Explore the vast range of titles available.

A community engaged research (CER) approach was used to provide an exposure assessment of poly- and perfluorinated (PFAS) compounds in North Carolina residential drinking water. Working in concert with community partners, who acted as liaisons to local residents, samples were collected by North Carolina residents from three different locations along the Cape Fear River basin: upper, middle, and lower areas of the river. Residents collected either drinking water samples from their homes or recreational water samples from near their residence that were then submitted by the community partners for PFAS analysis. All samples were processed using weak anion exchange (WAX) solid phase extraction and analyzed using a non-targeted suspect screening approach as well as a quantitative approach that included a panel of 45 PFAS analytes, several of which are specific to chemical industries near the collection site locations. The non-targeted approach, which utilized a suspect screening list (obtained from EPA CompTox database) identified several PFAS compounds at a level two confidence rating (Schymanski scale); compounds identified included a fluorinated insecticide, a fluorinated herbicide, a PFAS used in polymer chemistry, and another that is used in battery production. Notably, at several locations, PFOA (39.8 ng/L) and PFOS (205.3 ng/L) were at levels that exceeded the mandatory EPA maximum contaminant level (MCL) of 4 ng/L. Additionally, several sites had detectable levels of PFAS that are unique to a local chemical manufacturer. These findings were communicated back to the community partners who then disseminated this information to the local residents to help empower and aid in making decisions for reducing their PFAS exposure.

To address the challenges of tracking the multitude of signaling molecules and metabolites that is the basis of biological complexity, we describe a strategy to expand the analytical techniques for dynamic systems biology. Using microfluidics, online desalting, and mass spectrometry technologies, we constructed and validated a platform well suited for sampling the cellular microenvironment with high temporal resolution. Our platform achieves success in: automated cellular stimulation and microenvironment control; reduced non-specific adsorption to polydimethylsiloxane due to surface passivation; real-time online sample collection; near real-time sample preparation for salt removal; and real-time online mass spectrometry. When compared against the benchmark of \"in-culture\" experiments combined with ultraperformance liquid chromatography-electrospray ionization-ion mobility-mass spectrometry (UPLC-ESI-IM-MS), our platform alleviates the volume challenge issues caused by dilution of autocrine and paracrine signaling and dramatically reduces sample preparation and data collection time, while reducing undesirable external influence from various manual methods of manipulating cells and media (e.g., cell centrifugation). To validate this system biologically, we focused on cellular responses of Jurkat T cells to microenvironmental stimuli. Application of these stimuli, in conjunction with the cell's metabolic processes, results in changes in consumption of nutrients and secretion of biomolecules (collectively, the exometabolome), which enable communication with other cells or tissues and elimination of waste. Naïve and experienced T-cell metabolism of cocaine is used as an exemplary system to confirm the platform's capability, highlight its potential for metabolite discovery applications, and explore immunological memory of T-cell drug exposure. Our platform proved capable of detecting metabolomic variations between naïve and experienced Jurkat T cells and highlights the dynamics of the exometabolome over time. Upregulation of the cocaine metabolite, benzoylecgonine, was noted in experienced T cells, indicating potential cellular memory of cocaine exposure. These metabolomics distinctions were absent from the analogous, traditional \"in-culture\" UPLC-ESI-IM-MS experiment, further demonstrating this platform's capabilities.

We use shotgun proteomics to identify biomarkers of diagnostic and prognostic value in individuals diagnosed with amyotrophic lateral sclerosis. Matched cerebrospinal and plasma fluids were subjected to abundant protein depletion and analyzed by nano-flow liquid chromatography high resolution tandem mass spectrometry. Label free quantitation was used to identify differential proteins between individuals with ALS (n = 33) and healthy controls (n = 30) in both fluids. In CSF, 118 (p-value < 0.05) and 27 proteins (q-value < 0.05) were identified as significantly altered between ALS and controls. In plasma, 20 (p-value < 0.05) and 0 (q-value < 0.05) proteins were identified as significantly altered between ALS and controls. Proteins involved in complement activation, acute phase response and retinoid signaling pathways were significantly enriched in the CSF from ALS patients. Subsequently various machine learning methods were evaluated for disease classification using a repeated Monte Carlo cross-validation approach. A linear discriminant analysis model achieved a median area under the receiver operating characteristic curve of 0.94 with an interquartile range of 0.88–1.0. Three proteins composed a prognostic model (p = 5e-4) that explained 49% of the variation in the ALS-FRS scores. Finally we investigated the specificity of two promising proteins from our discovery data set, chitinase-3 like 1 protein and alpha-1-antichymotrypsin, using targeted proteomics in a separate set of CSF samples derived from individuals diagnosed with ALS (n = 11) and other neurological diseases (n = 15). These results demonstrate the potential of a panel of targeted proteins for objective measurements of clinical value in ALS.

