TY - JOUR TI - PFAS are forever? The state of the science and research needs for analyzing and treating PFAS‐laden water AU - Speth, Thomas AU - Crimi, Michelle AU - Chowdhury, Zaid AU - Dickenson, Eric AU - Guelfo, Jennifer AU - Knappe, Detlef AU - Liu, Jinxia AU - Leeson, Andrea T2 - AWWA Water Science AB - Readers will benefit from learning about the current status of PFAS sampling, analysis, and treatment techniques. The unique properties of PFAS can cause problems when conducting basic bench or field studies. For instance, the bottle choice is important not only for assuring accurate analytical measurements, but also for the design of the studies themselves. In this topical collection, Kleiner et al. (2021) assess the practical implications of using various bottle materials in ion exchange (IX) or activated carbon isotherm experiments. Silanized glass, polypropylene, and high-density polyethylene (HDPE) were screened. It is shown that five perfluoroalkyl sulfonic acids (PFSA) sorbed to HDPE bottles, and linear isomers of two PFSA exhibited enhanced adsorption relative to corresponding branched isomers. From these results, guidance for conducting IX and activated carbon isotherm studies are developed. For sampling in the field, a demonstrated passive sampling technique would be extremely important because of the vagaries of PFAS concentrations seen in natural environments. Hartmann et al. (2021) demonstrate a passive sampler that can be used for PFAS, including C4-C9 perfluorocarboxylates (PFCAs) and C4, C6, and C8 perfluorosulfonates (PFSAs) under a variety of solution conditions. The sampler uses a PFAS-specific adsorbent tailored for both hydrophobic and IX interactions. The adsorbent is an organosilica resin modified with cross-linked amine polymer with the addition of amine groups in combination with Cu2+. The samplers show an integrated linear response to concentration with time with all PFAS analytes tested except for short-chain PFAS (i.e., C4 and C5 PFCAs), and relatively low variability in sampling rate is demonstrated over a range of conditions including water matrices with elevated ionic strength and natural organic matter concentrations. Sampling times as short as 3 days are necessary to reach detection limits <70 ng/L for PFOA and PFOS. Determination of PFAS sources is vital to protect drinking water sources. In this topical collection, Andrews et al. (2021) analyze the potential for environmental PFAS releases from contaminated sites, currently active industrial sites, and waste disposal sites. EPA's Enforcement and Compliance History Online (ECHO) database and specific case studies from Michigan and California demonstrate how PFAS source identification programs can provide crucial information for determining PFAS sources and therefore aid in developing effluent guidelines and pretreatment programs. With regard to analytic methods, at the time we started curating this topical issue, the only available EPA Methods were Methods 537.1 and 533 developed for drinking water. These methods have also been widely used for source water assessments because of the lack of ambient water methods. To date, few studies have been published to support expanding the methods to other water matrices. Whitaker et al. (2021) evaluate the performance of these two methods for use with both potable and nonpotable waters. Both methods are found to be generally applicable for the analysis of PFAS in pristine nonpotable water matrices. However, low biased recoveries are notable issues for long-chain PFAS or those that elute late in the reverse-phase column because of surface adsorption loss and the water matrix. Also, there are extraction concerns for those PFAS for which matched isotopically labeled standards are not available. These challenges are successfully resolved or reduced by enhancing post-extraction bottle rinsing and elution procedures. The results of Whitaker et al. (2021) illustrate the challenge of simultaneously analyzing an extensive suite of PFAS with diverse properties. EPA recently published Draft Method 1633 targeting 40 PFAS and applicable to aqueous solids and tissue samples. The method is undoubtedly of great interest to many, albeit beyond the scope of the current collection. Combustion ion chromatography (CIC) has been a valuable tool to determine total fluorine or total organic fluorine of environmental samples, but such a system is not commonly available. In this topical collection, Wang, Abusallout, et al. (2021), Wang, Yan, et al. (2021) tested the idea of modifying a total organic carbon analyzer—an instrument common in laboratories across disciplines—as an alternative approach. The modified system can serve as a screening technique or allow for a fluorine mass balance evaluation to help determine overall treatment or percent mineralization for destruction technologies. The hydrogen fluoride evolving from combusted samples is captured in the impinger and analyzed by ion chromatography. The method detection limit based on PFOA spiked samples is 36 μg-F/L (52 μg PFOA/L). River water and wastewater have similar recoveries to those spiked in deionized water. Wang, Abusallout, et al. (2021), Wang, Yan, et al. (2021) identified some previously unknown limitations of CIC methods: possible variable recoveries across PFAS of different chain lengths or structures, and inorganic fluorine loss during combustion. The study emphasizes that suitable extraction and inorganic fluoride removal techniques are essential in this analysis to best define whether it is total, organic, or adsorbable organic fluorine. A great deal of work has been published on PFAS treatment as referenced in the articles in this topical collection. However, the basic technologies that are commonly applied for PFAS removal from water have not changed since PFAS became a concern. These include granular activated carbon (GAC) adsorption, IX, and filtration through high-pressure membranes—that is, nanofiltration (NF) and reverse osmosis (RO) membranes. This is understandable knowing the length of time needed to move a novel technology into the marketplace, especially if it includes potable water production given the potential health consequences that may occur if the system is designed poorly. Also, there is a need to factor in all aspects of certifying and permitting a new technology through state primacy agencies. This is not insignificant for drinking water applications; however, for those dealing with remediation waters, industrial streams, landfill leachates, or residual streams from a drinking water treatment process (e.g., activated carbon, IX resins, and NF/RO membranes), novel technologies may find a niche from which they could expand to potable applications in the future. Technologies besides GAC, IX resins, and NF/RO membranes include foam separation techniques that take advantage of PFAS's propensity to accumulate at air/water interfaces or adsorption onto clays or biosolids; these may be less expensive and could also have properties that result in the ultimate disposal or destruction of PFAS. Also, destructive technologies have shown the potential for PFAS removal, as discussed in this topical issues, perhaps best suited for high concentration streams. As demonstrated in the articles of this topical collection, recent research is working to advance the application of specific PFAS treatments. Communities have struggled with determining treatment choices that are both robust and economical. This is especially true for communities dealing with additional contaminants besides PFAS. For very small communities or individual rural homes affected by groundwater contamination, home treatment systems can be an option to reduce exposure. As with other aspects of PFAS treatment, PFAS removal by household point-of-entry (POE) treatment systems is not well-established. In this topical collection, Natarajan et al. (2021) test a POE adsorption system to remove PFAS and their precursors in a groundwater contaminated with aqueous film-forming foam. As expected from the literature, the long-chain PFAS are more effectively removed than short-chain PFAS, and PFCAs break through before PFSAs of the same chain length. The TOP assay highlights that precursors of short-chain PFCAs break through the filter system earlier than the measured PFCAs and PFSAs, but at the same general time as the dissolved organic carbon (DOC). Overall, under these conditions, the studied POE filters show 5 months of effective removal for all the PFAS measured, and over 7 months for PFAS other than select shorter-chain PFCAs. The results of Natarajan et al. (2021) therefore show that the studied POE system can be effective in managing PFAS contamination. Also at the home system scale, Mulhern et al. (2021) show that in a study of 18 private wells in North Carolina, a commercially-available point of use (POU) carbon-block filter certified under NSF's P-473 protocol for PFOA and PFOS was successful in removing 17 PFAS detected in the filter influent, including short-chain perfluoroalkyl ether acids (PFEAs). The eight-month study covered the manufacturer's recommended lifetime for the device. Variations in the influent water quality (pH range of 4.4–7.1, DOC range of 0.6–1.2 mg/L) did not have a significant effect on performance. This study demonstrates that POU devices operated under manufacturer's guidelines can be an effective approach for treating PFAS contaminated water, although additional data are needed to determine whether a wider range of site-specific conditions such as PFAS concentration or background water quality may affect performance. IX treatment can have higher capacities as compared to GAC; however, higher media costs result in an unclear situation as to which media is the most cost-effective to achieve a final target concentration in any given water. As with GAC, optimization of IX resins is a research need, including evaluation of regenerable resins. To date, most systems have employed single-use resins. In this topical collection, Dietz et al. (2021) evaluate the regeneration efficiency of strong-base anion exchange resins for various PFAS concentrations, polymer compositions, and regeneration solutions. Generally, it is shown that a higher PFAS concentration in the influent resulted in higher PFAS loading on the resin and higher regeneration efficiency, and this was especially true for the polystyrene resin. Polystyrene resins showed greater removal of PFSAs than PFCAs, and greater removal of long-chain PFAAs than short-chain analogs. The presence of organic cosolvents in the regenerant brine also improved regeneration efficiency. Treatment performance models are useful in anticipating how a full-scale design will function when conditions or situations change, such as varying influent PFAS concentrations, flow rates, and future treatment goals. Compared with GAC models, there are few IX treatment models freely available. In this topical collection, Haupert et al. (2021) discuss important theoretical and practical considerations for modeling PFAS removal from drinking water using gel-type, strong base anion exchange resin in batch and column processes. It is shown that several important limitations found in the literature preclude movement toward model development, including the use of inappropriate isotherms and not accounting for non-equilibrium conditions. Theoretical considerations are presented that will help future researchers develop models based on basic ion-exchange theory, and for designing and interpreting the results of both batch and column experiments. Similarly, Kempisty et al. (2022) evaluate adsorption of 10 PFAAs onto two sub-bituminous, coal-based GACs at the bench-, pilot-, and full-scales to evaluate GAC scale-up procedures and to determine the effects of PFAA characteristics and background organic matter on carbon use rates. Batch tests with pulverized GAC show the GACs perform similarly in groundwater, but the GAC with the larger mesopore volume is more effective for PFAA removal in surface water. The proportional diffusivity rapid small-scale column tests (RSSCTs) overpredicted full-scale capacity. The column tests show that carbon use rates decrease with increasing PFAS chain length and are lower for groundwater than for surface water. No differences are observed for empty bed contact times of 13 and 26 min in the full-scale adsorbers treating groundwater or in the proportional diffusivity RSSCT experiments. Based on a carbon use rate of <25 mgGAC/Lwater treated as a criterion for feasibility, the field-scale GAC adsorber data suggest GAC is a viable treatment option for long-chain and some short-chain PFAAs. GAC and IX resins are the standard adsorbents generally accepted for PFAS treatment; however, there are numerous formulations for these adsorbents. Also, there are other more novel media that are known to remove organic contaminants. A media's acceptability is a function of many issues such as performance, cost, operational requirements, impacts on general water quality, and regulatory acceptance. In this topical collection, Li et al. (2021) review and discuss the potential of using functional bioadsorbents as low-cost alternatives to traditional adsorbents, and of particular interest is their potential removal of short-chain PFAS. The authors state that nano-scale biosorbents can be derived and properly functionalized in a cost-effective manner from raw biomass. The functionalized biomass sorbents were shown to effectively remove short-chain PFAS. Najm et al. (2021) presented RSSCT results for three commercially available bituminous coal-based GACs and one clay-based adsorbent containing quaternary ammonium groups. The three GACs are shown to perform similarly with initial breakthrough starting around 100,000 bed volumes except for PFBS (C4 PFSA) and PFHxA (C6 PFCA), which showed initial breakthrough at around 50,000 bed volumes. For the clay-based adsorbent, PFHxA was the only studied PFAS that appeared in the column effluent after treating 300,000 bed volumes. Similar to IX resins, the clay-based sorbent could be operated at a shorter empty bed contact time and higher hydraulic loading rate compared to GAC. Grieco et al. (2021) expand on this theme by presenting batch equilibrium and RSSCT results for activated carbon and an emerging modified clay sorbent using drinking water with similar PFAS composition but varying dissolved organic carbon concentrations. Under the conditions tested, both batch equilibrium and flow-through column experiments demonstrate that the modified clay has a greater adsorptive capacity and faster adsorption kinetics compared to activated carbon for select long- (PFOA) and short-chain PFAS (PFBS). Adsorbent treatment schemes are employed in treatment plants to produce potable water, but they are also used in the subsurface to control the migration of contaminants. Wang, Yan, et al. (2021) show through batch experiments that modified bentonite clays and GAC can help minimize PFAS leaching from contaminated soils, which are long-term PFAS sources to groundwater and surface water. The modified clay is shown to perform the best in immobilizing many anionic PFAS whereas GAC is demonstrated to be most effective in preventing leaching of select cationic PFAS. Hardwood biochar, despite good performance in deionized water, is shown to have minor or negligible effects for all studied PFAS classes when present in soil slurry. Overall, the study shows potential options for reducing leaching from contaminated soils to minimize the continuous release of PFAS into water. It is known that certain PFAS are poorly removed by GAC and IX resins, even in clean water matrices. There are no clear treatment choices for difficult to treat water. RO and NF membranes generally reject PFAS to a great degree, but because these separation processes do not destroy PFAS, they produce a concentrated waste stream. Therefore, there is a need to develop treatment technologies that can treat waste streams to prevent environmental and potential human exposure, possibly at geographically distant locations. In this topical collection, Tow et al. (2021) review a wide range of possible destruction, concentration, and sequestration strategies for the treatment of RO and NF concentrate streams. Cost issues are paramount, given the costs of both the initial membrane separation of PFAS and any subsequent concentrate management strategy. The issues with membrane retentate streams also apply to other hard-to-treat waters such as landfill leachates, remediation waters, and wastewaters. To identify approaches for treating residuals from non-destructive water treatment processes, Ryan et al. (2021) review electrochemical technologies such as electrocoagulation and electrooxidation. It is found that electrochemical treatment is also promising for residual streams of IX, NF, and RO processes. However, much work must be completed to account for environmentally relevant PFAS concentrations, high conductivity, and natural organic matter, limitations in treating short-chain PFAS, transformation products, and a community's technical and financial limitations. McCleaf et al. (2021) examine foam fractionation treatment of landfill leachate. Foam fractionation is shown to give removal efficiencies of greater than 90% for PFOA, PFOS, PFHxS, and PFHpA, and 6:2 FTSA; between 50% and 80% removal for other PFAS such as PFNA, PFPeS, PFHxA, PFHpS, and PFBS; and 20%–50% removal for EtFOSAA, PFBA, PFDA, FOSA, PFPeA, and MeFOSAA. Increased removal efficiencies for the majority of the PFAS are demonstrated when the flowrate is increased, iron (III) oxide coagulant is added, conductivity is increased, and higher influent PFAS concentrations are applied. Wastewaters can be challenging to treat and present possible health effects when considering reuse applications. Kumar et al. (2021) present data from the City of Altamonte Springs' potable reuse demonstration facility. The combination of ozonation, biological activated carbon filtration, ultrafiltration, GAC adsorption, and UV advanced oxidation shows the removal of long-chain PFAS (greater than five carbons for PFSA and greater than six carbons for PFCA) when the GAC adsorbers were operated to the point that would keep effluent TOC levels to below 3 mg/L, which is the regulatory limit in Florida for indirect potable reuse. Ozone followed by biological filtration increased PFAS concentrations due to oxidation of PFAS precursor material. GAC was determined to be the critical process for removing both PFAS and TOC, and the study shows the treatment trade-offs in a water reuse operation. Likewise, Gonzalez et al. (2021) present a project at Hampton Roads Sanitation District (HRSD), which recently initiated an indirect potable reuse project to recharge the Potomac Aquifer. The results show source control and GAC treatment maintained low concentrations of long-chain PFAAs (<8 ppt sum of PFOA, PFNA, PFDA, PFHxS, PFOS). Early breakthrough in the GAC column for short-chain PFAS (i.e., PFBA, PFPeA, PFHxA) and the high mobility of PFAS in the Potomac Aquifer support strict source control measures and the use of TOC to guide GAC operation. In the United States, the Safe Drinking Water Act authorizes EPA to set national health-based standards for drinking water to protect against both naturally-occurring and man-made contaminants found in drinking water. In this topical collection, Alfredo et al. (2021) use a Relative Health Index (RHI) metric to quantify ranges of potential health risk reductions from state and federal PFAS threshold concentrations, and compare them with previous regulatory determinations—for example, arsenic and uranium—as well as with several currently unregulated contaminants. Alfredo et al. (2021) propose that given certain assumptions, the threshold concentrations for PFOA and PFOS derived from a number of references are not expected to achieve meaningful health risk reduction nationally (in the United States) compared with historically established benchmarks given known occurrence data. This study emphasizes the balance in regulatory decision-making between public health protection and the associated costs in the face of data uncertainty. Due to the absence of, or differing, PFAS regulations, strategies are needed to communicate with the public clearly and effectively. Such communication can be challenging because of existing public opinion as well as the complexity of PFAS and their behaviors in the environment and through treatment. Harclerode et al. (2021) demonstrate a community-specific adaptive risk communication strategy that can allow municipalities to perform assessment and mitigation activities while addressing community concerns. This is demonstrated by two outreach strategies that addressed the respective municipality's planned communication messages following PFAS assessment actions. The two approaches demonstrate that risk perception factors differed, and hence a community-specific approach is likely needed for other cases. The authors point to the value of community engagement in developing risk management solutions. As shown in this topical collection, a great deal of research is being conducted on the analysis and treatment