Seth W Kullman's research while affiliated with North Carolina State University and other places

Publications (109)

Article
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Alkylphenol polyethoxylates (APEOs), such as nonylphenol ethoxylates (NPEOs), are high-production-volume surfactants used in laundry detergents, hard-surface cleaners, pesticide formulations, textile production, oils, paints, and other products. NPEOs comprise −80% of the total production of APEOs and are widely reported across diverse environmenta...
Article
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Vitamin D is well known for its traditional role in bone mineral homeostasis; however, recent evidence suggests that vitamin D also plays a significant role in metabolic control. This study served to investigate putative linkages between vitamin D deficiency (VDD) and metabolic disruption of bioactive lipids by mass spectrometry imaging (MSI). Our...
Article
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Research suggests that thyroid cancer incidence rates are increasing, and environmental exposures have been postulated to be playing a role. To explore this possibility, we conducted a pilot study to investigate the thyroid disrupting bioactivity of chemical mixtures isolated from personal silicone wristband samplers within a thyroid cancer cohort....
Article
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Vitamin D de ciency (VDD) is a widespread nutrient de ciency characterized by serum 25,hydroxyvitamin D (25(OH)D) levels below 20 ng/mL 1,2. Globally, VDD impacts roughly one billion individuals as a result of dietary depletion, insu cient sunlight exposure, or genetic variants 1. In recent years, the vitamin D/VDR (vitamin D receptor) signaling ax...
Article
The 20th Pollutant Responses in Marine Organisms (PRIMO 20) conference provided a forum for scientists from around the world to communicate novel toxicological research findings specifically focused on aquatic organisms, by combining applied and basic research at the intersection of environmental and mechanistic toxicology. The work highlighted in...
Article
Vitamin D receptor (VDR) signaling is important for optimal neurobehavioral development. Disruption of VDR signaling by environmental toxicants during early development might contribute to the etiology of behavioral dysfunction. In the current set of studies, we examined ten compounds known to affect VDR function in vitro for neurobehavioral effect...
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The zebrafish (Danio rerio) is an ideal model for whole animal studies of lipid metabolism and lipid-related disease. In this work, infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) was applied for direct visualization of lipid and metabolite distributions across various organs in whole-b...
Article
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Vitamin D is an essential nutrient that is metabolized in the body to generate an active metabolite (1,25(OH)2D) with hormone-like activity and highly diverse roles in cellular function. Vitamin D deficiency (VDD) is a prevalent but easily preventable nutritional disturbance. Emerging evidence demonstrates the importance of sufficient vitamin D con...
Article
Multipotent mesenchymal stem cells maintain the ability to differentiate into adipogenic, chondrogenic, or osteogenic cell lineages. There is increasing concern that exposure to environmental agents such as aryl hydrocarbon receptor (AhR) ligands, may perturb the osteogenic pathways responsible for normal bone formation. The objective of the curren...
Article
Endocrine active compounds (EACs) are pollutants that have been recognized as an emerging and widespread threat to aquatic ecosystems globally. Intersex, the presence of female germ cells within a predominantly male gonad, is considered a biomarker of endocrine disruption caused by EACs. We measured a suite of EACs and assessed their associated imp...
Article
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High throughput screening (HTS) programs have demonstrated that the Vitamin D receptor (VDR) is activated and/or antagonized by a wide range of structurally diverse chemicals. In this study, we examined the Tox21 qHTS data set generated against VDR for reproducibility and concordance and elucidated functional insights into VDR-xenobiotic interactio...
Article
A facility-wide estrogen budget model was developed to assess the excretion of natural estrogens by swine in a commercial swine farrowing concentrated animal feeding operations (CAFO) in North Carolina, using an object-oriented Bayesian network (OOBN) approach. The OOBN model is the combination of twelve objects of Bayesian network models, which ch...
Article
Background/Objective Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. Additionally, little is known about how vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring. Subject...
Article
Estrogens and estrogen mimics are commonly found in surface waters and are associated with deleterious effects in fish populations. Impaired fertility and fecundity in fish following chronic exposures to estrogens and estrogen mimics during critical windows in development are well documented. However, information regarding differential reproductive...
Data
Sequence homology of the retinoid X receptor (RXR). The numbers in each table represent the percent sequence identity conserved between the two species. The full-length receptor is depicted in (A). The ligand binding domain is depicted in (B) and the DNA binding domain is depicted in (C). Sequences were identified through BLAST analysis and aligned...
