Drinking water sources, quality, and associated health outcomes in Appalachian Virginia: A risk characterization study in two counties.

Objectives: In the US, violations of drinking water regulations are highest in lower-income rural areas overall, and particularly in Central Appalachia. However, data on drinking water use, quality, and associated health outcomes in rural Appalachia are limited. We sought to assess public and private drinking water sources and associated risk factors for waterborne pathogen exposures for individuals living in rural regions of Appalachian Virginia.

High-throughput AR dimerization assay identifies androgen disrupting chemicals and metabolites.

Analysis of streamlined computational models used to predict androgen disrupting chemicals revealed that assays measuring androgen receptor (AR) cofactor recruitment/dimerization were particularly indispensable to high predictivity, especially for AR antagonists. As the original dimerization assays used to develop the minimal assay models are no longer available, new assays must be established and evaluated as suitable alternatives to assess chemicals beyond the original 1,800+ supported by the current data. Here we present the AR2 assay, which is a stable, cell-based method that uses an enzyme complementation approach.

A Multiplex Noninvasive Salivary Antibody Assay for SARS-CoV-2 Infection and Its Application in a Population-Based Survey by Mail.

Noninvasive salivary antibody immunoassays can enable low-cost epidemiological surveillance of infections. This study involved developing and validating a multiplex suspension immunoassay on the Luminex platform to measure immunoglobulin G (IgG) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid and spike (S) proteins, and the spike protein's S1 and S2 subunits and receptor binding domain. Multiple versions of these recombinant proteins acquired from commercial and noncommercial sources were evaluated.

Expanded high-throughput screening and chemotype-enrichment analysis of the phase II: e1k ToxCast library for human sodium-iodide symporter (NIS) inhibition.

The sodium-iodide symporter (NIS) mediates the uptake of iodide into the thyroid. Inhibition of NIS function by xenobiotics has been demonstrated to suppress circulating thyroid hormones and perturb related physiological functions. Until recently, few environmental chemicals had been screened for NIS inhibition activity.

Respirometric Screening and Characterization of Mitochondrial Toxicants Within the ToxCast Phase I and II Chemical Libraries.

Mitochondrial toxicity drives several adverse health outcomes. Current high-throughput screening assays for chemically induced mitochondrial toxicity typically measure changes to mitochondrial structure and may not detect known mitochondrial toxicants. We adapted a respirometric screening assay (RSA) measuring mitochondrial function to screen ToxCast chemicals in HepG2 cells using a tiered testing strategy.

High-throughput screening and chemotype-enrichment analysis of ToxCast phase II chemicals evaluated for human sodium-iodide symporter (NIS) inhibition.

In support of the Endocrine Disruptor Screening Program (EDSP), the U.S.EPA's Office of Research and Development (ORD) is developing high-throughput screening (HTS) approaches to identify chemicals that alter target sites in the thyroid hormone (TH) pathway.

High-Throughput Screening and Quantitative Chemical Ranking for Sodium-Iodide Symporter Inhibitors in ToxCast Phase I Chemical Library.

Thyroid uptake of iodide via the sodium-iodide symporter (NIS) is the first step in the biosynthesis of thyroid hormones that are critical for health and development in humans and wildlife. Despite having long been a known target of endocrine disrupting chemicals such as perchlorate, information regarding NIS inhibition activity is still unavailable for the vast majority of environmental chemicals. This study applied a previously validated high-throughput approach to screen for NIS inhibitors in the ToxCast phase I library, representing 293 important environmental chemicals.

Effects of chronic exposure to triclosan on reproductive and thyroid endpoints in the adult Wistar female rat.

Triclosan (TCS), an antibacterial, has been shown to be an endocrine disruptor in the rat. Previously, subchronic TCS treatment to female rats was found to advance puberty and potentiate the effect of ethinyl estradiol (EE) on uterine growth when EE and TCS were co-administered prior to weaning. In the pubertal study, a decrease in serum thyroxine (T) concentrations with no significant change in serum thyroid-stimulating hormone (TSH) was also observed.