of PFAS. The question remains as to whether PFAS can be mineralized or put into a state that will cause no further harm to the environment or the public. Analytical methods are improving in several areas, such as the ability to cover additional analytes in a wider range of matrices such as those found in treatment process residual streams, and standardizing techniques that bring down the cost and level of effort needed for analysis. Measurement parameters such as total adsorbable fluorine will be helpful as a screening technique, and offer the potential for helping close the fluorine mass balance for destructive processes. For treatment, GAC, IX, and NF/RO membranes remain proven processes for water treatment that will be considered by contaminated sites and utilities, especially for water sources that are not highly contaminated. GAC and IX are effective treatment processes for long-chain PFAS, but the specifics of treatment are shaped by site-specific factors. Each of these processes, however, have residual streams that need to be managed, and much is still to be learned regarding GAC reactivation, IX resin regeneration or incineration, and NF/RO concentrate treatment. Other novel technologies continue to be developed, and there is hope they will be up to the challenge of treating process residual streams and other hard-to-treat waters such as landfill leachates, wastewaters, membrane concentrates, and highly contaminated waters. Further research is needed. Thomas Speth: Writing – original draft; writing – review and editing. Jinxia Liu: Writing – review and editing. Detlef Knappe: Writing – review and editing. Andrea Leeson: Writing – review and editing. Zaid Chowdhury: Writing – review and editing. Michelle Crimi: Writing – original draft; writing – review and editing. Jennifer Guelfo: Writing – review and editing. Eric Dickenson: Writing – review and editing. Data sharing not applicable to this article as no datasets were generated or analyzed for this editorial. DA - 2022/3// PY - 2022/3// DO - 10.1002/aws2.1276 UR - https://doi.org/10.1002/aws2.1276 ER - TY - JOUR TI - Granular activated carbon adsorption of perfluoroalkyl acids from ground and surface water AU - Kempisty, David M. AU - Arevalo, Elisa AU - Spinelli, Allison M. AU - Edeback, Viking AU - Dickenson, Eric R. V. AU - Husted, Courtney AU - Higgins, Christopher P. AU - Summers, R. Scott AU - Knappe, Detlef R. U. T2 - AWWA Water Science AB - Abstract Adsorption of perfluoroalkyl acids (PFAAs) by granular activated carbon (GAC) was evaluated in bench‐, pilot‐, and full‐scale studies to determine effects of PFAA characteristics and background organic matter on carbon use rates. Rapid small‐scale column tests (RSSCTs) were conducted according to the proportional diffusivity (PD) design to assess their suitability to predict full‐ or pilot‐scale GAC performance. PFAA removal from groundwater (GW) and coagulated surface water (SW) was studied with two sub‐bituminous coal‐based GACs. In batch tests conducted with pulverized GAC, the GACs performed similarly in GW, but the GAC with the larger mesopore volume was more effective for PFAA removal from SW. In column tests, carbon use rates decreased with increasing PFAA chain length and were lower for GW (total organic carbon [TOC] = 0.7 mg/L) than for SW (TOC = 2.0–2.7 mg/L). The volume of SW that could be treated to 10% or 50% PFAA breakthrough was about 50–60% of the volume of GW that could be treated when comparing pilot‐scale data for SW with full‐scale data for GW. Consistent differences in PFAA adsorption capacity were not observed for empty bed contact times of 13 and 26 min in full‐scale adsorbers treating GW. The PD‐RSSCT simulating PFAA removal from GW consistently overpredicted full‐scale adsorption capacity, on average by ~70%. Using a carbon use rate of <25 mg GAC /L water treated ) as a criterion for the feasibility of GAC treatment, full‐ and pilot‐scale GAC adsorber data suggest that GAC is a viable treatment option (carbon use rate < 25 mg GAC /L water treated ) for perfluoroalkylcarboxylic acids with six or more carbon atoms in SW and five or more carbon atoms in GW. For perfluoroalkyl sulfonic acids, GAC treatment is viable for compounds containing four or more carbons based on results obtained with both SW and GW. DA - 2022/1// PY - 2022/1// DO - 10.1002/aws2.1269 UR - https://doi.org/10.1002/aws2.1269 ER - TY - JOUR TI - Correction to “Per- and Polyfluoroalkyl Substance (PFAS) Transport from Groundwater to Streams near a PFAS Manufacturing Facility in North Carolina, USA” AU - Pétré, Marie-Amélie AU - Genereux, David P. AU - Koropeckyj-Cox, Lydia AU - Knappe, Detlef R. U. AU - Duboscq, Sandrine AU - Gilmore, Troy E. AU - Hopkins, Zachary R. T2 - Environmental Science & Technology AB - ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to “Per- and Polyfluoroalkyl Substance (PFAS) Transport from Groundwater to Streams near a PFAS Manufacturing Facility in North Carolina, USA”Marie-Amélie Pétré*Marie-Amélie PétréMore by Marie-Amélie Pétréhttps://orcid.org/0000-0001-7975-7476, David P. Genereux*David P. GenereuxMore by David P. Genereux, Lydia Koropeckyj-CoxLydia Koropeckyj-CoxMore by Lydia Koropeckyj-Cox, Detlef R. U. KnappeDetlef R. U. KnappeMore by Detlef R. U. Knappehttps://orcid.org/0000-0003-1315-1791, Sandrine DuboscqSandrine DuboscqMore by Sandrine Duboscq, Troy E. GilmoreTroy E. GilmoreMore by Troy E. Gilmore, and Zachary R. HopkinsZachary R. HopkinsMore by Zachary R. HopkinsCite this: Environ. Sci. Technol. 2022, 56, 12, 9145Publication Date (Web):June 1, 2022Publication History Published online1 June 2022Published inissue 21 June 2022https://doi.org/10.1021/acs.est.2c03111Copyright © 2022 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views446Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (484 KB) Get e-Alerts Get e-Alerts DA - 2022/6/21/ PY - 2022/6/21/ DO - 10.1021/acs.est.2c03111 VL - 56 IS - 12 SP - 9145-9145 UR - https://doi.org/10.1021/acs.est.2c03111 ER - TY - JOUR TI - Temporal chemical composition changes in water below a crude oil slick irradiated with natural sunlight AU - Roman-Hubers, Alina T. AU - Aeppli, Christoph AU - Dodds, James N. AU - Baker, Erin S. AU - McFarlin, Kelly M. AU - Letinski, Daniel J. AU - Zhao, Lin AU - Mitchell, Douglas A. AU - Parkerton, Thomas F. AU - Prince, Roger C. AU - Nedwed, Tim AU - Rusyn, Ivan T2 - MARINE POLLUTION BULLETIN AB - Photooxidation can alter the environmental fate and effects of spilled oil. To better understand this process, oil slicks were generated on seawater mesocosms and exposed to sunlight for 8 days. The molecular composition of seawater under irradiated and non-irradiated oil slicks was characterized using ion mobility spectrometry-mass spectrometry and polyaromatic hydrocarbons analyses. Biomimetic extraction was performed to quantify neutral and ionized constituents. Results show that seawater underneath irradiated oil showed significantly higher amounts of hydrocarbons with oxygen- and sulfur-containing by-products peaking by day 4-6; however, concentrations of dissolved organic carbon were similar. Biomimetic extraction indicated toxic units in irradiated mesocosms increased, mainly due to ionized components, but remained <1, suggesting limited potential for ecotoxicity. Because the experimental design mimicked important aspects of natural conditions (freshly collected seawater, natural sunlight, and relevant oil thickness and concentrations), this study improves our understanding of the effects of photooxidation during a marine oil spill. DA - 2022/12// PY - 2022/12// DO - 10.1016/j.marpolbul.2022.114360 VL - 185 SP - SN - 1879-3363 KW - Oil KW - Photodegradation KW - Photooxidation KW - Petroleomics KW - Toxicity KW - Spill ER - TY - JOUR TI - Confirmation of high-throughput screening data and novel mechanistic insights into FXR-xenobiotic interactions by orthogonal assays AU - Hamm, Jon AU - Mahapatra, Debabrata AU - Knuth, Megan M. AU - Abedini, Jaleh AU - Lingerfelt, Mary AU - Ekins, Sean AU - Kullman, Seth W. T2 - CURRENT RESEARCH IN TOXICOLOGY AB - Toxicology in the 21st Century (Tox21) is a federal collaboration employing a high-throughput robotic screening system to test 10,000 environmental chemicals. One of the primary goals of the program is prioritizing toxicity evaluations through in vitro high-throughput screening (HTS) assays for large numbers of chemicals already in commercial use for which little or no toxicity data is available. Within the Tox21 screening program, disruption in nuclear receptor (NR) signaling represents a particular area of interest. Given the role of NR's in modulating a wide range of biological processes, alterations of their activity can have profound biological impacts. Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that has demonstrated importance in bile acid homeostasis, glucose metabolism, lipid homeostasis and hepatic regeneration. In this study, we re-evaluated 24 FXR agonists and antagonists identified through Tox21 using select orthogonal assays. In transient transactivation assays, 7/8 putative agonists and 4/4 putative inactive compounds were confirmed. Likewise, we confirmed 9/12 antagonists tested. Using a mammalian two hybrid approach we demonstrate that both FXR agonists and antagonists facilitate FXRα-coregulator interactions suggesting that differential coregulator recruitment may mediate activation/repression of FXRα mediated transcription. Additionally, we tested the ability of select FXR agonists and antagonists to facilitate hepatic transcription of FXR gene targets Shp and Bsep in a teleost (Medaka) model. Through application of in vitro cell-based assays, in silico modeling and in vivo gene expressions, we demonstrated the molecular complexity of FXR:ligand interactions and confirmed the ability of diverse ligands to modulate FXRα, facilitate differential coregulator recruitment and activate/repress receptor-mediated transcription. Overall, we suggest a multiplicative approach to assessment of nuclear receptor function may facilitate a greater understanding of the biological and mechanistic complexities of nuclear receptor activities and further our ability to interpret broad HTS outcomes. DA - 2022/// PY - 2022/// DO - 10.1016/j.crtox.2022.100092 VL - 3 SP - SN - 2666-027X KW - ToxCast KW - Farnesoid X receptor KW - High -throughput screening KW - Teleost models KW - Medaka ER - TY - JOUR TI - Mapping glycine uptake and its metabolic conversion to glutathione in mouse mammary tumors using functional mass spectrometry imaging AU - Mellinger, Allyson L. AU - Kibbe, Russell R. AU - Rabbani, Zahid N. AU - Meritet, Danielle AU - Muddiman, David C. AU - Gamcsik, Michael P. T2 - FREE RADICAL BIOLOGY AND MEDICINE AB - Although glutathione plays a key role in cancer cell viability and therapy response there is no clear trend in relating the level of this antioxidant to clinical stage, histological grade, or therapy response in patient tumors. The likely reason is that static levels of glutathione are not a good indicator of how a tissue deals with oxidative stress. A better indicator is the functional capacity of the tissue to maintain glutathione levels in response to this stress. However, there are few methods to assess glutathione metabolic function in tissue. We have developed a novel functional mass spectrometry imaging (fMSI) method that can map the variations in the conversion of glycine to glutathione metabolic activity across tumor tissue sections by tracking the fate of three glycine isotopologues administered in a timed sequence to tumor-bearing anesthetized mice. This fMSI method generates multiple time point kinetic data for substrate uptake and glutathione production from each spatial location in the tissue. As expected, the fMSI data shows glutathione metabolic activity varies across the murine 4T1 mammary tumor. Although glutathione levels are highest at the tumor periphery there are regions of high content but low metabolic activity. The timed infusion method also detects variations in delivery of the glycine isotopologues thereby providing a measure of tissue perfusion, including evidence of intermittent perfusion, that contributes to the observed differences in metabolic activity. We believe this new approach will be an asset to linking molecular content to tissue function. DA - 2022/11/20/ PY - 2022/11/20/ DO - 10.1016/j.freeradbiomed.2022.11.010 VL - 193 SP - 677-684 SN - 1873-4596 ER - TY - JOUR TI - On the importance of color in mass spectrometry imaging AU - Knizner, Kevan T. AU - Kibbe, Russell R. AU - Garrard, Kenneth P. AU - Nunez, Jamie R. AU - Anderton, Christopher R. AU - Muddiman, David C. T2 - JOURNAL OF MASS SPECTROMETRY AB - Mass spectrometry imaging (MSI) data visualization relies on heatmaps to show the spatial distribution and measured abundances of molecules within a sample. Nonuniform color gradients such as jet are still commonly used to visualize MSI data, increasing the probability of data misinterpretation and false conclusions. Also, the use of nonuniform color gradients and the combination of hues used in common colormaps make it challenging for people with color vision deficiencies (CVDs) to visualize and accurately interpret data. Here we present best practices for choosing a colormap to accurately display MSI data, improve readability, and accommodate all CVDs. We also provide other resources on the misuse of color in the scientific field and resources on scientifically derived colormaps presented herein. DA - 2022/12// PY - 2022/12// DO - 10.1002/jms.4898 VL - 57 IS - 12 SP - SN - 1096-9888 KW - colormap KW - CVD KW - data visualization KW - MSI ER - TY - JOUR TI - A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior AU - Starnes, Hannah M. AU - Rock, Kylie D. AU - Jackson, Thomas W. AU - Belcher, Scott M. T2 - Frontiers in Toxicology AB - Per- and polyfluoroalkyl substances (PFAS) are a class of structurally diverse synthetic organic chemicals that are chemically stable, resistant to degradation, and persistent in terrestrial and aquatic environments. Widespread use of PFAS in industrial processing and manufacturing over the last 70 years has led to global contamination of built and natural environments. The brain is a lipid rich and highly vascularized organ composed of long-lived neurons and glial cells that are especially vulnerable to the impacts of persistent and lipophilic toxicants. Generally, PFAS partition to protein-rich tissues of the body, primarily the liver and blood, but are also detected in the brains of humans, wildlife, and laboratory animals. Here we review factors impacting the absorption, distribution, and accumulation of PFAS in the brain, and currently available evidence for neurotoxic impacts defined by disruption of neurochemical, neurophysiological, and behavioral endpoints. Emphasis is placed on the neurotoxic potential of exposures during critical periods of development and in sensitive populations, and factors that may exacerbate neurotoxicity of PFAS. While limitations and inconsistencies across studies exist, the available body of evidence suggests that the neurobehavioral impacts of long-chain PFAS exposures during development are more pronounced than impacts resulting from exposure during adulthood. There is a paucity of experimental studies evaluating neurobehavioral and molecular mechanisms of short-chain PFAS, and even greater data gaps in the analysis of neurotoxicity for PFAS outside of the perfluoroalkyl acids. Whereas most experimental studies were focused on acute and subchronic impacts resulting from high dose exposures to a single PFAS congener, more realistic exposures for humans and wildlife are mixtures exposures that are relatively chronic and low dose in nature. Our evaluation of the available human epidemiological, experimental, and wildlife data also indicates heightened accumulation of perfluoroalkyl acids in the brain after environmental exposure, in comparison to the experimental studies. These findings highlight the need for additional experimental analysis of neurodevelopmental impacts of environmentally relevant concentrations and complex mixtures of PFAS. DA - 2022/4/11/ PY - 2022/4/11/ DO - 10.3389/ftox.2022.881584 VL - 4 UR - http://dx.doi.org/10.3389/ftox.2022.881584 ER - TY - JOUR TI - Blood concentrations of per- and polyfluoroalkyl substances are associated with autoimmune-like effects in American alligators from Wilmington, North Carolina AU - Guillette, T. C. AU - Jackson, Thomas W. AU - Guillette, Matthew AU - McCord, James AU - Belcher, Scott M. T2 - FRONTIERS IN TOXICOLOGY AB - Surface and groundwater of the Cape Fear River basin in central and coastal North Carolina is contaminated with high levels of per- and polyfluoroalkyl substances (PFAS). Elevated levels of PFAS have also been found in blood of fish and wildlife from the Cape Fear River, and in the blood of human populations reliant on contaminated well or surface water from the Cape Fear River basin as a source of drinking water. While the public and environmental health impacts of long-term PFAS exposures are poorly understood, elevated blood concentrations of some PFAS are linked with immunotoxicity and increased incidence of some chronic autoimmune diseases in human populations. The goal of this One Environmental Health study was to evaluate PFAS exposure and biomarkers related to immune health in populations of American alligators (Alligator mississippiensis), a protected and predictive sentinel species of adverse effects caused by persistent toxic pollutants. We found that serum PFAS concentrations in alligator populations from the Cape Fear River were increased compared to a reference population of alligators from the adjoining Lumber River basin. The elevated serum PFAS concentrations in the Cape Fear River alligators were associated with increased innate immune activities, and autoimmune-like phenotypes in this population. In addition to evidence of significantly higher double stranded-DNA binding autoantibodies in adult Cape Fear River alligators, our qRT-PCR analysis found remarkably high induction of Interferon-α signature genes implicated in the pathology of human autoimmune disease. We interpret the association of increased PFAS exposure with disrupted immune functions to suggest that PFAS broadly alters immune activities resulting in autoimmune-like pathology in American alligators. This work substantiates and extends evidence from experimental models and human epidemiology studies showing that some PFAS are immune toxicants. DA - 2022/10/20/ PY - 2022/10/20/ DO - 10.3389/ftox.2022.1010185 VL - 4 SP - SN - 2673-3080 UR - http://dx.doi.org/10.3389/ftox.2022.1010185 KW - autoantibodies KW - autoimmune KW - crocodilian KW - immune toxicity KW - lupus KW - one health KW - PFAS ER - TY - JOUR TI - Interrogating the Metabolomic Profile of Amyotrophic Lateral Sclerosis in the Post-Mortem Human Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry Imaging (MSI) AU - Sohn, Alexandria L. AU - Ping, Lingyan AU - Glass, Jonathan D. AU - Seyfried, Nicholas T. AU - Hector, Emily C. AU - Muddiman, David C. T2 - METABOLITES AB - Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease characterized by progressive loss of motor function with an average survival time of 2-5 years after diagnosis. Due to the lack of signature biomarkers and heterogenous disease phenotypes, a definitive diagnosis of ALS can be challenging. Comprehensive investigation of this disease is imperative to discovering unique features to expedite the diagnostic process and improve diagnostic accuracy. Here, we present untargeted metabolomics by mass spectrometry imaging (MSI) for comparing sporadic ALS (sALS) and C9orf72 positive (C9Pos) post-mortem frontal cortex human brain tissues against a control cohort. The spatial distribution and relative abundance of metabolites were measured by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI for association to biological pathways. Proteomic studies on the same patients were completed via LC-MS/MS in a previous study, and results were integrated with imaging metabolomics results to enhance the breadth of molecular coverage. Utilizing METASPACE annotation platform and MSiPeakfinder, nearly 300 metabolites were identified across the sixteen samples, where 25 were identified as dysregulated between disease cohorts. The dysregulated metabolites were further examined for their relevance to alanine, aspartate, and glutamate metabolism, glutathione metabolism, and arginine and proline metabolism. The dysregulated pathways discussed are consistent with reports from other ALS studies. To our knowledge, this work is the first of its kind, reporting on the investigation of ALS post-mortem human brain tissue analyzed by multiomic MSI. DA - 2022/11// PY - 2022/11// DO - 10.3390/metabo12111096 VL - 12 IS - 11 SP - SN - 2218-1989 KW - IR-MALDESI MSI KW - mass spectrometry imaging KW - Amyotrophic lateral sclerosis (ALS) KW - neurodegenerative disease KW - multiomic ER - TY - JOUR TI - CCS Predictor 2.0: An Open-Source Jupyter Notebook Tool for Filtering Out False Positives in Metabolomics AU - Rainey, Markace A. AU - Watson, Chandler A. AU - Asef, Carter K. AU - Foster, Makayla R. AU - Baker, Erin