecular events regulating early stages of the immune system and long-term consequences of arsenic-mediated perturbation of this system during development.}, number={6}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Mattingly, Carolyn J. and Hampton, Thomas H. and Brothers, Kimberly M. and Griffin, Nina E. and Planchart, Antonio}, year={2009}, month={Jun}, pages={981–987} }
 @article{schlax_zhang_lewis_planchart_lawson_2007, title={Degradation of the encephalomyocarditis virus and hepatitis A virus 3C proteases by the ubiquitin/26S proteasome system in vivo}, volume={360}, ISSN={0042-6822}, url={http://dx.doi.org/10.1016/j.virol.2006.10.043}, DOI={10.1016/j.virol.2006.10.043}, abstractNote={We have isolated stably transfected mouse embryonic fibroblast cell lines that inducibly express either the mature encephalomyocarditis virus (EMCV) or hepatitis A virus (HAV) 3C protease and have used these cells to demonstrate that both proteins are subject to degradation in vivo by the ubiquitin/26S proteasome system. The detection of 3C protease expression in these cells requires inducing conditions and the presence of one of several proteasome inhibitors. Both 3C proteases are incorporated into conjugates with ubiquitin in vivo. HAV 3C protease expression has deleterious effects on cell viability, as determined by observation and counting of cells cultured in the absence or presence of inducing conditions. The EMCV 3C protease was found to be preferentially localized to the nucleus of induced cells, while the HAV 3C protease remains in the cytoplasm. The absence of polyubiquitinated EMCV 3C protease conjugates in nuclear fraction preparations suggests that localization to the nucleus can protect this protein from ubiquitination.}, number={2}, journal={Virology}, publisher={Elsevier BV}, author={Schlax, Peter E. and Zhang, Jin and Lewis, Elizabeth and Planchart, Antonio and Lawson, T. Glen}, year={2007}, month={Apr}, pages={350–363} }
 @article{schimenti_reynolds_planchart_2005, title={Mutations in Serac1 or Synj2 cause proximal t haplotype-mediated male mouse sterility but not transmission ratio distortion}, volume={102}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.0407970102}, DOI={10.1073/pnas.0407970102}, abstractNote={
            Transmission ratio distortion (TRD) and sterility are male-specific quantitative trait phenomena associated with the mouse
            t
            haplotype. TRD occurs in
            t
            haplotype-heterozygous males and is caused by the deleterious action of distorter products on sperm bearing a wild-type responder locus. It has been proposed that
            t
            -mediated male sterility is a severe manifestation of TRD caused by homozygosity for distorter loci; thus, the distorter and sterility loci would be identical. In this, study a transgenic approach was used to identify the proximal sterility locus,
            tcs1
            (S1), and test its role in TRD. Mice transgenic for a wild-type bacterial artificial chromosome (BAC) derived from the S1-critical region were bred onto
            t
            haplotype backgrounds. Mating results conclusively showed that the BAC is sufficient to restore fertility in otherwise sterile males. Multiple mutations were identified in the
            t
            alleles of
            Synj2
            and
            Serac1
            , two genes in the BAC; thus, they are candidates for S1. In addition, whereas the BAC transgene rescued sterility, it had no effect on TRD. These results uncouple the proximal
            t
            haplotype sterility locus, S1, from TRD, demonstrating that S1 and the proximal distorter locus, D1, are not the same gene.
          }, number={9}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Schimenti, J. C. and Reynolds, J. L. and Planchart, A.}, year={2005}, month={Feb}, pages={3342–3347} }
 @article{blake_richardson_bult_kadin_eppig_baldarelli_beal_bradt_burkart_butler_et al._2003, title={MGD: the Mouse Genome Database}, volume={31}, ISSN={1362-4962}, url={http://dx.doi.org/10.1093/nar/gkg047}, DOI={10.1093/nar/gkg047}, abstractNote={The Mouse Genome Database (MGD) (http://www.informatics.jax.org) one component of a community database resource for the laboratory mouse, a key model organism for interpreting the human genome and for understanding human biology. MGD strives to provide an extensively integrated information resource with experimental details annotated from both literature and on-line genomic data sources. MGD curates and presents the consensus representation of genotype (sequence) to phenotype information including highly detailed information about genes and gene products. Primary foci of integration are through representations of relationships between genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse. Recent developments include a general implementation of database structures for controlled vocabularies and the integration of a phenotype classification system.}, number={1}, journal={Nucleic Acids Research}, publisher={Oxford University Press (OUP)}, author={Blake, J.A. and Richardson, J.E. and Bult, C.J. and Kadin, J.A. and Eppig, J.T. and Baldarelli, R.M. and Beal, J.S. and Bradt, D.W. and Burkart, D.L. and Butler, N.E. and et al.}, year={2003}, month={Jan}, pages={193–195} }