Development of a screening approach to detect thyroid disrupting chemicals that inhibit the human sodium iodide symporter (NIS).

The U.S. EPA's Endocrine Disruptor Screening Program aims to use high-throughput assays and computational toxicology models to screen and prioritize chemicals that may disrupt the thyroid signaling pathway.

Crosstalk between the HpArsRS two-component system and HpNikR is necessary for maximal activation of urease transcription.

Helicobacter pylori NikR (HpNikR) is a nickel dependent transcription factor that directly regulates a number of genes in this important gastric pathogen. One key gene that is regulated by HpNikR is ureA, which encodes for the urease enzyme. In vitro DNA binding studies of HpNikR with the ureA promoter (PureA ) previously identified a recognition site that is required for high affinity protein/DNA binding.

Perilipin 5 regulates islet lipid metabolism and insulin secretion in a cAMP-dependent manner: implication of its role in the postprandial insulin secretion.

Elevation of circulating fatty acids (FA) during fasting supports postprandial (PP) insulin secretion that is critical for glucose homeostasis and is impaired in diabetes. We tested our hypothesis that lipid droplet (LD) protein perilipin 5 (PLIN5) in β-cells aids PP insulin secretion by regulating intracellular lipid metabolism. We demonstrated that PLIN5 serves as an LD protein in human islets.

Pancreatic islet neuropeptide Y overexpression has minimal effect on islet morphology and β-cell adaptation to high-fat diet.

Neuropeptide Y (NPY) is highly expressed in the hypothalamus, where it regulates feeding and energy homeostasis. Interestingly, NPY and its receptors are also expressed in peripheral tissues with roles in metabolism, including pancreatic islets. In islets, NPY is known to suppress insulin secretion acutely.

Repetitive sequence variations in the promoter region of the adhesin-encoding gene sabA of Helicobacter pylori affect transcription.

The pathogenesis of diseases elicited by the gastric pathogen Helicobacter pylori is partially determined by the effectiveness of adaptation to the variably acidic environment of the host stomach. Adaptation includes appropriate adherence to the gastric epithelium via outer membrane protein adhesins such as SabA. The expression of sabA is subject to regulation via phase variation in the promoter and coding regions as well as repression by the two-component system ArsRS.

Evaluation of hydroxyatrazine in the endocrine disruptor screening and testing program's male and female pubertal protocols.

Two critical components of the validation of any in vivo screening assay are to demonstrate sensitivity and specificity. Although the Endocrine Disruptor Screening Program's Tier 1 Male and Female Pubertal Protocols have been shown to be sensitive assays for the detection of weak endocrine disrupting chemicals (EDCs), there are concerns that the assays lack specificity for EDC effects when a chemical induces systemic toxicity. A lack of specificity, or the ability to correctly identify an inactive or "negative" chemical, would increase the probability of identifying false positives.

The effect of triclosan on the uterotrophic response to extended doses of ethinyl estradiol in the weanling rat.

Triclosan (TCS), an antibacterial, has been shown to be an endocrine disruptor in the rat. We reported previously that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth in rats exposed to EE and TCS in the uterotrophic assay, whereas TCS alone had no effect. To further characterize this potentiation, we evaluated the effect of co-exposure with lower doses of EE that are comparable to the concentrations in hormone replacement regimens and began to assess the mechanisms by which this potentiation occurs.

Polymorphisms of the acid sensing histidine kinase gene arsS in Helicobacter pylori populations from anatomically distinct gastric sites.

Phase variation is frequently utilized by bacterial species to affect gene expression such that phenotypic variants are maintained within populations, ensuring survival as environmental or host conditions change. Unusual among Helicobacter pylori phase variable or contingency genes is arsS, encoding a sensory histidine kinase involved in the acid acclimation of the organism. The presence of a 3' homopolymeric cytosine tract of variable length in arsS among Helicobacter pylori strains allows for the expression of various functional ArsS isoforms, differing in carboxy-terminal protein domains.