S. AU - Fernandez, Facundo M. T2 - ANALYTICAL CHEMISTRY AB - Metabolite annotation continues to be the widely accepted bottleneck in nontargeted metabolomics workflows. Annotation of metabolites typically relies on a combination of high-resolution mass spectrometry (MS) with parent and tandem measurements, isotope cluster evaluations, and Kendrick mass defect (KMD) analysis. Chromatographic retention time matching with standards is often used at the later stages of the process, which can also be followed by metabolite isolation and structure confirmation utilizing nuclear magnetic resonance (NMR) spectroscopy. The measurement of gas-phase collision cross-section (CCS) values by ion mobility (IM) spectrometry also adds an important dimension to this workflow by generating an additional molecular parameter that can be used for filtering unlikely structures. The millisecond timescale of IM spectrometry allows the rapid measurement of CCS values and allows easy pairing with existing MS workflows. Here, we report on a highly accurate machine learning algorithm (CCSP 2.0) in an open-source Jupyter Notebook format to predict CCS values based on linear support vector regression models. This tool allows customization of the training set to the needs of the user, enabling the production of models for new adducts or previously unexplored molecular classes. CCSP produces predictions with accuracy equal to or greater than existing machine learning approaches such as CCSbase, DeepCCS, and AllCCS, while being better aligned with FAIR (Findable, Accessible, Interoperable, and Reusable) data principles. Another unique aspect of CCSP 2.0 is its inclusion of a large library of 1613 molecular descriptors via the Mordred Python package, further encoding the fine aspects of isomeric molecular structures. CCS prediction accuracy was tested using CCS values in the McLean CCS Compendium with median relative errors of 1.25, 1.73, and 1.87% for the 170 [M - H]-, 155 [M + H]+, and 138 [M + Na]+ adducts tested. For superclass-matched data sets, CCS predictions via CCSP allowed filtering of 36.1% of incorrect structures while retaining a total of 100% of the correct annotations using a ΔCCS threshold of 2.8% and a mass error of 10 ppm. DA - 2022/12/6/ PY - 2022/12/6/ DO - 10.1021/acs.analchem.2c03491 VL - 12 SP - SN - 1520-6882 ER - TY - JOUR TI - A chromosome level genome assembly of longnose gar,Lepisosteus osseus AU - Mallik, Rittika AU - Carlson, Kara B. AU - Wcisel, Dustin J. AU - Fisk, Michael AU - Yoder, Jeffrey A. AU - Dornburg, Alex AB - Abstract Holosteans (gars and bowfins) represent the sister lineage to teleost fishes, the latter being a clade that comprises over half of all living vertebrates and includes important models for comparative genomics and human health. A major distinction between the evolutionary history of teleosts and holosteans is that all teleosts experienced a genome duplication event in their early evolutionary history. As holostean genomes did not undergo a round of genome duplication, they have been heralded as a means to bridge teleost models to other vertebrate genomes. However, only three species of holosteans have been genome sequenced to date and sequencing of more species is needed to fill sequence sampling gaps and provide a broader comparative basis for understanding holostean genome evolution. Here we report the first high quality reference genome assembly and annotation of the longnose gar ( Lepisosteus osseus ). Our final assembly consists of 22,709 scaffolds with a total length of 945 bp with contig N 50 of 116.6 kb. Using BRAKER2, we annotated a total of 30,068 genes. Analysis of the repetitive regions of the genome reveals the genome to contain 29.1% transposable elements, and the longnose gar to be the only other known vertebrate outside of the spotted gar to contain CR1, L2, Rex1, and Babar. These results highlight the potential utility of holostean genomes for understanding the evolution of vertebrate repetitive elements and provide a critical reference for comparative genomic studies utilizing ray-finned fish models. Significance Over half of all living vertebrates are teleost fishes, including numerous experimental models such as zebrafish ( Danio rerio ) and medaka ( Oryzias latipes ). However, translating research in teleost models to other organisms such as humans is often challenged by the fact that teleosts experienced a genome duplication event in their early evolutionary history. Recent genome sequencing of three holosteans, the sister lineage to teleosts that did not experience a genome duplication event, has revealed these taxa to be critical for linking homologs between teleosts and other vertebrates. Sequencing of holostean genomes remains limited, thereby impeding further comparative genomic studies. Here we fill this sampling gap through the genomic sequencing of the longnose gar ( Lepisosteus osseus ). This annotated reference genome will provide a useful resource for a range of comparative genomic applications that span fields as diverse as immunogenetics, developmental biology, and the understanding of regulatory sequence evolution. DA - 2022/12/22/ PY - 2022/12/22/ DO - 10.1101/2022.12.21.521478 UR - https://doi.org/10.1101/2022.12.21.521478 ER - TY - JOUR TI - TCDD alters essential transcriptional regulators of osteogenic differentiation in multipotent mesenchymal stem cells AU - Watson, AtLee T. D. AU - Carmona Baez, Aldo AU - Jima, Dereje AU - Reif, David AU - Ding, Jun AU - Roberts, Reade AU - Kullman, Seth W. T2 - TOXICOLOGICAL SCIENCES AB - Differentiation of multipotent mesenchymal stem cells (MSCs) into bone-forming osteoblasts requires strict coordination of transcriptional pathways. Aryl hydrocarbon receptor ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), have been shown to alter osteoblast differentiation in vitro and bone formation in multiple developmental in vivo models. The goal of the present study was to establish a global transcriptomic landscape during early, intermediate, and apical stages of osteogenic differentiation in vitro in response to TCDD exposure. Human bone-derived mesenchymal stem cells (hBMSCs) were cultured in growth media (GM), osteogenic differentiation media (ODM), or ODM containing 10 nM TCDD (ODM + TCDD), thus enabling a comparison of the transcriptomic profiles of undifferentiated, differentiated, and differentiated-TCDD-exposed hBMSCs, respectively. In this test system, exposure to TCDD attenuated the differentiation of hBMSCs into osteoblasts as evidenced by reduced alkaline phosphatase activity and mineralization. At various timepoints, we observed altered expression of genes that play a role in the Wnt, fibroblast growth factor, bone morphogenetic protein/transforming growth factor beta developmental pathways, as well as pathways related to extracellular matrix organization and deposition. Reconstruction of gene regulatory networks with the interactive dynamic regulatory event miner (iDREM) analysis revealed modulation of transcription factors (TFs) including POLR3G, NR4A1, RDBP, GTF2B, POU2F2, and ZEB1, which may putatively influence osteoblast differentiation and the requisite deposition and mineralization of bone extracellular matrix. We demonstrate that the combination of RNA-Seq data in conjunction with the iDREM regulatory model captures the transcriptional dynamics underlying MSC differentiation under different conditions in vitro. Model predictions are consistent with existing knowledge and provide a new tool to identify novel pathways and TFs that may facilitate a better understanding of the osteoblast differentiation process, perturbation by exogenous agents, and potential intervention strategies targeting those specific pathways. DA - 2022/11/12/ PY - 2022/11/12/ DO - 10.1093/toxsci/kfac120 VL - 11 SP - SN - 1096-0929 KW - mesenchymal stem cell KW - AhR KW - cell differentiation ER - TY - JOUR TI - Utilizing a Population-Genetic Framework to Test for Gene-Environment Interactions between Zebrafish Behavior and Chemical Exposure AU - Thunga, Preethi AU - Truong, Lisa AU - Rericha, Yvonne AU - Du, Jane La AU - Morshead, Mackenzie AU - Tanguay, Robyn L. AU - Reif, David M. T2 - TOXICS AB - Individuals within genetically diverse populations display broad susceptibility differences upon chemical exposures. Understanding the role of gene-environment interactions (GxE) in differential susceptibility to an expanding exposome is key to protecting public health. However, a chemical's potential to elicit GxE is often not considered during risk assessment. Previously, we've leveraged high-throughput zebrafish (Danio rerio) morphology screening data to reveal patterns of potential GxE effects. Here, using a population genetics framework, we apportioned variation in larval behavior and gene expression in three different PFHxA environments via mixed-effect modeling to assess significance of GxE term. We estimated the intraclass correlation (ICC) between full siblings from different families using one-way random-effects model. We found a significant GxE effect upon PFHxA exposure in larval behavior, and the ICC of behavioral responses in the PFHxA exposed population at the lower concentration was 43.7%, while that of the control population was 14.6%. Considering global gene expression data, a total of 3746 genes showed statistically significant GxE. By showing evidence that heritable genetics are directly affecting gene expression and behavioral susceptibility of individuals to PFHxA exposure, we demonstrate how standing genetic variation in a heterogeneous population such as ours can be leveraged to test for potential GxE. DA - 2022/12// PY - 2022/12// DO - 10.3390/toxics10120769 VL - 10 IS - 12 SP - SN - 2305-6304 UR - https://doi.org/10.3390/toxics10120769 KW - gene-environment interaction KW - chemical risk-assessment KW - zebrafish behavior KW - toxicity screening ER - TY - JOUR TI - Influence of Inoculum Type on Volatile Fatty Acid and Methane Production in Short-Term Anaerobic Food Waste Digestion Tests AU - Ding, Hezhou AU - Barlaz, Morton A. AU - de los Reyes III, Francis L. AU - Call, Douglas F. T2 - ACS SUSTAINABLE CHEMISTRY & ENGINEERING AB - The anaerobic digestion of food waste can yield valuable volatile fatty acids (VFAs), especially when methane (CH4) production is inhibited. Selecting an inoculum with lower methanogenic populations may help reduce CH4 production and improve VFA accumulation. In this study, we investigated VFA and CH4 production in short-term anaerobic batch bioreactors as a function of three inocula compositions derived from a full-scale wastewater treatment facility: (1) anaerobic sludge (AnS), (2) thickened waste activated sludge (TWAS), and (3) TWAS with AnS. The highest VFA concentration (6.62 ± 0.08 g/L) and the lowest total CH4 volume (296 mL) were measured with TWAS only. In contrast, the highest CH4 volume (625 ± 3 mL) was measured in the TWAS + AnS, likely because the AnS was well adapted to digesting TWAS. 16S rDNA sequencing showed that TWAS alone had the lowest relative abundance of methanogens at the start and end of the incubations. The addition of TWAS significantly changed the initial community diversity. These insights suggest that TWAS improves VFA accumulation by providing a microbial community that is more diverse and lower in methanogen abundance relative to AnS. These findings will help guide the selection of inoculation strategies that promote VFA accumulation in anaerobic digesters. DA - 2022/12/9/ PY - 2022/12/9/ DO - 10.1021/acssuschemeng.2c04080 VL - 12 SP - SN - 2168-0485 UR - https://doi.org/10.1021/acssuschemeng.2c04080 KW - anaerobic digestion KW - food waste KW - volatile fatty acids KW - microbial communities KW - methanogenesis ER - TY - JOUR TI - The acclimatory response of the mayfly Neocloeon triangulifer to dilute conditions is linked to the plasticity of sodium transport AU - Cochran, Jamie K. K. AU - Buchwalter, David B. B. T2 - PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES AB - Relative to a growing body of knowledge about the negative consequences of freshwater salinization, little is known about how aquatic insects respond to progressively ion-poor conditions. Here, we examined life-history and physiological acclimation in Neocloeon triangulifer by rearing nymphs from 1-day post-egg hatch to adulthood across a gradient of decreasing Na concentrations (15, 8, 4, 2 and 1 mg l −1 Na). We found no significant changes in survival, growth, development time and whole-body Na content across these treatments. Radiotracer data revealed that nymphs acclimated to their dilute exposures by increasing their rates of Na uptake and were able to maintain a relatively narrow range of uptake rates (±s.e.m.) of 38.5 ± 4.2 µg Na g −1 h −1 across all treatments. By contrast, the Na uptake rates observed in naive nymphs were much more concentration dependent. This acclimatory response is partially explained by differences in ionocyte counts on the gills of nymphs reared under different salinities. Acclimated nymphs were surprisingly less retentive of their sodium composition when subjected to deionized water challenge. By contrasting our findings with a previous N. triangulifer salinity acclimation study, we show a physiological affinity for dilute conditions in this emerging mayfly model. DA - 2022/7/27/ PY - 2022/7/27/ DO - 10.1098/rspb.2022.0529 VL - 289 IS - 1979 SP - SN - 1471-2954 KW - mayfly KW - dilute KW - ion transport KW - acclimation KW - life history KW - sodium ER - TY - JOUR TI - Placing human gene families into their evolutionary context AU - Dornburg, Alex AU - Mallik, Rittika AU - Wang, Zheng AU - Bernal, Moises A. AU - Thompson, Brian AU - Bruford, Elspeth A. AU - Nebert, Daniel W. AU - Vasiliou, Vasilis AU - Yohe, Laurel R. AU - Yoder, Jeffrey A. AU - Townsend, Jeffrey P. T2 - HUMAN GENOMICS AB - Following the draft sequence of the first human genome over 20 years ago, we have achieved unprecedented insights into the rules governing its evolution, often with direct translational relevance to specific diseases. However, staggering sequence complexity has also challenged the development of a more comprehensive understanding of human genome biology. In this context, interspecific genomic studies between humans and other animals have played a critical role in our efforts to decode human gene families. In this review, we focus on how the rapid surge of genome sequencing of both model and non-model organisms now provides a broader comparative framework poised to empower novel discoveries. We begin with a general overview of how comparative approaches are essential for understanding gene family evolution in the human genome, followed by a discussion of analyses of gene expression. We show how homology can provide insights into the genes and gene families associated with immune response, cancer biology, vision, chemosensation, and metabolism, by revealing similarity in processes among distant species. We then explain methodological tools that provide critical advances and show the limitations of common approaches. We conclude with a discussion of how these investigations position us to gain fundamental insights into the evolution of gene families among living organisms in general. We hope that our review catalyzes additional excitement and research on the emerging field of comparative genomics, while aiding the placement of the human genome into its existentially evolutionary context. DA - 2022/11/11/ PY - 2022/11/11/ DO - 10.1186/s40246-022-00429-5 VL - 16 IS - 1 SP - SN - 1479-7364 ER - TY - JOUR TI - Tools for Understanding and Predicting the Affinity of Per- and Polyfluoroalkyl Substances for Anion-Exchange Sorbents br AU - Parker, Bethany A. AU - Knappe, Detlef R. U. AU - Titaley, Ivan A. AU - Wanzek, Thomas A. AU - Field, Jennifer A. T2 - ENVIRONMENTAL SCIENCE & TECHNOLOGY AB - Anion-exchange (AE) sorbents are gaining in popularity for the remediation of anionic per- and polyfluoroalkyl substances (PFAS) in water. However, it is unclear how hydrophobic and electrostatic interactions contribute to anionic PFAS retention. The goal of this study was to understand the effects of PFAS chain length and head group on electrostatic interactions between PFAS and an aminopropyl AE phase. Liquid chromatography-mass spectrometry (LC-MS) was used with an aminopropyl AE guard column to find relative retention times. The average electrostatic potential (EPavg) of each PFAS was calculated, which correlated positively with the PFAS chromatographic retention time, demonstrating the value of EPavg as a proxy for predicting electrostatic interactions between PFAS and the aminopropyl AE phase. The order of greatest to lowest PFAS AE affinity for an aminopropyl column based on chromatographic retention times and electrostatic interactions was n:3 fluorotelomer carboxylic acids (n:3 FtAs) > n:2 fluorotelomer carboxylic acids (n:2 FtAs) > perfluoroalkyl carboxylates (PFCAs) > perfluoroalkyl sulfonamides (FASAs) ∼ n:2 fluorotelomer sulfonates (n:2 FtSs) > perfluoroalkyl sulfonates (PFSAs). This study introduces a methodology for qualitatively characterizing electrostatic interactions between PFAS and AE phases and highlights that electrostatic interactions alone cannot explain the affinity of PFAS for AE resins in water treatment/remediation scenarios. DA - 2022/11/15/ PY - 2022/11/15/ DO - 10.1021/acs.est.1c08345 VL - 56 IS - 22 SP - 15470-15477 SN - 1520-5851 UR - https://doi.org/10.1021/acs.est.1c08345 KW - per-and polyfluoroalkyl substances KW - anion exchange KW - electrostatic potential KW - liquid chromatography ER - TY - JOUR TI - Assessing the Fate of Dissolved Organic Compounds in Landfill Leachate and Wastewater Treatment Systems AU - Doyle, Michael G. AU - Odenkirk, Melanie T. AU - Stewart, Allison K. AU - Nelson, Jacob P. AU - Baker, Erin S. AU - Cruz, Florentino T2 - ACS ES&T WATER AB - Landfill leachate and municipal wastewater are major sources of chemical pollutants that contaminate our drinking water sources. Evaluating the dissolved organic chemical composition in wastewater treatment plants is therefore essential to understand how the discharge impacts the environment, wildlife, and human health. In this study, we utilized a nontargeted analysis method coupling liquid chromatography and tandem mass spectrometry (LC-MS/MS) to analyze chemical features at different points along two landfill leachate treatment plants (LLTPs) and two municipal wastewater treatment plants (WWTPs) in the Southeastern United States. Significant feature differences were observed for the WWTPs where activated sludge clarification was employed versus the LLTPs utilizing reverse osmosis. Specifically, even though both LLTPs had the largest number of features in their influent water, their effluent following reverse osmosis yielded a lower number of features than the WWTPs. Additionally, the clarification processes of each WWTP exhibited different efficiencies as chemical disinfection removed more features than UV disinfection. Feature identification was then made using the LC, MS, and MS/MS information. Analysis of the identified molecules showed that lipids were the most effectively removed from all plants, while alkaloid and organic nitrogen compounds were the most recalcitrant. DA - 2022/11/1/ PY - 2022/11/1/ DO - 10.1021/acsestwater.2c00320 VL - 11 SP - SN - 2690-0637 KW - nontargeted analysis KW - anthropogenic chemicals KW - wastewater KW - landfill leachate KW - reverse osmosis ER - TY - JOUR TI - The imprinted gene Zac1 regulates steatosis in developmental cadmium-induced nonalcoholic fatty liver disease AU - Riegl, Sierra D. AU - Starnes, Cassie AU - Jima, Dereje D. AU - Baptissart, Marine AU - Diehl, Anna Mae AU - Belcher, Scott M. AU - Cowley, Michael T2 - TOXICOLOGICAL SCIENCES AB - Cadmium (Cd) exposure in adulthood is associated with nonalcoholic fatty liver disease (NAFLD), characterized by steatosis, inflammation, and fibrosis. The prevalence of NAFLD in children is increasing, suggesting a role for the developmental environment in programming susceptibility. However, the role of developmental Cd exposure in programming NAFLD and the underlying mechanisms remain unclear. We have proposed that imprinted genes are strong candidates for connecting the early life environment and later life disease. In support of this, we previously identified roles for the Imprinted Gene Network (IGN) and its regulator Zac1 in programming NAFLD in response to maternal metabolic dysfunction. Here, we test the hypothesis that developmental Cd exposure is sufficient to program NAFLD, and further, that this process is mediated by Zac1 and the IGN. Using mice, we show that developmental cadmium chloride (CdCl2) exposure leads to histological, biochemical, and molecular signatures of steatosis and fibrosis in juveniles. Transcriptomic analyses comparing livers of CdCl2-exposed and control mice show upregulation of Zac1 and the IGN coincident with disease presentation. Increased hepatic Zac1 expression is independent of promoter methylation and imprinting statuses. Finally, we show that over-expression of Zac1 in cultured hepatocytes is sufficient to induce lipid accumulation in a Pparγ-dependent manner and demonstrate