Article
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The evolution, molecular behavior, and physiological function of nuclear receptors are of particular interest given their diverse roles in regulating essential biological processes. The vitamin D receptor (VDR) is well known for its canonical roles in calcium homeostasis and skeletal maintenance. Additionally, VDR has received an increased amount o...
Data
Sequence alignment of NR boxes of SRC1 and GRIP1. (A) Depicts the conserved sequence motif of the SRC/p160 NR boxes: L represents leucine, and X can be any amino acid. (B) And (C) depict the sequence alignments of the three NR boxes for SRC1 (B) and GRIP1 (C). Sequence conservation is indicated by symbols at the bottom of the alignments as well as...
Article
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Worldwide concern about the impacts of endocrine disrupting compounds on both human and environmental health has led to implementation of multiple screening and testing programs. In most cases these programs have focused on impacts to the estrogen, androgen and thyroid hormone (EAT) signaling pathways. The goal of the presentations in session five...
Article
Full-text available
Worldwide concern about the impacts of endocrine disrupting compounds on both human and environmental health has led to implementation of multiple screening and testing programs. In most cases these programs have focused on impacts to the estrogen, androgen and thyroid hormone (EAT) signaling pathways. The goal of the presentations in session five...
Article
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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 vert...
Article
Male fish are susceptible to developing intersex, a condition characterized by the presence of testicular oocytes. In the present study, the relationship between intersex and exposure to estrogenic endocrine active contaminants (EACs) was assessed for 2 genera of sport fish, Micropterus and Lepomis, at 20 riverine sites. Seasonal trends and relatio...
Article
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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 21 st Century Toxicol...
Article
Polybrominated diphenyl ethers (PBDEs) and their metabolites (e.g. hydroxylated BDEs (OH-BDEs)) are contaminants detected together frequently in human tissues, and are structurally similar to thyroid hormones (TH). THs partially mediate metamorphic transitions between life stages in zebrafish, making this a critical developmental window which may b...
Article
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Animal feeding operations (AFOs) have been implicated as potentially major sources of estrogenic contaminants into the aquatic environment due to the relatively minimal treatment of waste and potential mobilization and transport of waste components from spray fields. In this study a Bayesian network (BN) model was developed to inform management dec...
Article
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The vertebrate genome is a result of two rapid and successive rounds of whole genome duplication, referred to as 1R and 2R. Furthermore, teleost fish have undergone a third whole genome duplication (3R) specific to their lineage, resulting in the retention of multiple gene paralogs. The more recent 3R event in teleosts provides a unique opportunity...
Article
The presence of endocrine disrupting compounds (EDCs), particularly estrogenic compounds, in the environment has drawn public attention across the globe, yet we currently lack a clear understanding of the extent and distribution of estrogenic EDCs in surface waters and their relationship to potential sources. The objective of our study was to ident...
Article
The diversity and success of teleost fishes (Actinopterygii) has been attributed to three successive rounds of whole genome duplication (WGD). WGDs provide a source of raw genetic material for evolutionary forces to act upon, resulting in the divergence of genes with altered or novel functions. The retention of multiple gene pairs (paralogs) in tel...
Article
Commercial swine waste lagoons are regarded as a major reservoir of natural estrogens, which have the potential to produce adverse physiological effects on exposed aquatic organisms and wildlife. However, there remains limited understanding of the complex mechanisms of physical, chemical, and biological processes that govern the fate and transport...
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The inflow, transformation, and attenuation of natural steroid hormones, phytoestrogens, and estrogenic activity was assessed across the lagoon/sprayfield system of a prototypical commercial swine sow operation. Free and conjugated steroid hormones (estrogens, androgens, and progesterone) were detected in urine and feces of sows across reproductive...
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This study seeks to delineate the ligand interactions that drive biomarker induction in fish exposed to estrogenic pollutants, and provide a case study on the capacity of human (h) estrogen receptor (ER)-based in vitro screening assays to predict estrogenic effects in aquatic species. Adult male Japanese medaka (Oryzias latipes) were exposed to sol...
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In this study, the distribution of steroid hormones, phytoestrogens, and estrogenic activity was thoroughly characterized within the anaerobic waste lagoon of a typical commercial swine sow operation. Three independent rounds of sampling were conducted in June 2009, April 2010, and February 2011. Thirty-seven analytes in lagoon slurry and sludge we...