Per- and polyfluoroalkyl substances (PFAS) are used extensively in commercial products. Their unusual solubility properties make them an ideal class of compounds for various applications. However, these same properties have led to significant contamination and bioaccumulation given their persistence in the environment. Development of analytical techniques to detect and quantify these compounds must take into account the potential for these properties to perturb these measurements, specifically the potential to bias the electrospray ionization (ESI) process. Direct injection ESI analysis of 23 different PFAS species revealed that hydrophobicity and PFAS class can predict the ESI overall response factors. In this study, a method for predicting the behavior of individual PFAS compounds, including relative retention order in chromatography, is presented which is simply based on the number of fluorine atoms in the molecule as well as the class of the compound (e.g., perfluroalkylcarboxylic acids) vs. computational estimations (e.g., non-polar surface area and logP).

Per-and polyfluoroalkyl substances (PFAS) are ubiquitous contaminants in freshwater ecosystems. Many PFAS are incorporated into food webs, with potential effects on ecological and human health. However, PFAS incorporation into the base of aquatic food webs remains poorly understood. The goal of this study was to quantify the uptake and trophic transfer of both legacy and current use PFAS compounds using a simulated freshwater food chain in a lab setting. Natural periphytic biofilms were placed into trays containing equimolar binary aqueous PFAS mixtures at environmentally relevant concentrations for five days. Following the initial exposure period, newly hatched mayfly larvae were introduced into each tray to feed on periphyton for most of their larval development. The mature larvae were then fed to zebrafish. All water and biota samples contained detectable levels of the tested PFAS. All PFAS were more concentrated in periphyton than in water, and four of six PFAS were further concentrated in mayfly larvae relative to periphyton. PFDA was the most accumulative in all biota. PFAS concentrations in zebrafish were significantly correlated with those in larval mayflies. Assimilation efficiencies in zebrafish were high (>70%) for all compounds. Bioaccumulation of PFAS in periphyton and mayflies was positively correlated with log K and number of carbons.

Perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoA, DTXSID50723994) is a perfluoroalkyl ether acid (PFEA) produced at a fluorochemical facility (\"Fayetteville Works\") in Bladen County, North Carolina. In 2015, PFO5DoA was first identified in Cape Fear River water samples collected downstream of the facility's wastewater discharge point. Approximately 280,000 people rely on public water sourced from the lower Cape Fear River. The GenX Exposure Study started in 2017 to characterize PFEA exposure in Cape Fear River Basin, North Carolina, residents. We detected three PFEAs-ethanesulfonic acid, 2-[1-[difluoro(1,2,2,2-tetrafluoroethoxy)methyl]-1,2,2,2-tetrafluoroethoxy]-1,1,2,2-tetrafluoro- (also known as Nafion by-product 2, DTXSID10892352); perfluoro (3,5,7,9-butaoxadecanoic) acid (PFO4DA, DTXSID90723993); and PFO5DoA-in blood serum from nearly all 344 participants who resided in Wilmington, North Carolina, and provided blood samples in 2017 and 2018. The final dataset contained 80 reanalyzed and 308 predicted concentrations for the 388 samples. For the 80 samples reanalyzed by LCHRMS, predictions of the corrected concentrations were strongly correlated with the concentrations determined by reanalysis (rs = 0:94).

Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic, fluorinated chemicals. Wastewater discharges from a fluorochemical manufacturing facility (\"Fayetteville Works\") contaminated the lower Cape Fear River in North Carolina with per- and polyfluoroalkyl ether acids (PFEAs),2 a subgroup of PFAS. The GenX Exposure Study aims to characterize exposure to PFAS in Cape Fear River Basin, North Carolina, residents. The study started in 2017 with Wilmington, North Carolina, residents who were exposed to PFEAs through municipal water derived from the lower Cape Fear River. Hydro-EVE was detected in 39 out of 80 (49%) serum samples from Wilmington participants, 2017-2018, at concentrations below 1 ng=mL (95th percentile = 0:47 ng=mL) (Table 1), whereas 6:2 FTS was infrequently detected (one sample had 2 ng=mL 6:2 FTS and seven samples had detectable, but nonquantifiable levels

Journal Article

Share this book

Add to My Shelf