direct binding of Zac1 to the Pparγ promoter. Our findings demonstrate that developmental Cd exposure is sufficient to program NAFLD in later life, and with our previous work, establish Zac1 and the IGN as key regulators of prosteatotic and profibrotic pathways, two of the major pathological hallmarks of NAFLD. DA - 2022/10/6/ PY - 2022/10/6/ DO - 10.1093/toxsci/kfac106 VL - 10 SP - SN - 1096-0929 KW - nonalcoholic fatty liver disease KW - developmental toxicology KW - epigenetics KW - cadmium KW - genomic imprinting KW - developmental programming ER - TY - JOUR TI - Improved spatial resolution of infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging using a reflective objective AU - Joignant, Alena N. AU - Bai, Hongxia AU - Manni, Jeffrey G., Sr. AU - Muddiman, David C. T2 - RAPID COMMUNICATIONS IN MASS SPECTROMETRY AB - Rationale The level of visual detail of a mass spectrometry image is dependent on the spatial resolution with which it is acquired, which is largely determined by the focal diameter in infrared laser ablation‐based techniques. While the use of mid‐IR light for mass spectrometry imaging (MSI) has advantages, it results in a relatively large focal diameter and spatial resolution. The continual advancement of infrared matrix‐assisted electrospray ionization (IR‐MALDESI) for MSI warranted novel methods to decrease laser ablation areas and thus improve spatial resolution. Methods In this work, a Schwarzschild‐like reflective objective was incorporated into the novel NextGen IR‐MALDESI source and characterized on both burn paper and mammalian tissue using an ice matrix. Ablation areas, mass spectra, and annotations obtained using the objective were compared against the current optical train on the NextGen system without modification. Results The effective resolution was determined to be 55 μm by decreasing the step size until oversampling was observed. Use of the objective improved the spatial resolution by a factor of three as compared against the focus lens. Conclusions A Schwarzschild‐like reflective objective was successfully incorporated into the NextGen source and characterized on mammalian tissue using an ice matrix. The corresponding improvement in spatial resolution facilitates the future expansion of IR‐MALDESI applications to include those that require fine structural detail. DA - 2022/12/15/ PY - 2022/12/15/ DO - 10.1002/rcm.9392 VL - 36 IS - 23 SP - SN - 1097-0231 ER - TY - JOUR TI - Impact of ozone-biologically active filtration on the breakthrough of Perfluoroalkyl acids during granular activated carbon treatment of municipal wastewater effluent AU - Vatankhah, Hooman AU - Tajdini, Bahareh AU - Milstead, Reid P. AU - Clevenger, Erica AU - Murray, Conner AU - Knappe, Detlef AU - Remucal, Christina K. AU - Bellona, Christopher T2 - WATER RESEARCH AB - The presence of perfluoroalkyl acids (PFAAs) in municipal wastewater has highlighted the need to develop PFAA treatment approaches for wastewater effluent and potable reuse applications. Ozone (O3) and biologically active filtration (BAF) were investigated as standalone and combined pretreatment processes to improve the performance of granular activated carbon (GAC) for PFAA removal from wastewater effluent. As individual processes, ozonation at all three investigated doses (0.35, 0.75, 1.0 mg O3/mg DOC) and BAF at both tested empty bed contact times (EBCT; 15 and 20 min) led to significant improvement in PFAA removal by subsequent GAC treatment. With respect to standalone ozonation, the specific O3 dose of 0.75 mg O3/mg DOC was proven to be the optimum operating condition as further increase of the specific ozone dose to 1.0 mg O3/mg DOC did not provide considerable additional improvement. Extending the EBCT during standalone BAF from 15 to 20 minutes significantly improved the efficacy of GAC for the removal of tested PFAAs. Pretreatment with O3-BAF (0.75 mg O3/mg DOC; 20 min EBCT) in tandem outperformed both standalone ozonation and BAF for the removal of PFAA by GAC. Characterization of effluent organic matter (EfOM) by size exclusion chromatography (SEC) and Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR-MS) before and after pretreatments suggest that among multiple co-occurring phenomena, the shift towards smaller and more polar EfOM may have predominantly alleviated pore constriction/blockage without having adverse impact on direct site competition. This observation is supported by SEC and FT-ICR-MS results indicating reduced EfOM molecular size through O3 and BAF pretreatment as well as transition to more hydrophilic byproducts. DA - 2022/9/1/ PY - 2022/9/1/ DO - 10.1016/j.watres.2022.118988 VL - 223 SP - SN - 1879-2448 UR - https://doi.org/10.1016/j.watres.2022.118988 KW - Perfluoroalkyl acids KW - Municipal wastewater effluent KW - Ozonation KW - Biologically active filtration KW - Effluent organic matter KW - Potable reuse ER - TY - JOUR TI - Next-Generation Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Source for Mass Spectrometry Imaging and High-Throughput Screening AU - Knizner, Kevan T. AU - Guymon, Jacob P. AU - Garrard, Kenneth P. AU - Bouvree, Guy AU - Manni, Jeffrey AU - Hauschild, Jan-Peter AU - Strupat, Kerstin AU - Fort, Kyle L. AU - Earley, Lee AU - Wouters, Eloy R. AU - Pu, Fan AU - Radosevich, Andrew J. AU - Elsen, Nathaniel L. AU - Williams, Jon D. AU - Pankow, Mark R. AU - Muddiman, David C. T2 - JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY AB - Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is a hybrid, ambient ionization source that combines the advantages of electrospray ionization and matrix-assisted laser desorption/ionization, making it a versatile tool for both high-throughput screening (HTS) and mass spectrometry imaging (MSI) studies. To expand the capabilities of the IR-MALDESI source, an entirely new architecture was designed to overcome the key limitations of the previous source. This next-generation (NextGen) IR-MALDESI source features a vertically mounted IR-laser, a planar translation stage with computerized sample height control, an aluminum enclosure, and a novel mass spectrometer interface plate. The NextGen IR-MALDESI source has improved user-friendliness, improved overall versatility, and can be coupled to numerous Orbitrap mass spectrometers to accommodate more research laboratories. In this work, we highlight the benefits of the NextGen IR-MALDESI source as an improved platform for MSI and direct analysis. We also optimize the NextGen MALDESI source component geometries to increase target ion abundances over a wide m/z range. Finally, documentation is provided for each NextGen IR-MALDESI part so that it can be replicated and incorporated into any lab space. DA - 2022/9/29/ PY - 2022/9/29/ DO - 10.1021/jasms.2c00178 VL - 9 SP - SN - 1879-1123 KW - IR-MALDESI KW - High-Throughput Screening KW - Mass Spectrometry Imaging KW - Orbitrap Mass Spectrometer KW - Design of Experiments ER - TY - JOUR TI - Comparative Toxicogenomics Database (CTD): update 2023 AU - Davis, Allan Peter AU - Wiegers, Thomas C. AU - Johnson, Robin J. AU - Sciaky, Daniela AU - Wiegers, Jolene AU - Mattingly, Carolyn J. T2 - NUCLEIC ACIDS RESEARCH AB - Abstract The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) harmonizes cross-species heterogeneous data for chemical exposures and their biological repercussions by manually curating and interrelating chemical, gene, phenotype, anatomy, disease, taxa, and exposure content from the published literature. This curated information is integrated to generate inferences, providing potential molecular mediators to develop testable hypotheses and fill in knowledge gaps for environmental health. This dual nature, acting as both a knowledgebase and a discoverybase, makes CTD a unique resource for the scientific community. Here, we report a 20% increase in overall CTD content for 17 100 chemicals, 54 300 genes, 6100 phenotypes, 7270 diseases and 202 000 exposure statements. We also present CTD Tetramers, a novel tool that computationally generates four-unit information blocks connecting a chemical, gene, phenotype, and disease to construct potential molecular mechanistic pathways. Finally, we integrate terms for human biological media used in the CTD Exposure module to corresponding CTD Anatomy pages, allowing users to survey the chemical profiles for any tissue-of-interest and see how these environmental biomarkers are related to phenotypes for any anatomical site. These, and other webpage visual enhancements, continue to promote CTD as a practical, user-friendly, and innovative resource for finding information and generating testable hypotheses about environmental health. DA - 2022/9/28/ PY - 2022/9/28/ DO - 10.1093/nar/gkac833 VL - 9 SP - SN - 1362-4962 ER - TY - JOUR TI - Wildfires and extracellular vesicles: Exosomal MicroRNAs as mediators of cross-tissue cardiopulmonary responses to biomass smoke AU - Carberry, Celeste K. AU - Koval, Lauren E. AU - Payton, Alexis AU - Hartwell, Hadley AU - Kim, Yong Ho AU - Smith, Gregory J. AU - Reif, David M. AU - Jaspers, Ilona AU - Gilmour, M. Ian AU - Rager, Julia E. T2 - ENVIRONMENT INTERNATIONAL AB - Wildfires are a threat to public health world-wide that are growing in intensity and prevalence. The biological mechanisms that elicit wildfire-associated toxicity remain largely unknown. The potential involvement of cross-tissue communication via extracellular vesicles (EVs) is a new mechanism that has yet to be evaluated. Female CD-1 mice were exposed to smoke condensate samples collected from the following biomass burn scenarios: flaming peat; smoldering peat; flaming red oak; and smoldering red oak, representing lab-based simulations of wildfire scenarios. Lung tissue, bronchoalveolar lavage fluid (BALF) samples, peripheral blood, and heart tissues were collected 4 and 24 h post-exposure. Exosome-enriched EVs were isolated from plasma, physically characterized, and profiled for microRNA (miRNA) expression. Pathway-level responses in the lung and heart were evaluated through RNA sequencing and pathway analyses. Markers of cardiopulmonary tissue injury and inflammation from BALF samples were significantly altered in response to exposures, with the greatest changes occurring from flaming biomass conditions. Plasma EV miRNAs relevant to cardiovascular disease showed exposure-induced expression alterations, including miR-150, miR-183, miR-223-3p, miR-30b, and miR-378a. Lung and heart mRNAs were identified with differential expression enriched for hypoxia and cell stress-related pathways. Flaming red oak exposure induced the greatest transcriptional response in the heart, a large portion of which were predicted as regulated by plasma EV miRNAs, including miRNAs known to regulate hypoxia-induced cardiovascular injury. Many of these miRNAs had published evidence supporting their transfer across tissues. A follow-up analysis of miR-30b showed that it was increased in expression in the heart of exposed mice in the absence of changes to its precursor molecular, pri-miR-30b, suggesting potential transfer from external sources (e.g., plasma). This study posits a potential mechanism through which wildfire exposures induce cardiopulmonary responses, highlighting the role of circulating plasma EVs in intercellular and systems-level communication between tissues. DA - 2022/9// PY - 2022/9// DO - 10.1016/j.envint.2022.107419 VL - 167 SP - SN - 1873-6750 KW - Exosomes KW - Extracellular vesicles KW - Environmental exposures KW - Mixtures KW - Systems biology KW - Wildfires ER - TY - JOUR TI - A High-Throughput Ion Mobility Spectrometry-Mass Spectrometry Screening Method for Opioid Profiling AU - Butler, Karen E. AU - Baker, Erin S. T2 - JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY AB - In 2017, the United States Department of Health and Human Services declared the widespread misuse and abuse of prescription and illicit opioids an epidemic. However, this epidemic dates back to the 1990s when opioids were extensively prescribed for pain management. Currently, opioids are still recommended for pain management, and given their abuse potential, rapid screening is imperative for patient treatment. Of particular importance is assessing pain management patient compliance, where evaluating drug use is crucial for preventing opioid abuse and potential overdoses. In this work, we utilized drift tube ion mobility spectrometry coupled with mass spectrometry (DTIMS-MS) to develop a rapid screening method for 33 target opioids and opioid urinary metabolites. Collision cross section values were determined for all target molecules using a flow-injection DTIMS-MS method, and clear differentiation of 27 out of the 33 opioids without prior chromatographic separation was observed when utilizing a high resolution demultiplexing screening approach. An automated solid phase extraction (SPE) platform was then coupled to DTIMS-MS for 10 s sample-to-sample analyses. This SPE-IMS-MS approach enabled the rapid screening of urine samples for opioids and presents a major improvement in sample throughput compared to traditional chromatographic analyses coupled with MS, which routinely take several minutes per sample. Overall, this vast reduction in analysis time facilitates a faster turn-around for patient samples, providing great benefits to clinical applications. DA - 2022/9/22/ PY - 2022/9/22/ DO - 10.1021/jasms.2c00186 VL - 9 SP - SN - 1879-1123 ER - TY - JOUR TI - Evaluation of Metabolism of a Defined Pesticide Mixture through Multiple In Vitro Liver Models AU - Valdiviezo, Alan AU - Kato, Yuki AU - Baker, Erin S. AU - Chiu, Weihsueh A. AU - Rusyn, Ivan T2 - TOXICS AB - The evaluation of exposure to multiple contaminants in a mixture presents a number of challenges. For example, the characterization of chemical metabolism in a mixture setting remains a research area with critical knowledge gaps. Studies of chemical metabolism typically utilize suspension cultures of primary human hepatocytes; however, this model is not suitable for studies of more extended exposures and donor-to-donor variability in a metabolic capacity is unavoidable. To address this issue, we utilized several in vitro models based on human-induced pluripotent stem cell (iPSC)-derived hepatocytes (iHep) to characterize the metabolism of an equimolar (1 or 5 µM) mixture of 20 pesticides. We used iHep suspensions and 2D sandwich cultures, and a microphysiological system OrganoPlate® 2-lane 96 (MimetasTM) that also included endothelial cells and THP-1 cell-derived macrophages. When cell culture media were evaluated using gas and liquid chromatography coupled to tandem mass spectrometry methods, we found that the parent molecule concentrations diminished, consistent with metabolic activity. This effect was most pronounced in iHep suspensions with a 1 µM mixture, and was lowest in OrganoPlate® 2-lane 96 for both mixtures. Additionally, we used ion mobility spectrometry-mass spectrometry (IMS-MS) to screen for metabolite formation in these cultures. These analyses revealed the presence of five primary metabolites that allowed for a more comprehensive evaluation of chemical metabolism in vitro. These findings suggest that iHep-based suspension assays maintain higher metabolic activity compared to 2D sandwich and OrganoPlate® 2-lane 96 model. Moreover, this study illustrates that IMS-MS can characterize in vitro metabolite formation following exposure to mixtures of environmental contaminants. DA - 2022/10// PY - 2022/10// DO - 10.3390/toxics10100566 VL - 10 IS - 10 SP - SN - 2305-6304 UR - https://www.mdpi.com/2305-6304/10/10/566 KW - toxicokinetics KW - chemical mixtures KW - defined mixtures KW - human health risk assessment KW - nontargeted analyses KW - microphysiological systems ER - TY - JOUR TI - Developing transmission mode for infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging AU - Joignant, Alena N. AU - Bai, Hongxia AU - Guymon, Jacob P. AU - Garrard, Kenneth P. AU - Pankow, Mark AU - Muddiman, David C. T2 - RAPID COMMUNICATIONS IN MASS SPECTROMETRY AB - The development and characterization of the novel NextGen infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source catalyzed new advancements in IR-MALDESI instrumentation, including the development of a new analysis geometry.A vertically oriented transmission mode (tm)-IR-MALDESI setup was developed and optimized on thawed mouse tissue. In addition, glycerol was introduced as an alternative energy-absorbing matrix for tm-IR-MALDESI because the new geometry does not currently allow for the formation of an ice matrix. The tm geom was evaluated against the optimized standard geometry for the NextGen source in reflection mode (rm).It was found that tm-IR-MALDESI produces comparable results to rm-IR-MALDESI after optimization. The attempt to incorporate glycerol as an alternative matrix provided little improvement to tm-IR-MALDESI ion abundances.This work has successfully demonstrated the adaptation of the NextGen IR-MALDESI source through the feasibility of tm-IR-MALDESI mass spectrometry imaging on mammalian tissue, expanding future biological applications of the method. DA - 2022/11/30/ PY - 2022/11/30/ DO - 10.1002/rcm.9386 VL - 36 IS - 22 SP - SN - 1097-0231 ER - TY - JOUR TI - Impacts of Gestational FireMaster 550 (FM 550) Exposure on the Neonatal Cortex are Sex Specific and Largely Attributable to the Organophosphate Esters AU - Witchey, S. K. AU - Doyle, M. G. AU - Fredenburg, J. D. AU - St Armour, G. AU - Horman, B. AU - Odenkirk, M. T. AU - Aylor, D. L. AU - Baker, E. S. AU - Patisaul, H. B. T2 - NEUROENDOCRINOLOGY AB - Flame retardants (FRs) are common bodily and environmental pollutants, creating concern about their potential toxicity. We and others have found that the commercial mixture FireMaster® 550 (FM 550) or its individual brominated (BFR) and organophosphate ester (OPFR) components are potential developmental neurotoxicants. Using Wistar rats, we previously reported that developmental exposure to FM 550 or its component classes produced sex- and compound-specific effects on adult socioemotional behaviors. The underlying mechanisms driving the behavioral phenotypes are unknown.To further mechanistic understanding, here we conducted transcriptomics in parallel with a novel lipidomics approach using cortical tissues from newborn siblings of the rats in the published behavioral study. Inclusion of lipid composition is significant because it is rarely examined in developmental neurotoxicity studies. Pups were gestationally exposed via oral dosing to the dam to FM 550 or the BFR or OPFR components at environmentally relevant doses.The neonatal cortex was highly sexually dimorphic in lipid and transcriptome composition, and males were more significantly impacted by FR exposure. Multiple adverse modes of action for the BFRs and OPFRs on neurodevelopment were identified, with the OPFRs being more disruptive than the BFRs via multiple mechanisms including dysregulation of mitochondrial function and disruption of cholinergic and glutamatergic systems. Disrupted mitochondrial function by environmental factors has been linked to a higher risk of autism spectrum disorders and neurodegenerative disorders. Impacted lipid classes included ceramides, sphingomyelins, and triacylglycerides. Robust ceramide upregulation in the OPFR females could suggest a heightened risk of brain metabolic disease.This study reveals multiple mechanisms by which the components of a common FR mixture are developmentally neurotoxic and that the OPFRs may be the compounds of greatest concern. DA - 2022/9/8/ PY - 2022/9/8/ DO - 10.1159/000526959 VL - 9 SP - SN - 1423-0194 ER - TY - JOUR TI - PFAS Challenges and Novel Research A Conversation With the Editorial Board of the AWWA Water Science Topical Collection on PFAS Analytics and Treatment AU - Crimi, Michelle AU - Speth, Thomas F. AU - Chowdhury, Zaid K. AU - Dickenson, Eric R. V. AU - Knappe, Detlef R. U. AU - Liu, Jinxia T2 - JOURNAL AWWA AB - Key Takeaways Per‐ and polyfluoroalkyl substances, “forever chemicals” commonly known as PFAS and used in countless products, have become a significant environmental and public health concern. Among especially alarming PFAS issues are their pervasive presence, the low concentrations at which they are found to be hazardous, and the challenges and limitations of remediation. A roundtable interview with water industry experts—guest editors of an AWWA Water Science article collection—presents their candid, comprehensive take on the PFAS picture. DA - 2022/9// PY - 2022/9// DO - 10.1002/awwa.1956 VL - 114 IS - 7 SP - 13-22 SN - 1551-8833 ER - TY - JOUR TI - Stability and Dissociation of Adeno-Associated Viral Capsids by Variable Temperature-Charge Detection-Mass Spectrometry AU - Kostelic, Marius M. AU - Ryan, Jack P. AU - Brown, Levi S. AU - Jackson, Tyler W. AU - Hsieh, Chih-Chieh AU - Zak, Ciara K. AU - Sanders, Henry M. AU - Liu, Yang AU - Chen, Victor Shugui AU - Byrne, Michael AU - Aspinwall, Craig A. AU - Baker, Erin S. AU - Marty, Michael T. T2 - ANALYTICAL CHEMISTRY AB - Adeno-associated viral (AAV) vectors have emerged as gene therapy and vaccine delivery systems. Differential scanning fluorimetry or differential scanning calorimetry is commonly used to measure