Article
Transgenic organisms that express fluorescent proteins are used frequently for in vivo visualization of proteins and cells. The phenotype of a transgenic medaka (Oryzias latipes) strain that expresses a red fluorescent protein (RFP) in hepatocytes was characterized using light and fluorescence microscopy, immunohistochemistry, and transmission elec...
Article
Laboratory fish species are used increasingly in biomedical research and are considered robust models for the study of regenerative processes. Studies investigating the response of the fish liver to injury have demonstrated the presence of a ductular reaction and oval-like cells in injured and regenerating liver. To date, however, it is unclear if...
Article
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Environmental estrogens are ubiquitous in the environment and can cause detrimental effects on male reproduction. In fish, a multitude of effects from environmental estrogens have been observed including altered courting behavior and fertility, sex reversal, and gonadal histopathology. However, few studies in fish assess the impacts of estrogenic e...
Article
Fish have been used as laboratory models to study hepatic development and carcinogenesis but not for pathogenesis of hepatic fibrosis. In this study, a dimethylnitrosamine-induced fish model of hepatic injury was developed in Japanese medaka (Oryzias latipes) and gene expression was anchored with the development of hepatic fibrosis and neoplasia. E...
Conference Paper
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The presence of endocrine disrupting compounds (EDCs), particularly estrogens and estrogen mimics, has drawn public concern across the globe. Evidence linking EDCs with fish reproductive impairment (e.g., feminized males) indicate that waters impacted by EDCs may lead to fish population declines. However, one of the many troubling aspects of EDCs i...
Article
The availability of multiple teleost (bony fish) genomes is providing unprecedented opportunities to understand the diversity and function of gene duplication events using comparative genomics. Here we examine multiple paralogous genes of γ-glutamyl transferase (GGT) in several distantly related teleost species including medaka, stickleback, green...
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Defective bone and cartilage development account for a large number of human birth defects annually. Normal skeletogenesis involves cartilage development in early morphogenesis through a highly coordinated and orchestrated series of events involving commitment and differentiation of mesenchymal cells to chondrocytes followed by a highly programmed...
Technical Report
Increasing incidents of disorders such as obesity/diabetes/metabolic syndrome, reproductive dysfunction, and neuro-developmental abnormalities in some human populations have raised concern that disruption of key endocrine-signaling pathways by exposure to environmental chemicals may be involved. This Detailed Review Paper describes some endocrine p...
Article
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The farnesoid X receptor (FXR), pregnane X receptor (PXR), and vitamin D receptor (VDR) are three closely related nuclear hormone receptors in the NR1H and 1I subfamilies that share the property of being activated by bile salts. Bile salts vary significantly in structure across vertebrate species, suggesting that receptors binding these molecules m...
Data
Activation data for VDRs, including the site-directed mutants of mouse VDR.
Data
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Fish phylogeny, bile salt variation, and nuclear hormone receptor ligand specificity.
Article
Background The farnesoid X receptor (FXR), pregnane X receptor (PXR), and vitamin D receptor (VDR) are three closely related nuclear hormone receptors in the NR1H and 1I subfamilies that share the property of being activated by bile salts. Bile salts vary significantly in structure across vertebrate species, suggesting that receptors binding these...
Data
Activation data for Tetraodon FXR and PXR by bile salts, steroids, and synthetic ligands.
Data
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Data for pharmacophore modeling of Tetraodon nuclear hormone receptors.
Data
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Amino acid sequence alignment for VDRs (including the four chimeric constructs involving the H1-H3 insertion domain) and human PXR.
Data
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Analyses of biliary bile salts from the green-spotted pufferfish.
Data
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The ligand binding pocket of human VDR. Surface representation of human VDR ligand binding pocket.
Article
Animal waste-borne steroidal hormones, which are referred to as natural steroidal estrogens, are recognized pollutants to surface water systems. Steroidal estrogens exhibit strong potency, even at very low concentrations, as endocrine disrupting chemicals on aquatic organisms. In North Carolina, the swine concentrated animal feeding operations (CAF...
Article
Exposure to dioxin and other aryl hydrocarbon receptor (AhR) ligands results in multiple, specific developmental cardiovascular phenotypes including pericardial edema and circulatory failure in small aquarium fish models. Although phenotypes are well described, mechanistic underpinnings for such toxicities remain elusive. Here we suggest that AhR a...