 @article{blake_richardson_bult_kadin_eppig_baldarelli_baya_beal_boddy_bradt_et al._2002, title={The Mouse Genome Database (MGD): the model organism database for the laboratory mouse}, volume={30}, ISSN={1362-4962}, url={http://dx.doi.org/10.1093/nar/30.1.113}, DOI={10.1093/nar/30.1.113}, abstractNote={The Mouse Genome Database (MGD) is the community database resource for the laboratory mouse, a key model organism for interpreting the human genome and for understanding human biology and disease (http://www.informatics.jax.org). MGD strives to provide a highly curated, highly integrated information resource that not only includes the consensus view of current knowledge about the mouse, but also provides comparative genomic information particularly for human and rat genomes. MGD includes extensive information about mouse genes, supporting all gene attribute assertions with experimental data, statements of evidence and citation. Detailed information about alleles and mouse mutants includes genotype, molecular variant and phenotype descriptions. Extensive collaboration with other data providers such as NCBI, RIKEN and SWISS-PROT provides standardization of gene:sequence associations and robust interconnections between large information systems based on shared sequence curation. Recent integration of large datasets of mouse full-length cDNAs and radiation-hybrid mapped ESTs, the continued development and use of extensive structured vocabularies and the expansion of the representation of phenotypes highlight this year's developments.}, number={1}, journal={Nucleic Acids Research}, publisher={Oxford University Press (OUP)}, author={Blake, J. A. and Richardson, J.E. and Bult, C.J. and Kadin, J.A. and Eppig, J.T. and Baldarelli, R. M. and Baya, M. and Beal, J. S. and Boddy, W. J. and Bradt, D. W. and et al.}, year={2002}, month={Jan}, pages={113–115} }
 @article{planchart_schimenti_2001, title={Experimental and computational approaches yield a high-resolution, 1-Mb physical map of the region harboring the mouse t haplotype sterility factor, tcs1}, volume={12}, ISSN={0938-8990 1432-1777}, url={http://dx.doi.org/10.1007/s00335-001-1002-9}, DOI={10.1007/s00335-001-1002-9}, number={8}, journal={Mammalian Genome}, publisher={Springer Science and Business Media LLC}, author={Planchart, Antonio and Schimenti, John C.}, year={2001}, month={Aug}, pages={668–670} }
 @article{browning_chaudhry_planchart_dixon_schimenti_2001, title={Mutations of the Mouse Twist and sy (Fibrillin 2) Genes Induced by Chemical Mutagenesis of ES Cells}, volume={73}, ISSN={0888-7543}, url={http://dx.doi.org/10.1006/geno.2001.6523}, DOI={10.1006/geno.2001.6523}, abstractNote={A prior phenotype-based screen of mice derived from ethylmethanesulfonate-mutagenized embryonic stem cells yielded two mouse limb defect mutants. Animals heterozygous for the polydactyly ems (Pde) mutation display preaxial polydactyly of the hindlimbs, and homozygous syndactyly ems (sne) animals are characterized by a fusion of the middle digits of their hindlimbs and sometimes forelimbs. We now report that Pde is a new allele of the basic helix-loop-helix protein gene Twist. Sequencing the full-length cDNA and several hundred basepairs of genomic DNA upstream of the coding region failed to reveal a mutation, suggesting that the lesion may be in a regulatory element of the gene. sne is a new fused phalanges (fp) allele of the shaker-with-syndactylism deletion complex (sy), and we show that the genomic lesion is a small deletion removing an entire exon, coincident with the insertion of the 3' end of a LINE element belonging to the TF subfamily.}, number={3}, journal={Genomics}, publisher={Elsevier BV}, author={Browning, Victoria L. and Chaudhry, Shazia S. and Planchart, Antonio and Dixon, Michael J. and Schimenti, John C.}, year={2001}, month={May}, pages={291–298} }
 @article{planchart_you_schimenti_2000, title={Physical mapping of male fertility and meiotic drive quantitative trait loci in the mouse t complex using chromosome deficiencies}, volume={155}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034084813&partnerID=MN8TOARS}, number={2}, journal={Genetics}, author={Planchart, A. and You, Y. and Schimenti, J.C.}, year={2000}, pages={803–812} }
 @article{wang_planchart_stubbs_1998, title={Caspar Carboxylates: The Structural Basis of Tobamovirus Disassembly}, volume={74}, ISSN={0006-3495}, url={http://dx.doi.org/10.1016/S0006-3495(98)77822-1}, DOI={10.1016/S0006-3495(98)77822-1}, abstractNote={Carboxylate groups have been known for many years to drive the disassembly of simple viruses, including tobacco mosaic virus (TMV). The identities of the carboxylate groups involved and the mechanism by which they initiate disassembly have not, however, been clear. Structures have been determined at resolutions between 2.9 and 3.5 A for five tobamoviruses by fiber diffraction methods. Site-directed mutagenesis has also been used to change numerous carboxylate side chains in TMV to the corresponding amides. Comparison of the stabilities of the various mutant viruses shows that disassembly is driven by a much more complex set of carboxylate interactions than had previously been postulated. Despite the importance of the carboxylate interactions, they are not conserved during viral evolution. Instead, it appears that during evolution, patches of electrostatic interaction drift across viral subunit interfaces. The flexibility of these interactions confers a considerable advantage on the virus, enabling it to change its surface structure rapidly and thus evade host defenses.}, number={1}, journal={Biophysical Journal}, publisher={Elsevier BV}, author={Wang, Hong and Planchart, Antonio and Stubbs, Gerald}, year={1998}, month={Jan}, pages={633–638} }
 @article{wang_planchart_allen_pattanayek_stubbs_1993, title={Preliminary X-ray Diffraction Studies of Ribgrass Mosaic Virus}, volume={234}, ISSN={0022-2836}, url={http://dx.doi.org/10.1006/jmbi.1993.1639}, DOI={10.1006/jmbi.1993.1639}, abstractNote={Fiber diffraction data were collected from oriented sols of ribgrass mosaic virus and a lead derivative of the virus. Two lead binding sites were found. Two intersubunit carboxylcarboxylate pairs, different from those in other tobamoviruses, are predicted to control viral assembly and disassembly. One of the carboxyl-carboxylate pairs forms part of a lead binding site.}, number={3}, journal={Journal of Molecular Biology}, publisher={Elsevier BV}, author={Wang, Hong and Planchart, Antonio and Allen, Diane and Pattanayek, Rekha and Stubbs, Gerald}, year={1993}, month={Dec}, pages={902–904} }
 @article{characterization of a novel dna motif in the tctex1 and tcp10 gene complexes and its prevalence in the mouse genome., journal={Advances in Biological Research (Rennes)} }