the thermal stability of AAVs, but these global methods are unable to distinguish the stabilities of different AAV subpopulations in the same sample. To address this challenge, we combined charge detection-mass spectrometry (CD-MS) with a variable temperature (VT) electrospray source that controls the temperature of the solution prior to electrospray. Using VT-CD-MS, we measured the thermal stabilities of empty and filled capsids. We found that filled AAVs ejected their cargo first and formed intermediate empty capsids before completely dissociating. Finally, we observed that pH stress caused a major decrease in thermal stability. This new approach better characterizes the thermal dissociation of AAVs, providing the simultaneous measurement of the stabilities and dissociation pathways of different subpopulations. DA - 2022/8/18/ PY - 2022/8/18/ DO - 10.1021/acs.analchem.2c02378 VL - 8 SP - SN - 1520-6882 ER - TY - JOUR TI - Drinking Water-Associated PFAS and Fluoroethers and Lipid Outcomes in the GenX Exposure Study AU - Rosen, Emma M. AU - Kotlarz, Nadine AU - Knappe, Detlef R. U. AU - Lea, C. Suzanne AU - Collier, David N. AU - Richardson, David B. AU - Hoppin, Jane A. T2 - ENVIRONMENTAL HEALTH PERSPECTIVES AB - Residents of Wilmington, North, Carolina, were exposed to drinking water contaminated by fluoroethers and legacy per- and polyfluoroalkyl substances (PFAS), such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), with fluoroether exposure occurring from 1980 to 2017. PFOA and PFOS have previously been associated with metabolic dysfunction; however, few prior studies have examined associations between other PFAS and lipid levels.We measured the association between serum fluoroether and legacy PFAS levels and various cholesterol outcomes.Participants in the GenX Exposure Study contributed nonfasting blood samples in November 2017 and May 2018 that were analyzed for 20 PFAS (10 legacy, 10 fluoroethers) and serum lipids [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides] and calculated non-HDL cholesterol. We estimated covariate-adjusted associations between quartiles of exposure to each of the PFAS measures (as well as the summed concentrations of legacy PFAS, fluoroethers, and all 10 targeted PFAS) and lipid outcomes by fitting inverse probability of treatment weighted linear regressions.In this cross-sectional study of 326 participants (age range 6-86 y), eight PFAS were detected in >50% of the population. For PFOS and perfluorononanoic acid (PFNA), non-HDL cholesterol was approximately 5mg/dL higher per exposure quartile increase: [PFOS: 4.89; 95% confidence interval (CI): 0.10, 9.68 and PFNA: 5.25 (95% CI: 0.39, 10.1)], whereas total cholesterol was approximately 6mg/dL higher per quartile [PFOS: 5.71 (95% CI: 0.38, 11.0), PFNA: 5.92 (95% CI: 0.19, 11.7)]. In age-stratified analyses, associations were strongest among the oldest participants. Two fluoroethers were associated with higher HDL, whereas other fluoroether compounds were not associated with serum lipid levels.PFNA and PFOS were associated with higher levels of total and non-HDL cholesterol, with associations larger in magnitude among older adults. In the presence of these legacy PFAS, fluoroethers appeared to be associated with HDL but not non-HDL lipid measures. https://doi.org/10.1289/EHP11033. DA - 2022/9// PY - 2022/9// DO - 10.1289/EHP11033 VL - 130 IS - 9 SP - SN - 1552-9924 UR - https://doi.org/10.1289/EHP11033 ER - TY - JOUR TI - An adaptive teosinte mexicana introgression modulates phosphatidylcholine levels and is associated with maize flowering time AU - Barnes, Allison C. AU - Rodriguez-Zapata, Fausto AU - Juarez-Nunez, Karla A. AU - Gates, Daniel J. AU - Janzen, Garrett M. AU - Kur, Andi AU - Wang, Li AU - Jensen, Sarah E. AU - Estevez-Palmas, Juan M. AU - Crow, Taylor M. AU - Kavi, Heli S. AU - Pil, Hannah D. AU - Stokes, Ruthie L. AU - Knizner, Kevan T. AU - Aguilar-Rangel, Maria R. AU - Demesa-Arevalo, Edgar AU - Skopelitis, Tara AU - Perez-Limon, Sergio AU - Stutts, Whitney L. AU - Thompson, Peter AU - Chiu, Yu-Chun AU - Jackson, David AU - Muddiman, David C. AU - Fiehn, Oliver AU - Runcie, Daniel AU - Buckler, Edward S. AU - Ross-Ibarra, Jeffrey AU - Hufford, Matthew B. AU - Sawers, Ruairidh J. H. AU - Rellan-Alvarez, Ruben T2 - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA AB - Native Americans domesticated maize ( Zea mays ssp. mays ) from lowland teosinte parviglumis ( Zea mays ssp. parviglumis) in the warm Mexican southwest and brought it to the highlands of Mexico and South America where it was exposed to lower temperatures that imposed strong selection on flowering time. Phospholipids are important metabolites in plant responses to low-temperature and phosphorus availability and have been suggested to influence flowering time. Here, we combined linkage mapping with genome scans to identify High PhosphatidylCholine 1 ( HPC1 ), a gene that encodes a phospholipase A1 enzyme, as a major driver of phospholipid variation in highland maize. Common garden experiments demonstrated strong genotype-by-environment interactions associated with variation at HPC1, with the highland HPC1 allele leading to higher fitness in highlands, possibly by hastening flowering. The highland maize HPC1 variant resulted in impaired function of the encoded protein due to a polymorphism in a highly conserved sequence. A meta-analysis across HPC1 orthologs indicated a strong association between the identity of the amino acid at this position and optimal growth in prokaryotes. Mutagenesis of HPC1 via genome editing validated its role in regulating phospholipid metabolism. Finally, we showed that the highland HPC1 allele entered cultivated maize by introgression from the wild highland teosinte Zea mays ssp. mexicana and has been maintained in maize breeding lines from the Northern United States, Canada, and Europe. Thus, HPC1 introgressed from teosinte mexicana underlies a large metabolic QTL that modulates phosphatidylcholine levels and has an adaptive effect at least in part via induction of early flowering time. DA - 2022/7/5/ PY - 2022/7/5/ DO - 10.1073/pnas.2100036119 VL - 119 IS - 27 SP - SN - 1091-6490 KW - phospholipid metabolism KW - maize genetics KW - highland adaptation KW - flowering time KW - selection ER - TY - JOUR TI - Introducing the Lipidomics Minimal Reporting Checklist AU - McDonald, Jeffrey G. AU - Ejsing, Christer S. AU - Kopczynski, Dominik AU - Holcapek, Michal AU - Aoki, Junken AU - Arita, Makoto AU - Arita, Masanori AU - Baker, Erin S. AU - Bertrand-Michel, Justine AU - Bowden, John A. AU - Brugger, Britta AU - Ellis, Shane R. AU - Fedorova, Maria AU - Griffiths, William J. AU - Han, Xianlin AU - Hartler, Jurgen AU - Hoffmann, Nils AU - Koelmel, Jeremy P. AU - Kofeler, Harald C. AU - Mitchell, Todd W. AU - Valerie B. O'Donnell, AU - Saigusa, Daisuke AU - Schwudke, Dominik AU - Shevchenko, Andrej AU - Ulmer, Candice Z. AU - Wenk, Markus R. AU - Witting, Michael AU - Wolrab, Denise AU - Xia, Yu AU - Ahrends, Robert AU - Liebisch, Gerhard AU - Ekroos, Kim T2 - NATURE METABOLISM AB - The rapid increase in lipidomic data has triggered a community-based movement to develop guidelines and minimum requirements for generating, reporting and publishing lipidomic data. The creation of a dynamic checklist summarizing key details of lipidomic analyses using a common language has the potential to harmonize the field by improving both traceability and reproducibility. DA - 2022/8/8/ PY - 2022/8/8/ DO - 10.1038/s42255-022-00628-3 VL - 8 SP - SN - 2522-5812 ER - TY - JOUR TI - Allergic and non-allergic wheeze among farm women in the Agricultural Health Study (2005-2010) AU - Islam, Jessica Y. AU - Mohamed, Ahmed AU - Umbach, David M. AU - London, Stephanie J. AU - Henneberger, Paul K. AU - Freeman, Laura E. Beane AU - Sandler, Dale P. AU - Hoppin, Jane A. T2 - OCCUPATIONAL AND ENVIRONMENTAL MEDICINE AB - Farms represent complex environments for respiratory exposures including hays, grains and pesticides. Little is known about the impact of these exposures on women's respiratory health. We evaluated the association of farm exposures with allergic and non-allergic wheeze among women in the Agricultural Health Study, a study of farmers and their spouses based in Iowa and North Carolina.We used self-reported data (2005-2010) on current use (≤12 months) of 15 pesticides (selected based on frequency of use) and occupational farm activities from 20 164 women. We defined allergic wheeze as reporting wheeze and doctor-diagnosed hay fever (7%) and non-allergic wheeze as wheeze but not hay fever (8%) in the past 12 months. Using polytomous logistic regression, we evaluated associations of wheeze subtypes with pesticides and other farm exposures (eg, raising farm animals) using no wheeze/hay fever as the referent, adjusting for age, body mass index, state, current asthma, glyphosate use and smoking.Current use of any pesticide, reported by 7% of women, was associated with both allergic (OR: 1.36, 95% CI: 1.10 to 1.67) and non-allergic (OR: 1.25, 95% CI: 1.04 to 1.51) wheeze. Four pesticides were associated with at least one wheeze subtype: glyphosate, with both wheeze subtypes; diazinon and fly spray with only allergic wheeze; carbaryl with only non-allergic wheeze. Working weekly with mouldy hay was associated with allergic (OR: 1.88, 95% CI: 1.26 to 2.80) and non-allergic wheeze (OR: 1.69, 95% CI: 1.18 to 2.42).Use of specific pesticides and certain farm activities may contribute to wheeze among farm women. DA - 2022/8/8/ PY - 2022/8/8/ DO - 10.1136/oemed-2022-108252 VL - 8 SP - SN - 1470-7926 UR - https://doi.org/10.1136/oemed-2022-108252 KW - Allergy KW - Pesticides KW - Respiratory System ER - TY - JOUR TI - Novel matrix strategies for improved ionization and spatial resolution using IR-MALDESI mass spectrometry imaging AU - Kibbe, Russell R. AU - Mellinger, Allyson L. AU - Muddiman, David C. T2 - JOURNAL OF MASS SPECTROMETRY AB - In mass spectrometry imaging (MSI) applications of infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI), an exogenous ice layer is the gold standard for an energy-absorbing matrix. However, the formation of the ice matrix requires additional time and instrument hardware, so glycerol was investigated herein as an alternative to the ice matrix to potentially improve spatial resolution and ionization, while decreasing experiment time. Glycerol solutions of varying concentrations were sprayed over top of rat liver tissue sections for analysis by IR-MALDESI and compared to the typical ice matrix condition. Additionally, we tested if combining the ice matrix and glycerol matrix would further improve analyses. Matrix conditions were evaluated by comparing ion abundance of six lipid species, the laser ablation spot diameter, and number of METASPACE annotations. The ion abundances were also normalized to the volume of tissue ablated to correct for lower abundance values due to less ablated tissue. It was observed that utilizing a 50% glycerol matrix without ice provides improved spatial resolution with lipid abundances and annotations comparable to the ice matrix standard, while decreasing the time required to complete an IR-MALDESI tissue imaging experiment. DA - 2022/8// PY - 2022/8// DO - 10.1002/jms.4875 VL - 57 IS - 8 SP - SN - 1096-9888 KW - energy-absorbing matrix KW - glycerol KW - IR-MALDESI KW - mass spectrometry imaging ER - TY - JOUR TI - Glycerate from intestinal fructose metabolism induces islet cell damage and glucose intolerance AU - Wu, Yanru AU - Wong, Chi Wut AU - Chiles, Eric N. AU - Mellinger, Allyson L. AU - Bae, Hosung AU - Jung, Sunhee AU - Peterson, Ted AU - Wang, Jamie AU - Negrete, Marcos AU - Huang, Qiang AU - Wang, Lihua AU - Jang, Cholsoon AU - Muddiman, David C. AU - Su, Xiaoyang AU - Williamson, Ian AU - Shen, Xiling T2 - CELL METABOLISM AB - Dietary fructose, especially in the context of a high-fat western diet, has been linked to type 2 diabetes. Although the effect of fructose on liver metabolism has been extensively studied, a significant portion of the fructose is first metabolized in the small intestine. Here, we report that dietary fat enhances intestinal fructose metabolism, which releases glycerate into the blood. Chronic high systemic glycerate levels induce glucose intolerance by slowly damaging pancreatic islet cells and reducing islet sizes. Our findings provide a link between dietary fructose and diabetes that is modulated by dietary fat. DA - 2022/7/5/ PY - 2022/7/5/ DO - 10.1016/j.cmet.2022.05.007 VL - 34 IS - 7 SP - 1042-+ SN - 1932-7420 ER - TY - JOUR TI - Nonylphenol Polyethoxylates Enhance Adipose Deposition in Developmentally Exposed Zebrafish (vol 10, 99, 2022) AU - Kassotis, Christopher D. AU - LeFauve, Matthew K. AU - Chiang, Yu-Ting Tiffany AU - Knuth, Megan M. AU - Schkoda, Stacy AU - Kullman, Seth W. T2 - TOXICS AB - In the original publication [...]. DA - 2022/7// PY - 2022/7// DO - 10.3390/toxics10070345 VL - 10 IS - 7 SP - SN - 2305-6304 ER - TY - JOUR TI - Comparative assessment of blood mercury in American alligators (Alligator mississippiensis) from Coastal North Carolina and Florida AU - Belcher, Scott M. AU - Guillette, Matthew P. AU - Robb, Frank AU - Rock, Kylie D. T2 - ECOTOXICOLOGY AB - Mercury (Hg) is a widespread and harmful persistent pollutant of aquatic ecosystems. Except for the northern most populations of American alligators (Alligator Mississippiensis) found in North Carolina, the potential adverse health impacts of Hg on ecosystems and humans consuming alligator meat have been studied for over three decades. Now that alligators are being recreationally hunted and consumed across their range, it is especially important to monitor toxic contaminant levels to best understand possible adverse impacts of exposures on alligator populations and human health. In this study, we determined blood Hg concentrations in American alligators from an urbanized site in Wilmington, NC, a nearby site at Lake Waccamaw, NC, and a site on the St Johns River in Florida. Median blood total Hg (tHg) concentrations were particularly high at Lake Waccamaw (526 ng/g, range 152–946 ng/g), resulting in median muscle concentrations (0.48 mg/kg, range 0.13–0.88 mg/kg) well above US EPA screening values for fish consumption. Median concentrations at the Wilmington site (69 ng/g, range 22–336 ng/g) were generally low, and Hg concentrations from the St Johns River site (143 ng/g, range 54–244 ng/g) were comparable to those reported in previous studies. Analysis of relationships between tHg concentrations and a panel of blood chemistry biomarkers found only modest concentration-dependent impact on biomarkers of renal function. The results of this study reveal that local environmental factors greatly impact Hg bioaccumulation in alligators, findings that reaffirm local contaminant biomonitoring in alligator populations will be critical for affective management and determination of guidelines for safe consumption of harvested alligators. DA - 2022/8/3/ PY - 2022/8/3/ DO - 10.1007/s10646-022-02573-z VL - 8 SP - SN - 1573-3017 UR - https://doi.org/10.1007/s10646-022-02573-z KW - Bioaccumulation KW - Biomonitoring KW - Ecotoxicology KW - Mercury KW - Metals KW - Reptile ER - TY - JOUR TI - A highly diverse set of novel immunoglobulin-like transcript (NILT) genes in zebrafish indicates a wide range of functions with complex relationships to mammalian receptors AU - Wcisel, Dustin J. AU - Dornburg, Alex AU - McConnell, Sean C. AU - Hernandez, Kyle M. AU - Andrade, Jorge AU - Jong, Jill L. O. AU - Litman, Gary W. AU - Yoder, Jeffrey A. T2 - IMMUNOGENETICS AB - Multiple novel immunoglobulin-like transcripts (NILTs) have been identified from salmon, trout, and carp. NILTs typically encode activating or inhibitory transmembrane receptors with extracellular immunoglobulin (Ig) domains. Although predicted to provide immune recognition in ray-finned fish, we currently lack a definitive framework of NILT diversity, thereby limiting our predictions for their evolutionary origin and function. In order to better understand the diversity of NILTs and their possible roles in immune function, we identified five NILT loci in the Atlantic salmon (Salmo salar) genome, defined 86 NILT Ig domains within a 3-Mbp region of zebrafish (Danio rerio) chromosome 1, and described 41 NILT Ig domains as part of an alternative haplotype for this same genomic region. We then identified transcripts encoded by 43 different NILT genes which reflect an unprecedented diversity of Ig domain sequences and combinations for a family of non-recombining receptors within a single species. Zebrafish NILTs include a sole putative activating receptor but extensive inhibitory and secreted forms as well as membrane-bound forms with no known signaling motifs. These results reveal a higher level of genetic complexity, interindividual variation, and sequence diversity for NILTs than previously described, suggesting that this gene family likely plays multiple roles in host immunity. DA - 2022/7/23/ PY - 2022/7/23/ DO - 10.1007/s00251-022-01270-9 VL - 7 SP - SN - 1432-1211 KW - Innate immunity KW - Gene content variation KW - Alternative immune haplotypes KW - Gene family evolution KW - Mammalian CD300 (CMRF35) KW - Mammalian NCR2 (NKp44) ER - TY - JOUR TI - Utilizing Skyline to analyze lipidomics data containing liquid chromatography, ion mobility spectrometry and mass spectrometry dimensions AU - Kirkwood, Kaylie I AU - Pratt, Brian S. AU - Shulman, Nicholas AU - Tamura, Kaipo AU - MacCoss, Michael J. AU - MacLean, Brendan X. AU - Baker, Erin S. T2 - NATURE PROTOCOLS AB - Lipidomics studies suffer from analytical and annotation challenges because of the great structural similarity of many of the lipid species. To improve lipid characterization and annotation capabilities beyond those afforded by traditional mass spectrometry (MS)-based methods, multidimensional separation methods such as those integrating liquid chromatography, ion mobility spectrometry, collision-induced dissociation and MS (LC-IMS-CID-MS) may be used. Although LC-IMS-CID-MS and other multidimensional methods offer valuable hydrophobicity, structural and mass information, the files are also complex and difficult to assess. Thus, the development of software tools to rapidly process and facilitate confident lipid annotations is essential. In this Protocol Extension, we use the freely available, vendor-neutral and open-source software Skyline to process and annotate multidimensional lipidomic data. Although Skyline ( https://skyline.ms/skyline.url ) was established for targeted processing of LC-MS-based proteomics data, it has since been extended such that it can be used to analyze small-molecule data as well as data containing the IMS dimension. This protocol uses Skyline's recently expanded capabilities, including small-molecule spectral libraries, indexed retention time and ion mobility filtering, and provides a step-by-step description for importing data, predicting retention times, validating lipid annotations, exporting results and editing our manually validated 500+ lipid library. Although the time required to complete the steps outlined here varies on the basis of multiple factors such as dataset size and familiarity with Skyline, this protocol takes ~5.5 h to complete when annotations are rigorously verified for maximum confidence. DA - 2022/7/13/ PY - 2022/7/13/ DO - 10.1038/s41596-022-00714-6 VL - 7 SP - SN - 1750-2799 ER - TY - JOUR TI - Diffusion of benzene and tetrachloroethylene through saturated cement paste AU - Hosseini, Payam AU - McElroy, Amie AU - Knappe, Detlef R. U. AU - Gabr, Mohammed AU - Pour-Ghaz, Mohammad T2 - CONSTRUCTION AND BUILDING MATERIALS AB - Diffusion of highly volatile organic compounds (VOCs) through buried concrete infrastructure components, such as pipes and culverts, can occur if these components come in contact with contaminated groundwater or soil. Among various VOCs, benzene and tetrachloroethylene (PCE), are the most common contaminants. This paper aims at measuring the effective diffusion coefficients of benzene and PCE in cement paste. The free diffusion coefficients of VOCs in simulated pore solution were also measured and used in empirical models. Results show that VOCs diffusion coefficients decreased with decreasing w/c because of reduced porosity and increased tortuosity of the pore network as well as increased ionic strength of the pore solution. The increased ionic strength of the pore solution reduced the solubility limit of VOCs in the pore solution and decreased the free diffusion coefficient of VOCs in the pore solution. Also, among all models, phenomenological model provided the most accurate estimates. DA - 2022/4/25/ PY - 2022/4/25/ DO - 10.1016/j.conbuildmat.2022.127196 VL - 329 SP - SN - 1879-0526 KW - Volatile organic compounds KW - Cement paste KW - Saturated state KW - Diffusion coefficient KW - Prediction model ER - TY - JOUR TI - Knockdown of Transmembrane Protein 150A (TMEM150A) Results in Increased Production of Multiple Cytokines AU - Romanet, Jessica L. AU - Cupo, Katherine L. AU - Yoder, Jeffrey A. T2 - JOURNAL OF INTERFERON AND CYTOKINE RESEARCH AB - Lipopolysaccharide (LPS)-induced signaling through Toll-like