Article
The nuclear receptor farnesoid X receptor alpha (FXRalpha, NR1H4) is activated by bile acids in multiple species including mouse, rat, and human and in this study we have identified two isoforms of Fxralpha in Japanese medaka (Oryzias latipes), a small freshwater teleost. Both isoforms share a high amino acid sequence identity to mammalian FXRalpha...
Article
The small freshwater teleost, medaka (Oryzias latipes), has a history of usage in studies of chronic toxicity of liver and biliary system. Recent progress with this model has focused on defining the medaka hepatobiliary system. Here we investigate critical liver function and toxicity by examining the in vivo role and function of the farnesoid X rec...
Article
Small aquarium fishes are increasingly used as animal models, and one of these, the Japanese Medaka (Oryzias latipes), is frequently utilized for toxicity testing. While these vertebrates have many similarities with their terrestrial counterparts, there are differences that must be considered if these organisms are to be used to their highest poten...
Article
Polycyclic aromatic hydrocarbons (PAHs) are widespread persistent pollutants that readily undergo biotic and abiotic conversion to numerous transformation products in rivers, lakes and estuarine sediments. Here we characterize the developmental toxicity of four PAH transformation products each structural isomers of hydroxynaphthoic acid: 1H2NA, 2H1...
Data
In vivo confocal imaging of hepatobiliary system, STII medaka, 9 dpf. Example of a confocal stack acquired in vivo. Parenchyma elucidated here with β-Bodipy C5 ceramide. Hepatocyte nuclei (HN) appear dark (non fluorescent), cytosol is distinct. Red blood cells can be seen in circulation through sinusoids (S/r). Note differential fluorescence betwee...
Data
Example of 3D projection of parenchyma from in vivo confocal image stacks: STII medaka, 12 dpf. 3D projections of confocal image stacks, in conjunction with 3D reconstructions, aided in evaluation of 3D hepatobiliary architecture. Intrahepatic biliary passageways (IHBPs) of the liver, denoted by increased fluorescence, elucidated with β-Bodipy C5 P...
Data
Example of 3D reconstruction of hepatobiliary architecture from in vivo confocal image stack: sinusoids and parenchymal architecture, STII medaka, 30 dpf. Sinusoids (S) are red. All space between sinusoids (empty) is hepatocellular space, not rendered for visual clarity. Morphometric and volumetric analyses of 3D reconstructions allowed elucidation...
Data
Three-dimensional reconstruction of canaliculi and sinusoids from in vivo confocal image stack: relationship of sinusoids to intrahepatic biliary passageways, STII medaka, 30 dpf. Shown is an isolated section of the parenchyma from a 3D reconstruction. Canaliculi (C, green), which average 1.3 μm in diameter, are green, sinusoids (S, red). Examples...
Data
Example of 3D reconstruction of hepatic parenchyma from in vivo confocal image stack: bile preductules and preductular epithelial cells, STII medaka, 24 dpf. Shown is an isolated section of the parenchyma showing the 3D characteristics of bile preductular epithelia (BPDEC) and bile preductules (BPD), the latter a unique morphological feature create...
Data
Example of 3D reconstruction of parenchyma from in vivo confocal image stacks: relationship of sinusoids to intrahepatic biliary passageways, STII medaka, 30 dpf. Sinusoids (S) are red, canaliculi (C) in green. All space between sinusoids and surrounding canaliculi (empty) is hepatocellular space, not rendered for visual clarity. Morphometric and v...
Data
Example of 3D projection of liver and gall bladder from in vivo confocal image stacks: STII medaka, 12 dpf. 3D projections of confocal image stacks, in conjunction with 3D reconstructions, aided in evaluation of 3D architecture of the hepatobiliary system. Intrahepatic biliary passageways (IHBPs) of the liver (L), and gall bladder (GB) were elucida...
Data
Example of 3D reconstruction of the hepatobiliary system from in vivo confocal image stacks: relationship of sinusoids to intrahepatic biliary passageways, STII medaka, 12 dpf. Sinusoids (S) are denoted in red, intrahepatic biliary passageways (IHBPs) in green/gold. All space between sinusoids and surrounding IHBPs is hepatocellular space, not rend...
Data
STII medaka, 12 dpf, left lateral view. Lacking dermal and visceral pigmentation, internal organs are readily visible through the body wall, and amenable to in vivo observation/imaging. Note peristalsis in the gut on a temporal scale. Liver (L), Gut (Gt), Otic Vesicle (Ov), Spleen (Sp), Air/Swim Bladder (AB), Heart (H).