receptor 4 (TLR4) is mediated by the plasma membrane lipid, phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] and its derivatives diacylglycerol and inositol trisphosphate. Levels of PI(4,5)P2 are controlled enzymatically and fluctuate in LPS-stimulated cells. Recently, transmembrane protein 150A (TMEM150A/TM6P1/damage-regulated autophagy modulator 5) has been shown to regulate PI(4,5)P2 production at the plasma membrane by modifying the composition of the phosphatidylinositol 4-kinase enzyme complex. To determine if TMEM150A function impacts TLR4 signaling, TMEM150A was knocked down in TLR4-expressing epithelial cells and cytokine expression quantified after LPS stimulation. In general, decreased expression of TMEM150A led to increased levels of LPS-induced cytokine secretion and transcript levels. Unexpectedly, knockdown of TMEM150A in a lung epithelial cell line (H292) also led to increased cytokine levels in the unstimulated conditions suggesting TMEM150A plays an important role in cellular homeostasis. Future studies will investigate if TMEM150A plays a similar role for other TLR agonists and in other cell lineages. DA - 2022/7/1/ PY - 2022/7/1/ DO - 10.1089/jir.2022.0063 VL - 42 IS - 7 SP - 336-342 SN - 1557-7465 UR - https://doi.org/10.1089/jir.2022.0063 KW - cell signaling KW - interleukin-8 KW - interleukin-6 KW - RANTES KW - TMEM150A KW - TLR4 ER - TY - JOUR TI - Highlighting Functional Mass Spectrometry Imaging Methods in Bioanalysis AU - Mellinger, Allyson L. AU - Muddiman, David C. AU - Gamcsik, Michael P. T2 - JOURNAL OF PROTEOME RESEARCH AB - Most mass spectrometry imaging (MSI) methods provide a molecular map of tissue content but little information on tissue function. Mapping tissue function is possible using several well-known examples of "functional imaging" such as positron emission tomography and functional magnetic resonance imaging that can provide the spatial distribution of time-dependent biological processes. These functional imaging methods represent the net output of molecular networks influenced by local tissue environments that are difficult to predict from molecular/cellular content alone. However, for decades, MSI methods have also been demonstrated to provide functional imaging data on a variety of biological processes. In fact, MSI exceeds some of the classic functional imaging methods, demonstrating the ability to provide functional data from the nanoscale (subcellular) to whole tissue or organ level. This Perspective highlights several examples of how different MSI ionization and detection technologies can provide unprecedented detailed spatial maps of time-dependent biological processes, namely, nucleic acid synthesis, lipid metabolism, bioenergetics, and protein metabolism. By classifying various MSI methods under the umbrella of "functional MSI", we hope to draw attention to both the unique capabilities and accessibility with the aim of expanding this underappreciated field to include new approaches and applications. DA - 2022/6/27/ PY - 2022/6/27/ DO - 10.1021/acs.jproteome.2c00220 VL - 6 SP - SN - 1535-3907 KW - mass spectrometry imaging KW - kinetics KW - rate KW - isotope KW - metabolism KW - dynamics ER - TY - JOUR TI - Genomic map of candidate human imprint control regions: the imprintome AU - Jima, Dereje D. AU - Skaar, David A. AU - Planchart, Antonio AU - Motsinger-Reif, Alison AU - Cevik, Sebnem E. AU - Park, Sarah S. AU - Cowley, Michael AU - Wright, Fred AU - House, John AU - Liu, Andy AU - Jirtle, Randy L. AU - Hoyo, Cathrine T2 - EPIGENETICS AB - 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. DA - 2022/6/25/ PY - 2022/6/25/ DO - 10.1080/15592294.2022.2091815 VL - 6 SP - SN - 1559-2308 KW - Epigenetics KW - genomic imprinting KW - foetal origins KW - whole genome KW - methylation KW - imprint control regions ER - TY - JOUR TI - Pyrimethanil and chlorpyrifos air concentrations and pregnant women's urinary metabolites in the Infants' Environmental Health Study (ISA) Costa Rica , AU - Giffin, Andrew AU - Hoppin, Jane A. AU - Cordoba, Leonel AU - Solano-Diaz, Karla AU - Ruepert, Clemens AU - Penaloza-Castaneda, Jorge AU - Lindh, Christian AU - Reich, Brian J. AU - Joode, Berna van Wendel T2 - ENVIRONMENT INTERNATIONAL AB - Only few studies have compared environmental pesticide air concentrations with specific urinary metabolites to evaluate pathways of exposure. Therefore, we compared pyrimethanil and chlorpyrifos concentrations in air with urinary 4-hydroxypyrimethanil (OHP, metabolite of pyrimethanil) and 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos) among pregnant women from the Infant’s Environmental Health Study (ISA) in Matina County, Costa Rica. During pregnancy, we obtained repeat urinary samples from 448 women enrolled in the ISA study. We extrapolated pyrimethanil and chlorpyrifos concentrations measured with passive air samplers (PAS) (n = 48, from 12 schools), across space and time using a Bayesian spatiotemporal model. We subsequently compared these concentrations with urinary OHP and TCPy in 915 samples from 448 women, using separate mixed models and considering several covariables. A 10% increase in air pyrimethanil (ng/m3) was associated with a 5.7% (95% confidence interval (CI 4.6, 6.8) increase in OHP (μg/L). Women living further from banana plantations had lower OHP: −0.7% (95% CI −1.2, −0.3) for each 10% increase in distance (meters) as well as women who ate rice and beans ≥15 times a week −23% (95% CI −38, −4). In addition, each 1 ng/m3 increase in chlorpyrifos in air was associated with a 1.5% (95% CI 0.2, 2.8) increase in TCPy (μg/L), and women working in agriculture tended to have increased TCPy (21%, 95% CI −2, 49). The Bayesian spatiotemporal models were useful to estimate pyrimethanil and chlorpyrifos air concentrations across space and time. Our results suggest inhalation of pyrimethanil and chlorpyrifos is a pathway of environmental exposure. PAS seems a useful technique to monitor environmental current-use pesticide exposures. For future studies, we recommend increasing the number of locations of environmental air measurements, obtaining all air and urine measurements during the same month, and, ideally, including dermal exposure estimates as well. DA - 2022/8// PY - 2022/8// DO - 10.1016/j.envint.2022.107328 VL - 166 SP - SN - 1873-6750 KW - Urinary pesticide metabolites KW - Airborne pesticide exposure KW - Spatiotemporal model KW - Environmental exposure KW - Pesticides KW - Insecticides KW - Fungicides ER - TY - JOUR TI - Uncovering PFAS and Other Xenobiotics in the Dark Metabolome Using Ion Mobility Spectrometry, Mass Defect Analysis, and Machine Learning AU - Foster, MaKayla AU - Rainey, Markace AU - Watson, Chandler AU - Dodds, James N. AU - Kirkwood, Kaylie I AU - Fernandez, Facundo M. AU - Baker, Erin S. T2 - ENVIRONMENTAL SCIENCE & TECHNOLOGY AB - The identification of xenobiotics in nontargeted metabolomic analyses is a vital step in understanding human exposure. Xenobiotic metabolism, transformation, excretion, and coexistence with other endogenous molecules, however, greatly complicate the interpretation of features detected in nontargeted studies. While mass spectrometry (MS)-based platforms are commonly used in metabolomic measurements, deconvoluting endogenous metabolites from xenobiotics is also often challenged by the lack of xenobiotic parent and metabolite standards as well as the numerous isomers possible for each small molecule m/z feature. Here, we evaluate a xenobiotic structural annotation workflow using ion mobility spectrometry coupled with MS (IMS-MS), mass defect filtering, and machine learning to uncover potential xenobiotic classes and species in large metabolomic feature lists. Xenobiotic classes examined included those of known high toxicities, including per- and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and pesticides. Specifically, when the workflow was applied to identify PFAS in the NIST SRM 1957 and 909c human serum samples, it greatly reduced the hundreds of detected liquid chromatography (LC)-IMS-MS features by utilizing both mass defect filtering and m/z versus IMS collision cross sections relationships. These potential PFAS features were then compared to the EPA CompTox entries, and while some matched within specific m/z tolerances, there were still many unknowns illustrating the importance of nontargeted studies for detecting new molecules with known chemical characteristics. Additionally, this workflow can also be utilized to evaluate other xenobiotics and enable more confident annotations from nontargeted studies. DA - 2022/6/21/ PY - 2022/6/21/ DO - 10.1021/acs.est.2c00201 VL - 56 IS - 12 SP - 9133-9143 SN - 1520-5851 KW - xenobiotics KW - per- and polyfluoroalkyl substances KW - ion mobility spectrometry KW - mass spectrometry KW - mass defect KW - machine learning KW - PFAS ER - TY - JOUR TI - Extraction and Matrix Cleanup Method for Analyzing Novel Per- and Polyfluoroalkyl Ether Acids and Other Per- and Polyfluoroalkyl Substances in Fruits and Vegetables AU - Meng, Pingping AU - DeStefano, Noelle J. AU - Knappe, Detlef R. U. T2 - JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY AB - Per- and polyfluoroalkyl ether acids (PFEAs) are a subclass of per- and polyfluoroalkyl substances (PFAS) that are detected with increasing frequency in environmental matrices. Diet can be an important route of PFEA exposure, but the presence of PFEAs in food is poorly understood. Extraction methods for food samples exist for traditionally studied PFAS, but their suitability for PFEAs and other novel PFAS remains unknown. In this study, an extraction and matrix cleanup method was developed to quantify 45 PFAS, including 13 PFEAs, 3 perfluoroalkane sulfonamides, and 6 fluorotelomer carboxylic acids in 10 types of fruits and vegetables. Homogenized samples were extracted with basic methanol, and resulting extracts were diluted with water and cleaned up using solid-phase extraction with weak anion-exchange cartridges. The method was validated by performing spike-recovery experiments at spike levels of 1 ng/g in all 10 matrices and 0.1 ng/g in 2 matrices. For PFAS without a corresponding isotopically labeled internal standard (IS), adopting an IS with a similar chromatographic retention time generated the most accurate recoveries. Dependent upon the matrix, recoveries of 38-44 PFAS (including 10-13 PFEAs) fell within 50-150% for samples spiked at 1 ng/g. Recoveries of 40 and 38 PFAS in blueberries and corn, respectively, fell within 50-150% for samples spiked at 0.1 ng/g. Method quantification limits (MQLs) of PFAS in pure solvents were determined as the lowest calibration level with an accuracy between 70 and 130%. To compensate for matrix effects, a matrix factor was applied on the basis of the analyte response in different matrices relative to the pure solvent. The MQLs of 45 PFAS (including 13 PFEAs) in 10 matrices ranged from 0.025 to 0.25 ng/g. Overall, this method is capable of sensitively quantifying 45 PFAS in many fruits and vegetables. DA - 2022/4/27/ PY - 2022/4/27/ DO - 10.1021/acs.jafc.1c07665 VL - 70 IS - 16 SP - 4792-4804 SN - 1520-5118 UR - https://doi.org/10.1021/acs.jafc.1c07665 KW - PFEAs KW - PFAS KW - method quantification limits KW - extraction and matrix cleanup method KW - fruits and vegetables ER - TY - JOUR TI - Stability of Per- and Polyfluoroalkyl Substances in Solvents Relevant to Environmental and Toxicological Analysis br AU - Zhang, Chuhui AU - McElroy, Amie C. AU - Liberatore, Hannah K. AU - Alexander, Nancy Lee M. AU - Knappe, Detlef R. U. T2 - ENVIRONMENTAL SCIENCE & TECHNOLOGY AB - Per- and polyfluoroalkyl substances (PFASs) are widely used anthropogenic chemicals. For environmental and toxicological analysis, it is important to understand the stability of PFASs, including novel per- and polyfluoroalkyl ether acids (PFEAs), in commonly used solvents. In this study, we investigated the effects of PFAS characteristics, solvent type, water-to-organic solvent ratio, and temperature on the stability of 21 PFASs including 18 PFEAs. None of the studied PFASs showed measurable degradation in deionized water, methanol, or isopropyl alcohol over 30 days; however, nine PFEAs degraded in the polar aprotic solvents acetonitrile, acetone, and dimethyl sulfoxide (DMSO). PFEA degradation followed first-order kinetics, and first-order rate constants increased with increasing temperature and with decreasing water-to-organic solvent ratio. Monoethers with a carboxylic acid functional group adjacent to a tertiary carbon (>CF-COOH) degraded more rapidly than multiethers in which the carboxylic acid moiety was adjacent to repeating -CF2O- groups. In contrast, monoethers with a carboxylic acid moiety adjacent to a secondary carbon (-CF2-COOH) were stable in all tested solvents. Using high-resolution mass spectrometry, we determined that PFEAs with a >CF-COOH group were stoichiometrically decarboxylated in aprotic solvents and formed products with a >CFH group; e.g., hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX), HFPO-trimer acid, and HFPO-tetramer acid were stoichiometrically converted to Fluoroethers E-1, E-2, and E-3, respectively. PFEA degradation results highlight the importance of solvent choice when preparing dosing solutions and performing extractions for environmental and toxicological assessments of PFEAs. DA - 2022/5/17/ PY - 2022/5/17/ DO - 10.1021/acs.est.1c03979 VL - 56 IS - 10 SP - 6103-6112 SN - 1520-5851 UR - https://doi.org/10.1021/acs.est.1c03979 KW - PFAS KW - fluoroethers KW - GenX KW - acetonitrile KW - acetone KW - dimethyl sulfoxide KW - degradation KW - high-resolution mass spectrometry ER - TY - JOUR TI - Normalization techniques for high-throughput screening by infrared matrix-assisted laser desorption electrospray ionization mass spectrometry AU - Knizner, Kevan T. AU - Bagley, Michael C. AU - Pu, Fan AU - Elsen, Nathaniel L. AU - Williams, Jon D. AU - Muddiman, David C. T2 - JOURNAL OF MASS SPECTROMETRY AB - Mass spectrometry (MS) is an effective analytical tool for high-throughput screening (HTS) in the drug discovery field. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MS is a high-throughput platform that has achieved analysis times of sub-seconds-per-sample. Due to the high-throughput analysis speed, methods are needed to increase the analyte signal while decreasing the variability in IR-MALDESI-MS analyses to improve data quality and reduce false-positive hits. The Z-factor is used as a statistic of assay quality that can be improved by reducing the variation of target ion abundances or increasing signal. Herein we report optimal solvent compositions for increasing measured analyte abundances with direct analysis by IR-MALDESI-MS. We also evaluate normalization strategies, such as adding a normalization standard that is similar or dissimilar in structure to the model target drug, to reduce the variability of measured analyte abundances with direct analyses by IR-MALDESI-MS in both positive and negative ionization modes. DA - 2022/6// PY - 2022/6// DO - 10.1002/jms.4869 VL - 57 IS - 6 SP - SN - 1096-9888 KW - high-throughput screening KW - IR-MALDESI KW - normalization KW - Orbitrap mass spectrometer ER - TY - JOUR TI - Surface Modified Nano-Electrospray Needles Improve Sensitivity for Native Mass Spectrometry AU - Kostelic, Marius M. AU - Hsieh, Chih-Chieh AU - Sanders, Henry M. AU - Zak, Ciara K. AU - Ryan, Jack P. AU - Baker, Erin S. AU - Aspinwall, Craig A. AU - Marty, Michael T. T2 - JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY AB - Native mass spectrometry (MS) and charge detection-mass spectrometry (CD-MS) have become versatile tools for characterizing a wide range of proteins and macromolecular complexes. Both commonly use nanoelectrospray ionization (nESI) from pulled borosilicate needles, but some analytes are known to nonspecifically adsorb to the glass, which may lower sensitivity and limit the quality of the data. To improve the sensitivity of native MS and CD-MS, we modified the surface of nESI needles with inert surface modifiers, including polyethylene-glycol. We found that the surface modification improved the signal intensity for native MS of proteins and for CD-MS of adeno-associated viral capsids. Based on mechanistic comparisons, we hypothesize that the improvement is more likely due to an increased flow rate with coated ESI needles rather than less nonspecific adsorption. In any case, these surface-modified needles provide a simple and inexpensive method for improving the sensitivity of challenging analytes. DA - 2022/6/1/ PY - 2022/6/1/ DO - 10.1021/jasms.2c00087 VL - 33 IS - 6 SP - 1031-1037 SN - 1879-1123 KW - native mass spectrometry KW - charge detection mass spectrometry KW - electrospray ionization KW - silane chemistry ER - TY - JOUR TI - Cupric Ions Selectively Modulate TRAAK-Phosphatidylserine Interactions AU - Zhu, Yun AU - Schrecke, Samantha AU - Tang, Shuli AU - Odenkirk, Melanie T. AU - Walker, Thomas AU - Stover, Lauren AU - Lyu, Jixing AU - Zhang, Tianqi AU - Russell, David AU - Baker, Erin S. AU - Yan, Xin AU - Laganowsky, Arthur T2 - JOURNAL OF THE AMERICAN CHEMICAL SOCIETY AB - TRAAK and TREK2 are two-pore domain K+ (K2P) channels and are modulated by diverse factors including temperature, membrane stretching, and lipids, such as phosphatidic acid. In addition, copper and zinc, both of which are essential for life, are known to regulate TREK2 and a number of other ion channels. However, the role of ions in the association of lipids with integral membrane proteins is poorly understood. Here, we discover cupric ions selectively modulate the binding of phosphatidylserine (PS) to TRAAK but not TREK2. Other divalent cations (Ca2+, Mg2+, and Zn2+) bind both channels but have no impact on binding PS and other lipids. Additionally, TRAAK binds more avidly to Cu2+ and Zn2+ than TREK2. In the presence of Cu2+, TRAAK binds similarly to PS with different acyl chains, indicating a crucial role of the serine headgroup in coordinating Cu2+. High-resolution native mass spectrometry (MS) enables the determination of equilibrium binding constants for distinct Cu2+-bound stoichiometries and uncovered the highest coupling factor corresponds to a 1:1 PS-to-Cu2+ ratio. Interestingly, the next three highest coupling factors had a ∼1.5:1 PS-to-Cu2+ ratio. Our findings bring forth the role of cupric ions as an essential cofactor in selective TRAAK-PS interactions. DA - 2022/4/27/ PY - 2022/4/27/ DO - 10.1021/jacs.2c00612 VL - 144 IS - 16 SP - 7048-7053 SN - 1520-5126 ER - TY - JOUR TI - Per- and polyfluoroalkyl substances (PFAS) in river discharge: Modeling loads upstream and downstream of a PFAS manufacturing plant in the Cape Fear watershed, North Carolina AU - Petre, M-A AU - Salk, K. R. AU - Stapleton, H. M. AU - Ferguson, P. L. AU - Tait, G. AU - Obenour, D. R. AU - Knappe, D. R. U. AU - Genereux, D. P. T2 - SCIENCE OF THE TOTAL ENVIRONMENT AB - The Cape Fear River is an important source of drinking water in North Carolina, and many drinking water intakes in the watershed are affected by per- and polyfluoroalkyl substances (PFAS). We quantified PFAS concentrations and loads in river water upstream and downstream of a PFAS manufacturing plant that has been producing PFAS since 1980. River samples collected from September 2018 to February 2021 were analyzed for 13 PFAS at the upstream station and 43-57 PFAS downstream near Wilmington. Frequent PFAS sampling (daily to weekly) was conducted close to gauging stations (critical to load estimation), and near major drinking water intakes (relevant to human exposure). Perfluoroalkyl acids dominated upstream while fluoroethers associated with the plant made up about 47% on average of the detected PFAS downstream. Near Wilmington, Σ43PFAS concentration averaged 143 ng/L (range 40-377) and Σ43PFAS load averaged 3440 g/day (range 459-17,300), with 17-88% originating from the PFAS plant. LOADEST was a useful tool in quantifying individual and total quantified PFAS loads downstream, however, its use was limited at the upstream station where PFAS levels in the river were affected by variable inputs from a wastewater treatment plant. Long-term monitoring of PFAS concentrations is warranted, especially at the downstream station. Results suggest a slight downward trend in PFAS levels downstream, as indicated by a decrease in flow-weighted mean concentrations and the best-fitting LOADEST model. However, despite the cessation of PFAS process wastewater discharge from the plant in November 2017, and the phase-out of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in North America, both fluoroethers and legacy PFAS continue to reach the river in significant quantities, reflecting groundwater discharge to the river and other continuing inputs. Persistence of PFAS in surface water and drinking water supplies suggests that up to 1.5 million people in the Cape Fear watershed might be exposed. DA - 2022/7/20/ PY - 2022/7/20/ DO - 10.1016/j.scitotenv.2022.154763 VL - 831 SP - SN - 1879-1026 KW - PFAS KW - Mass load KW - Model KW - Source tracking KW - Environmental monitoring KW - Drinking water ER - TY - JOUR TI - High-Resolution Demultiplexing (HRdm) Ion Mobility Spectrometry-Mass Spectrometry for Aspartic and Isoaspartic Acid Determination and Screening AU - Butler, Karen E. AU - Dodds, James N. AU - Flick, Tawnya AU - Campuzano, Iain D. G. AU - Baker, Erin S. T2 - ANALYTICAL CHEMISTRY AB - Isomeric peptide analyses are an analytical challenge of great importance to therapeutic monoclonal antibody and other biotherapeutic product development workflows. Aspartic acid (Asp, D) to isoaspartic acid (isoAsp, isoD) isomerization is a critical quality attribute (CQA) that requires careful control, monitoring, and quantitation during the drug discovery and production processes. While the formation of isoAsp has been implicated in a variety of disease states such as autoimmune diseases and several types of cancer, it is also understood that the formation of isoAsp results in a structural change impacting efficacy, potency, and immunogenic properties, all of which are undesirable. Currently, lengthy ultrahigh-performance liquid chromatography (UPLC) separations are coupled with MS for CQA analyses; however, these measurements often take over an hour and drastically limit analysis throughput. In this manuscript, drift tube ion mobility spectrometry–mass spectrometry (DTIMS–MS) and both a standard and high-resolution demultiplexing approach were utilized to study eight isomeric Asp and isoAsp peptide pairs. While the limited resolving power associated with the standard DTIMS analysis only separated three of the eight pairs, the application of HRdm distinguished seven of the eight and was only unable to separate DL and isoDL. The rapid high-throughput HRdm DTIMS–MS method was also interfaced with both flow injection and an automated solid phase extraction system to present the first application of HRdm for isoAsp and Asp assessment and demonstrate screening capabilities for isomeric peptides in complex samples, resulting in a workflow highly suitable for biopharmaceutical research needs. DA - 2022/4/26/ PY - 2022/4/26/ DO - 10.1021/acs.analchem.1c05533 VL - 94 IS - 16 SP - 6191-6199 SN - 1520-6882 ER - TY - JOUR TI - A highly diverse set of novel immunoglobulin-like transcript (NILT) genes in zebrafish indicates a wide range of functions with complex relationships to mammalian receptors AU - Wcisel, Dustin J. AU - Dornburg, Alex AU - McConnell, Sean C. AU - Hernandez, Kyle M. AU - Andrade, Jorge AU - Jong, Jill L. O. AU - Litman, Gary W. AU - Yoder, Jeffrey A. AB - Abstract Multiple novel immunoglobulin-like transcripts (NILTs) have been identified from salmon, trout and carp. NILTs typically encode activating or inhibitory transmembrane receptors with extracellular immunoglobulin (Ig) domains. Although predicted to provide immune recognition in ray-finned fish, we currently lack a definitive framework of NILT diversity, thereby limiting our predictions for their evolutionary origin and function. In order to better understand the diversity of NILTs and their possible roles in immune function, we identified five NILT loci in the Atlantic salmon ( Salmo salar) genome, defined 86 NILT Ig domains within a 3 Mbp region of zebrafish ( Danio rerio ) chromosome 1, and described 41 NILT Ig domains as part of an alternative haplotype for this same genomic region. We then identified transcripts encoded by 43 different NILT genes which reflect an unprecedented diversity of Ig domain sequences and combinations for a family of non-recombining receptors within a single species. Zebrafish NILTs include a sole putative activating receptor but extensive inhibitory and secreted forms as well as membrane-bound forms with no known signaling motifs. These results reveal a higher level of genetic complexity, interindividual variation and sequence diversity for NILTs than previously described, suggesting that this gene family likely plays multiple roles in host immunity. DA - 2022/4/22/ PY - 2022/4/22/ DO - 10.1101/2022.04.21.489081 VL - 4 UR - https://doi.org/10.1101/2022.04.21.489081 ER - TY - JOUR TI - Characterization of compositional variability in petroleum substances AU - Roman-Hubers, Alina T. AU - Cordova, Alexandra C. AU - Rohde, Arlean M. AU - Chiu, Weihsueh A. AU - McDonald, Thomas J. AU - Wright, Fred A. AU - Dodds, James N. AU - Baker, Erin S. AU - Rusyn, Ivan T2 - FUEL AB - In the process of registration of substances of Unknown or Variable Composition, Complex Reaction Products or Biological Materials (UVCBs), information sufficient to enable substance identification must be provided. Substance identification for UVCBs formed through petroleum refining is particularly challenging due to their chemical complexity, as well as variability in refining process conditions and composition of the feedstocks. This study aimed to characterize compositional variability of petroleum UVCBs both within and across product categories. We utilized ion mobility spectrometry (IMS)-MS as a technique to evaluate detailed chemical composition of independent production cycle-derived samples of 6 petroleum products from 3 manufacturing categories (heavy aromatic, hydrotreated light paraffinic, and hydrotreated heavy paraffinic). Atmospheric pressure photoionization and drift tube IMS-MS were used to identify structurally related compounds and quantified between- and within-product variability. In addition, we determined both individual molecules and hydrocarbon blocks that were most variable in samples from different production cycles. We found that detailed chemical compositional data on petroleum UVCBs obtained from IMS-MS can provide the information necessary for hazard and risk characterization in terms of quantifying the variability of the products in a manufacturing category, as well as in subsequent production cycles of the same product. DA - 2022/6/1/ PY - 2022/6/1/ DO - 10.1016/j.fuel.2022.123547 VL - 317 SP - SN - 1873-7153 KW - UVCB KW - Registration KW - Variability KW - IMS-MS ER - TY - JOUR TI - Systematic developmental toxicity assessment of a structurally diverse library of PFAS in zebrafish AU - Truong, Lisa AU - Rericha, Yvonne AU - Thunga, Preethi AU - Marvel, Skylar AU - Wallis, Dylan AU - Simonich, Michael T. AU - Field, Jennifer A. AU - Cao, Dunping AU - Reif, David M. AU - Tanguay, Robyn L. T2 - JOURNAL OF HAZARDOUS MATERIALS AB - Per- and polyfluoroalkyl substances (PFAS) are a class of widely used chemicals with limited human health effects data relative to the diversity of structures manufactured. To help fill this data gap, an extensive in vivo developmental toxicity screen was performed on 139 PFAS provided by the US EPA. Dechorionated embryonic zebrafish were exposed to 10 nominal water concentrations of PFAS (0.015–100 µM) from 6 to 120 h post-fertilization (hpf). The embryos were assayed for embryonic photomotor response (EPR), larval photomotor response (LPR), and 13 morphological endpoints. A total of 49 PFAS (35%) were bioactive in one or more assays (11 altered EPR, 25 altered LPR, and 31 altered morphology). Perfluorooctanesulfonamide (FOSA) was the only structure that was bioactive in all 3 assays, while Perfluorodecanoic acid (PFDA) was the most potent teratogen. Low PFAS volatility was associated with developmental toxicity (p < 0.01), but no association was detected between bioactivity and five other physicochemical parameters. The bioactive PFAS were enriched for 6 supergroup chemotypes. The results illustrate the power of a multi-dimensional in vivo platform to assess the developmental (neuro)toxicity of diverse PFAS and in the acceleration of PFAS safety research. DA - 2022/6/5/ PY - 2022/6/5/ DO - 10.1016/j.jhazmat.2022.128615 VL - 431 SP - SN - 1873-3336 KW - PFAS KW - Developmental toxicity KW - Structure-activity relationship KW - Abnormal behavior KW - Zebrafish ER - TY - JOUR TI - ToxPi*GIS Toolkit: creating, viewing, and sharing integrative visualizations for geospatial data using ArcGIS AU - Fleming, Jonathon AU - Marvel, Skylar W. AU - Supak, Stacy AU - Motsinger-Reif, Alison A. AU - Reif, David M. T2 - JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY AB - Presenting a comprehensive picture of geographic data comprising multiple factors is an inherently integrative undertaking. Visualizing such data in an interactive form is essential for public sharing and geographic information systems (GIS) analysis. The Toxicological Prioritization Index (ToxPi) framework offers a visual analytic integrating data that is compatible with geographic data. ArcGIS is a predominant geospatial software available for presenting and communicating geographic data, yet to our knowledge there is no methodology for integrating ToxPi profiles into ArcGIS maps.We introduce an actively developed suite of software, the ToxPi*GIS Toolkit, for creating, viewing, sharing, and analyzing interactive ToxPi profiles in ArcGIS to allow for new GIS analysis and an avenue for providing geospatial results to the public.The ToxPi*GIS Toolkit is a collection of methods for creating interactive feature layers that contain ToxPi profiles. It currently includes an ArcGIS Toolbox (ToxPiToolbox.tbx) for drawing location-specific ToxPi profiles in a single feature layer, a collection of modular Python scripts that create predesigned layer files containing ToxPi feature layers from the command line, and a collection of Python routines for useful data manipulation and preprocessing. We present workflows documenting ToxPi feature layer creation, sharing, and embedding for both novice and advanced users looking for additional customizability.Map visualizations created with the ToxPi*GIS Toolkit can be made freely available on public URLs, allowing users without ArcGIS Pro access or expertise to view and interact with them. Novice users with ArcGIS Pro access can create de novo custom maps, and advanced users can exploit additional customization options. The ArcGIS Toolbox provides a simple means for generating ToxPi feature layers. We illustrate its usage with current COVID-19 data to compare drivers of pandemic vulnerability in counties across the United States.The integration of ToxPi profiles with ArcGIS provides new avenues for geospatial analysis, visualization, and public sharing of multi-factor data. This allows for comparison of data across a region, which can support decisions that help address issues such as disease prevention, environmental health, natural disaster prevention, chemical risk, and many others. Development of new features, which will advance the interests of the scientific community in many fields, is ongoing for the ToxPi*GIS Toolkit, which can be accessed from www.toxpi.org . DA - 2022/4/26/ PY - 2022/4/26/ DO - 10.1038/s41370-022-00433-w VL - 4 SP - SN - 1559-064X KW - Visual analytics KW - Geographic information systems KW - Data integration ER - TY - JOUR TI - Transcriptome annotation reveals minimal immunogenetic diversity among Wyoming toads, Anaxyrus baxteri AU - Carlson, Kara B. AU - Wcisel, Dustin J. AU - Ackerman, Hayley D. AU - Romanet, Jessica AU - Christiansen, Emily F. AU - Niemuth, Jennifer N. AU - Williams, Christina AU - Breen, Matthew AU - Stoskopf, Michael K. AU - Dornburg, Alex AU - Yoder, Jeffrey A. T2 - CONSERVATION GENETICS AB - Briefly considered extinct in the wild, the future of the Wyoming toad (Anaxyrus baxteri) continues to rely on captive breeding to supplement the wild population. Given its small natural geographic range and history of rapid population decline at least partly due to fungal disease, investigation of the diversity of key receptor families involved in the host immune response represents an important conservation need. Population decline may have reduced immunogenetic diversity sufficiently to increase the vulnerability of the species to infectious diseases. Here we use comparative transcriptomics to examine the diversity of toll-like receptors and major histocompatibility complex (MHC) sequences across three individual Wyoming toads. We find reduced diversity at MHC genes compared to bufonid species with a similar history of bottleneck events. Our data provide a foundation for future studies that seek to evaluate the genetic diversity of Wyoming toads, identify biomarkers for infectious disease outcomes, and guide breeding strategies to increase genomic variability and wild release successes. DA - 2022/4/28/ PY - 2022/4/28/ DO - 10.1007/s10592-022-01444-8 VL - 4 SP - SN - 1572-9737 KW - Amphibian KW - Bufonidae KW - Immunogenetics KW - MHC KW - TLR KW - Transcriptomics ER - TY - JOUR TI - Comparison of National Vulnerability Indices Used by the Centers for Disease Control and Prevention for the COVID-19 Response AU - Wolkin, Amy AU - Collier, Sarah AU - House, John AU - Reif, David AU - Motsinger-Reif, Alison AU - Duca, Lindsey AU - Sharpe, Danielle T2 - PUBLIC HEALTH REPORTS AB - Objective: Vulnerability indices use quantitative indicators and geospatial data to examine the level of vulnerability to morbidity in a community. The Centers for Disease Control and Prevention (CDC) uses 3 indices for the COVID-19 response: the CDC Social Vulnerability Index (CDC-SVI), the US COVID-19 Community Vulnerability Index (CCVI), and the Pandemic Vulnerability Index (PVI). The objective of this review was to describe these tools and explain the similarities and differences between them. Methods: We described the 3 indices, outlined the underlying data sources and metrics for each, and discussed their use by CDC for the COVID-19 response. We compared the percentile score for each county for each index by calculating Spearman correlation coefficients (Spearman ρ). Results: These indices have some, but not all, component metrics in common. The CDC-SVI is a validated metric that estimates social vulnerability, which comprises the underlying population-level characteristics that influence differences in health risk among communities. To address risk specific to the COVID-19 pandemic, the CCVI and PVI build on the CDC-SVI and include additional variables. The 3 indices were highly correlated. Spearman ρ for comparisons between the CDC-SVI score and the CCVI and between the CCVI and the PVI score was 0.83. Spearman ρ for the comparison between the CDC-SVI score and PVI score was 0.73. Conclusion: The indices can empower local and state public health officials with additional information to focus resources and interventions on disproportionately affected populations to combat the ongoing pandemic and plan for future pandemics. DA - 2022/5/5/ PY - 2022/5/5/ DO - 10.1177/00333549221090262 VL - 5 SP - SN - 1468-2877 UR - https://doi.org/10.1177/00333549221090262 KW - COVID-19 KW - vulnerability KW - social vulnerability index KW - GIS KW - geographic information systems ER - TY - JOUR TI - A Preprocessing Tool for Enhanced Ion Mobility-Mass Spectrometry-Based Omics Workflows AU - Bilbao, Aivett AU - Gibbons, Bryson C. AU - Stow, Sarah M. AU - Kyle, Jennifer E. AU - Bloodsworth, Kent J. AU - Payne, Samuel H. AU - Smith, Richard D. AU - Ibrahim, Yehia M. AU - Baker, Erin S. AU - Fjeldsted, John C. T2 - JOURNAL OF PROTEOME RESEARCH AB - The ability to improve the data quality of ion mobility-mass spectrometry (IM-MS) measurements is of great importance for enabling modular and efficient computational workflows and gaining better qualitative and quantitative insights from complex biological and environmental samples. We developed the PNNL PreProcessor, a standalone and user-friendly software housing various algorithmic implementations to generate new MS-files with enhanced signal quality and in the same instrument format. Different experimental approaches are supported for IM-MS based on Drift-Tube (DT) and Structures for Lossless Ion Manipulations (SLIM), including liquid chromatography (LC) and infusion analyses. The algorithms extend the dynamic range of the detection system, while reducing file sizes for faster and memory-efficient downstream processing. Specifically, multidimensional smoothing improves peak shapes of poorly defined low-abundance signals, and saturation repair reconstructs the intensity profile of high-abundance peaks from various analyte types. Other functionalities are data compression and interpolation, IM demultiplexing, noise filtering by low intensity threshold and spike removal, and exporting of acquisition metadata. Several advantages of the tool are illustrated, including an increase of 19.4% in lipid annotations and a two-times faster processing of LC-DT IM-MS data-independent acquisition spectra from a complex lipid extract of a standard human plasma sample. The software is freely available at https://omics.pnl.gov/software/pnnl-preprocessor. DA - 2022/3/4/ PY - 2022/3/4/ DO - 10.1021/acs.jproteome.1c00425 VL - 21 IS - 3 SP - 798-807 SN - 1535-3907 KW - mass spectrometry KW - ion mobility spectrometry KW - preprocessing software KW - time-of-flight detector saturation KW - data-independent acquisition KW - lipid annotation ER - TY - JOUR TI - Multimodal Mass Spectrometry Imaging of Rat Brain Using IR-MALDESI and NanoPOTS-LC-MS/MS AU - Pace, Crystal L. AU - Simmons, Jared AU - Kelly, Ryan T. AU - Muddiman, David C. T2 - JOURNAL OF PROTEOME RESEARCH AB - Multimodal mass spectrometry imaging (MSI) is a critical technique used for deeply investigating biological systems by combining multiple MSI platforms in order to gain the maximum molecular information about a sample that would otherwise be limited by a single analytical technique. The aim of this work was to create a multimodal MSI approach that measures metabolomic and proteomic data from a single biological organ by combining infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) for metabolomic MSI and nanodroplet processing in one pot for trace samples (nanoPOTS) LC-MS/MS for spatially resolved proteome profiling. Adjacent tissue sections of rat brain were analyzed by each platform, and each data set was individually analyzed using previously optimized workflows. IR-MALDESI data sets were annotated by accurate mass and spectral accuracy using HMDB, METLIN, and LipidMaps databases, while nanoPOTS-LC-MS/MS data sets were searched against the rat proteome using the Sequest HT algorithm and filtered with a 1% FDR. The combined data revealed complementary molecular profiles distinguishing the corpus callosum against other sampled regions of the brain. A multiomic pathway integration showed a strong correlation between the two data sets when comparing average abundances of metabolites and corresponding enzymes in each brain region. This work demonstrates the first steps in the creation of a multimodal MSI technique that combines two highly sensitive and complementary imaging platforms. Raw data files are available in METASPACE (https://metaspace2020.eu/project/pace-2021) and MassIVE (identifier: MSV000088211). DA - 2022/3/4/ PY - 2022/3/4/ DO - 10.1021/acs.jproteome.1c00641 VL - 21 IS - 3 SP - 713-720 SN - 1535-3907 KW - multimodal mass spectrometry imaging KW - multiomic analyses KW - IR-MALDESI KW - nanoPOTS-LC-MS/MS ER - TY - JOUR TI - Multiple Infusion Start Time Mass Spectrometry Imaging of Dynamic SIL-Glutathione Biosynthesis Using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization AU - Mellinger, Allyson L. AU - Garrard, Kenneth P. AU - Khodjaniyazova, Sitora AU - Rabbani, Zahid N. AU - Gamcsik, Michael P. AU - Muddiman, David C. T2 - JOURNAL OF PROTEOME RESEARCH AB - Due to the high association of glutathione metabolism perturbation with a variety of disease states, there is a dire need for analytical techniques to study glutathione kinetics. Additionally, the elucidation of microenvironmental effects on changes in glutathione metabolism would significantly improve our understanding of the role of glutathione in disease. We therefore present a study combining a multiple infusion start time protocol, stable isotope labeling technology, infrared matrix-assisted laser desorption electrospray ionization, and high-resolution accurate mass-mass spectrometry imaging to study spatial changes in glutathione kinetics across in sectioned mouse liver tissues. After injecting a mouse with the isotopologues [2-13C,15N]-glycine, [1,2-13C2]-glycine, and [1,2-13C2,15N]-glycine at three different time points, we were able to fully resolve and spatially map their metabolism into three isotopologues of glutathione and calculate their isotopic enrichment in glutathione. We created a tool in the open-source mass spectrometry imaging software MSiReader to accurately compute the percent isotope enrichment (PIE) of these labels in glutathione and visualize them in heat-maps of the tissue sections. In areas of high flux, we found that each label enriched an approximate median of 1.6%, 1.8%, and 1.5%, respectively, of the glutathione product pool measured in each voxel. This method may be adapted to study the heterogeneity of glutathione flux in diseased versus healthy tissues. DA - 2022/3/4/ PY - 2022/3/4/ DO - 10.1021/acs.jproteome.1c00636 VL - 21 IS - 3 SP - 747-757 SN - 1535-3907 KW - IR-MALDESI KW - mass spectrometry imaging KW - stable isotope labeling KW - glutathione KW - kinetic metabolism ER - TY - JOUR TI - The Ahr2-Dependent wfikkn1 Gene Influences Zebrafish Transcriptome, Proteome, and Behavior AU - Shankar, Prarthana AU - Garcia, Gloria R. AU - LaDu, Jane K. AU - Sullivan, Christopher M. AU - Dunham, Cheryl L. AU - Goodale, Britton C. AU - Waters, Katrina M. AU - Stanisheuski, Stanislau AU - Maier, Claudia S. AU - Thunga, Preethi AU - Reif, David M. AU - Tanguay, Robyn L. T2 - TOXICOLOGICAL SCIENCES AB - The aryl hydrocarbon receptor (AHR) is required for vertebrate development and is also activated by exogenous chemicals, including polycyclic aromatic hydrocarbons (PAHs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AHR activation is well-understood, but roles of downstream molecular signaling events are largely unknown. From previous transcriptomics in 48 h postfertilization (hpf) zebrafish exposed to several PAHs and TCDD, we found wfikkn1 was highly coexpressed with cyp1a (marker for AHR activation). Thus, we hypothesized wfikkn1's role in AHR signaling, and showed that wfikkn1 expression was Ahr2 (zebrafish ortholog of human AHR)-dependent in developing zebrafish exposed to TCDD. To functionally characterize wfikkn1, we made a CRISPR-Cas9 mutant line with a 16-bp deletion in wfikkn1's exon, and exposed wildtype and mutants to dimethyl sulfoxide or TCDD. 48-hpf mRNA sequencing revealed over 700 genes that were differentially expressed (p < .05, log2FC > 1) between each pair of treatment combinations, suggesting an important role for wfikkn1 in altering both the 48-hpf transcriptome and TCDD-induced expression changes. Mass spectrometry-based proteomics of 48-hpf wildtype and mutants revealed 325 significant differentially expressed proteins. Functional enrichment demonstrated wfikkn1 was involved in skeletal muscle development and played a role in neurological pathways after TCDD exposure. Mutant zebrafish appeared morphologically normal but had significant behavior deficiencies at all life stages, and absence of Wfikkn1 did not significantly alter TCDD-induced behavior effects at all life stages. In conclusion, wfikkn1 did not appear to be significantly involved in TCDD's overt toxicity but is likely a necessary functional member of the AHR signaling cascade. DA - 2022/4/4/ PY - 2022/4/4/ DO - 10.1093/toxsci/kfac037 VL - 4 SP - SN - 1096-0929 KW - aryl hydrocarbon receptor (AHR) KW - zebrafish KW - TCDD KW - wfikkn1 KW - transcriptomics KW - behavior ER - TY - JOUR TI - Exposure to common-use pesticides, manganese, lead, and thyroid function among pregnant women from the Infants' Environmental Health (ISA) study, Costa Rica AU - Vargas, Andrea Corrales AU - Castaneda, Jorge Penaloza AU - Liljedahl, Emelie Rietz AU - Mora, Ana Maria AU - Menezes-Filho, Jose Antonio AU - Smith, Donald R. AU - Mergler, Donna AU - Reich, Brian AU - Giffin, Andrew AU - Hoppin, Jane A. AU - Lindh, Christian H. AU - Joode, Berna van Wendel T2 - SCIENCE OF THE TOTAL ENVIRONMENT AB - Pesticides and metals may disrupt thyroid function, which is key to fetal brain development.To evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA).At enrollment, we determined women's (n = 400) specific-gravity corrected urinary pesticide (μg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (μg/g) and blood (MnB) (μg/L), and blood lead (PbB) (μg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n = 400), and about ten weeks afterwards (n = 245). We assessed associations between exposures and outcomes with linear regression and general additive models, Bayesian multivariate linear regression, and Bayesian kernel machine regression.About 80%, 94%, and 100% of the women had TSH, FT4, and FT3 within clinical reference ranges, respectively. Women with higher urinary ETU, and pyrimethanil-metabolites, had lower FT4: β = -0.79 (95%CI = -1.51, -0.08) and β = -0.29 (95%CI = -0.62, -0.03), respectively, for each tenfold increase in exposure. MnB was positively associated with FT4 (β = 0.04 (95%CI = 0.00, 0.07 per 1 μg/L increase), and women with high urinary pyrethroid-metabolite concentrations had decreased TSH (non-linear effects). For the late-effect analysis, metabolites of pyrethroids and chlorpyrifos, as well as MnH, and PbB were associated decreased TSH, or increased FT4 and/or FT3.Mancozeb (ETU) and pyrimethanil may inhibit FT4 secretion (hypothyroidism-like effect), while chlorpyrifos, pyrethroids, MnB, MnH, PbB and Mn showed hyperthyroidism-like effects. Some effects on thyroid homeostasis seemed to be immediate (mancozeb (ETU), pyrimethanil, MnB), others delayed (chlorpyrifos, MnH, PbB), or both (pyrethroids), possibly reflecting different mechanisms of action. DA - 2022/3/1/ PY - 2022/3/1/ DO - 10.1016/j.scitotenv.2021.151288 VL - 810 SP - SN - 1879-1026 KW - Thyroid function KW - Endocrine disruptors KW - Pesticides KW - Metals KW - Latin America ER - TY - JOUR TI - Mechanisms of orthophosphate removal from water by lanthanum carbonate and other lanthanum-containing materials AU - Zhi, Yue AU - Paterson, Alisa R. AU - Call, Douglas F. AU - Jones, Jacob L. AU - Hesterberg, Dean AU - Duckworth, Owen W. AU - Poitras, Eric P. AU - Knappe, Detlef R. U. T2 - SCIENCE OF THE TOTAL ENVIRONMENT AB - Removing phosphorus (P) from water and wastewater is essential for preventing eutrophication and protecting environmental quality. Lanthanum [La(III)]-containing materials can effectively and selectively remove orthophosphate (PO4) from aqueous systems, but there remains a need to better understand the underlying mechanism of PO4 removal. Our objectives were to 1) identify the mechanism of PO4 removal by La-containing materials and 2) evaluate the ability of a new material, La2(CO3)3(s), to remove PO4 from different aqueous matrices, including municipal wastewater. We determined the dominant mechanism of PO4 removal by comparing geochemical simulations with equilibrium data from batch experiments and analyzing reaction products by X-ray diffraction and scanning transmission electron microscopy with energy dispersive spectroscopy. Geochemical simulations of aqueous systems containing PO4 and La-containing materials predicted that PO4 removal occurs via precipitation of poorly soluble LaPO4(s). Results from batch experiments agreed with those obtained from geochemical simulations, and mineralogical characterization of the reaction products were consistent with PO4 removal occurring primarily by precipitation of LaPO4(s). Between pH 1.5 and 12.9, La2(CO3)3(s) selectively removed PO4 over other anions from different aqueous matrices, including treated wastewater. However, the rate of PO4 removal decreased with increasing solution pH. In comparison to other solids, such as La(OH)3(s), La2(CO3)3(s) exhibits a relatively low solubility, particularly under slightly acidic conditions. Consequently, release of La3+ into the environment can be minimized when La2(CO3)3(s) is deployed for PO4 sequestration. DA - 2022/5/10/ PY - 2022/5/10/ DO - 10.1016/j.scitotenv.2022.153153 VL - 820 SP - SN - 1879-1026 KW - Lanthanum containing material KW - Lanthanum carbonate KW - Phosphorus removal KW - Wastewater treatment KW - Mineral precipitation ER - TY - JOUR TI - Per- and polyfluoroalkyl substances in the environment AU - Evich, Marina G. AU - Davis, Mary J. B. AU - McCord, James P. AU - Acrey, Brad AU - Awkerman, Jill A. AU - Knappe, Detlef R. U. AU - Lindstrom, Andrew B. AU - Speth, Thomas F. AU - Tebes-Stevens, Caroline AU - Strynar, Mark J. AU - Wang, Zhanyun AU - Weber, Eric J. AU - Henderson, W. Matthew AU - Washington, John W. T2 - SCIENCE AB - Over the past several years, the term PFAS (per- and polyfluoroalkyl substances) has grown to be emblematic of environmental contamination, garnering public, scientific, and regulatory concern. PFAS are synthesized by two processes, direct fluorination (e.g., electrochemical fluorination) and oligomerization (e.g., fluorotelomerization). More than a megatonne of PFAS is produced yearly, and thousands of PFAS wind up in end-use products. Atmospheric and aqueous fugitive releases during manufacturing, use, and disposal have resulted in the global distribution of these compounds. Volatile PFAS facilitate long-range transport, commonly followed by complex transformation schemes to recalcitrant terminal PFAS, which do not degrade under environmental conditions and thus migrate through the environment and accumulate in biota through multiple pathways. Efforts to remediate PFAS-contaminated matrices still are in their infancy, with much current research targeting drinking water. DA - 2022/2/4/ PY - 2022/2/4/ DO - 10.1126/science.abg9065 VL - 375 IS - 6580 SP - 512-+ SN - 1095-9203 UR - https://doi.org/10.1126/science.abg9065 ER - TY - JOUR TI - Development and validation of a high resolving power absolute quantitative per- and polyfluoroalkyl substances method incorporating Skyline data processing AU - Enders, Jeffrey R. AU - Weed, Rebecca A. AU - Griffith, Emily H. AU - Muddiman, David C. T2 - RAPID COMMUNICATIONS IN MASS SPECTROMETRY AB - The ability to perform absolute quantitation and non-targeted analysis on a single mass spectrometry instrument would be advantageous to many researchers studying per- and polyfluoroalkyl substances (PFAS). High-resolution accurate mass (HRAM) instrumentation (typically deployed for non-targeted work) carries several advantages over traditional triple quadrupole workflows when performing absolute quantitation. Processing this data using a vendor-neutral software would promote collaboration for these environmental studies.LC-MS (Orbitrap Exploris 240) was used for absolute quantitation of 45 PFAS using precursor (MS1) peak areas for quantitation, whereas isotope pattern matching and fragmentation (MS2) pattern matching were used for qualitative identification. In addition, a fluorinated chromatographic column achieved superior separation compared to the typical C18 columns typically used in PFAS analyses. This method was validated across eight different chemical classes using recommended guidelines found in EPA Method 537.1 and Skyline data processing software.The validated limits of all 45 compounds, as well as metrics or accuracy and reproducibility, are reported. Most compounds achieved limits of quantitation in the range of 2-50 ng/L. Four newly released Chemours-specific compounds (PEPA, PFO3OA, PFO4DA, and PFO5DoA) were also validated. Aspects of data analysis specific to high resolving power absolute quantitation are reviewed as are the details of processing these data via Skyline.This method shows the feasibility of performing reproducible absolute quantitation of PFAS on an HRAM platform and does so using an open-source vendor-neutral data processing software to facilitate sharing of data across labs and institutions. DA - 2022/6/15/ PY - 2022/6/15/ DO - 10.1002/rcm.9295 VL - 36 IS - 11 SP - SN - 1097-0231 ER - TY - JOUR TI - Per- and Polyfluoroalkyl Substances (PFAS) in Facemasks: Potential Source of Human Exposure to PFAS with Implications for Disposal to Landfills AU - Muensterman, Derek J. AU - Cahuas, Liliana AU - Titaley, Ivan A. AU - Schmokel, Christopher AU - Cruz, Florentino B. AU - Barlaz, Morton A. AU - Carignan, Courtney C. AU - Peaslee, Graham F. AU - Field, Jennifer A. T2 - ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS AB - Facemasks are important tools for fighting against disease spread, including Covid-19 and its variants, and some may be treated with per- and polyfluoroalkyl substances (PFAS). Nine facemasks over a range of prices were analyzed for total fluorine and PFAS. The PFAS compositions of the masks were then used to estimate exposure and the mass of PFAS discharged to landfill leachate. Fluorine from PFAS accounted only for a small fraction of total fluorine. Homologous series of linear perfluoroalkyl carboxylates and the 6:2 fluorotelomer alcohol indicated a fluorotelomer origin. Inhalation was estimated to be the dominant exposure route (40%-50%), followed by incidental ingestion (15%-40%) and dermal (11%-20%). Exposure and risk estimates were higher for children than adults, and high physical activity substantially increased inhalation exposure. These preliminary findings indicate that wearing masks treated with high levels of PFAS for extended periods of time can be a notable source of exposure and have the potential to pose a health risk. Despite modeled annual disposal of ~29-91 billion masks, and an assuming 100% leaching of individual PFAS into landfill leachate, mask disposal would contribute only an additional 6% of annual PFAS mass loads and less than 11 kg of PFAS discharged to U.S. wastewater. DA - 2022/4/12/ PY - 2022/4/12/ DO - 10.1021/acs.estlett.2c00019 VL - 9 IS - 4 SP - 320-326 SN - 2328-8930 UR - https://doi.org/10.1021/acs.estlett.2c00019 KW - PFAS KW - facemasks KW - Covid-19 KW - total fluorine KW - LC-qTOF KW - GC-MS KW - exposure KW - landfill ER - TY - JOUR TI - Respiratory and allergic outcomes among 5-year-old children exposed to pesticides AU - Islam, Jessica Y. AU - Hoppin, Jane AU - Mora, Ana M. AU - Soto-Martinez, Manuel E. AU - Cordoba Gamboa, Leonel AU - Penaloza Castaneda, Jorge Ernesto AU - Reich, Brian AU - Lindh, Christian AU - Joode, Berna T2 - THORAX AB - Background Little is known about the effects of pesticides on children’s respiratory and allergic outcomes. We evaluated associations of prenatal and current pesticide exposures with respiratory and allergic outcomes in children from the Infants’ Environmental Health Study in Costa Rica. Methods Among 5-year-old children (n=303), we measured prenatal and current specific gravity-corrected urinary metabolite concentrations of insecticides (chlorpyrifos, pyrethroids), fungicides (mancozeb, pyrimethanil, thiabendazole) and 2,4-D. We collected information from caregivers on respiratory (ever doctor-diagnosed asthma and lower respiratory tract infections (LRTI), wheeze and cough during last 12 months) and allergic (nasal allergies, itchy rash, ever eczema) outcomes. We fitted separate multivariable logistic regression models for high (≥75th percentile (P75)) vs low (<P75) metabolite concentrations with respiratory and allergic outcomes. We also ran models including metabolite concentrations as continuous exposure variables. Results Children’s respiratory outcomes were common (39% cough, 20% wheeze, 12% asthma, 5% LRTI). High current pyrethroid metabolite concentrations (∑pyrethroids) were associated with wheeze (OR=2.37, 95% CI 1.28 to 4.34), itchy rash (OR=2.74, 95% CI 1.33 to 5.60), doctor-diagnosed asthma and LRTI. High current ethylene thiourea (ETU) (specific metabolite of mancozeb) was somewhat associated with LRTI (OR=2.09, 95% CI 0.68 to 6.02). We obtained similar results when modelling ∑pyrethroids and ETU as continuous variables. We saw inconsistent or null associations for other pesticide exposures and health outcomes. Conclusions Current pyrethroid exposure may affect children’s respiratory and allergic health at 5 years of age. Current mancozeb exposure might contribute to LRTI. These findings are important as pyrethroids are broadly used in home environments and agriculture and mancozeb in agriculture. DA - 2022/2/24/ PY - 2022/2/24/ DO - 10.1136/thoraxjnl-2021-218068 VL - 2 SP - SN - 1468-3296 KW - asthma epidemiology KW - paediatric asthma KW - respiratory infection ER - TY - JOUR TI - Environmental Health Literacy as Knowing, Feeling, and Believing: Analyzing Linkages between Race, Ethnicity, and Socioeconomic Status and Willingness to Engage in Protective Behaviors against Health Threats AU - Binder, Andrew R. AU - May, Katlyn AU - Murphy, John AU - Gross, Anna AU - Carlsten, Elise T2 - INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH AB - This study investigates the relationships between environmental health literacy, the characteristics of people (race, ethnicity, and socioeconomic status) associated with health disparities, and people’s willingness to engage in protective behaviors against environmental health threats. Environmental health literacy is a framework for capturing the continuum between the knowledge of environmental impacts on public health, and the skills and decisions needed to take health-protective actions. We pay particular attention to three dimensions of environmental health literacy: factual knowledge (knowing the facts), knowledge sufficiency (feeling ready to decide what to do), and response efficacy (believing that protective behaviors work). In June 2020, we collected survey data from North Carolina residents on two topics: the viral infection COVID-19 and industrial contaminants called per- and polyfluoroalkyl substances (PFAS). We used their responses to test stepwise regression models with willingness to engage in protective behaviors as a dependent variable and other characteristics as independent variables, including environmental health literacy. For both topics, our results indicated that no disparities emerged according to socioeconomic factors (level of education, household income, or renting one’s residence). We observed disparities in willingness according to race, comparing Black to White participants, but not when comparing White to American Indian, Alaska Native, Asian, Native Hawaiian, or Pacific Islander participants nor Hispanic to non-Hispanic participants. The disparities in willingness between Black and White participants persisted until we introduced the variables of environmental health literacy, when the difference between these groups was no longer significant in the final regression models. The findings suggest that focusing on environmental health literacy could bridge a gap in willingness to protect oneself based on factors such as race/ethnicity and socioeconomic status, which have been identified in the environmental health literature as resulting in health disparities. DA - 2022/3// PY - 2022/3// DO - 10.3390/ijerph19052701 VL - 19 IS - 5 SP - SN - 1660-4601 KW - environmental health literacy KW - health disparities KW - COVID-19 KW - PFAS KW - race and ethnicity KW - socioeconomic status KW - efficacy KW - knowledge sufficiency KW - factual knowledge ER - TY - JOUR TI - Nonylphenol Polyethoxylates Enhance Adipose Deposition in Developmentally Exposed Zebrafish AU - Kassotis, Christopher D. AU - LeFauve, Matthew K. AU - Chiang, Yu-Ting Tiffany AU - Knuth, Megan M. AU - Schkoda, Stacy AU - Kullman, Seth W. T2 - Toxics AB - 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 environmental matrices. Despite a growing push for replacement products, APEOs continue to be released into the environment through wastewater at significant levels. Research into related nonionic surfactants from varying sources has reported metabolic health impacts, and we have previously demonstrated that diverse APEOs and alcohol polyethoxylates promote adipogenesis in the murine 3T3-L1 pre-adipocyte model. These effects appeared to be independent of the base alkylphenol and related to the ethoxylate chain length, though limited research has evaluated NPEO exposures in animal models. The goals of this study were to assess the potential of NPEOs to promote adiposity (Nile red fluorescence quantification) and alter growth and/or development (toxicity, length, weight, and energy expenditure) of developmentally exposed zebrafish (Danio rerio). We also sought to expand our understanding of the ability to promote adiposity through evaluation in human mesenchymal stem cells. Herein, we demonstrated consistent adipogenic effects in two separate human bone-marrow-derived mesenchymal stem cell models, and that nonylphenol and its ethoxylates promoted weight gain and increased adipose deposition in developmentally exposed zebrafish. Notably, across both cell and zebrafish models we report increasing adipogenic/obesogenic activity with increasing ethoxylate chain lengths up to maximums around NPEO-6 and then decreasing activity with the longest ethoxylate chain lengths. This research suggests metabolic health concerns for these common obesogens, suggesting further need to assess molecular mechanisms and better characterize environmental concentrations for human health risk assessments. DA - 2022/2// PY - 2022/2// DO - 10.3390/toxics10020099 VL - 10 IS - 2 SP - 99 KW - endocrine disrupting chemicals KW - adipogenesis KW - alkylphenol ethoxylates KW - ethoxylated surfactants KW - mixtures KW - obesogen ER - TY - JOUR TI - Combining Isotopologue Workflows and Simultaneous Multidimensional Separations to Detect, Identify, and Validate Metabolites in Untargeted Analyses AU - Dodds, James N. AU - Wang, Lingjue AU - Patti, Gary J. AU - Baker, Erin S. T2 - ANALYTICAL CHEMISTRY AB - While the combination of liquid chromatography and tandem mass spectrometry (LC-MS/MS) is commonly used for feature annotation in untargeted omics experiments, ensuring these prioritized features originate from endogenous metabolism remains challenging. Isotopologue workflows, such as isotopic ratio outlier analysis (IROA), mass isotopomer ratio analysis of U-13C labeled extracts (MIRACLE), and credentialing incorporate isotopic labels directly into metabolic precursors, guaranteeing that all features of interest are unequivocal byproducts of cellular metabolism. Furthermore, comprehensive separation and annotation of small molecules continue to challenge the metabolomics field, particularly for isomeric systems. In this paper, we evaluate the analytical utility of incorporating ion mobility spectrometry (IMS) as an additional separation mechanism into standard LC-MS/MS isotopologue workflows. Since isotopically labeled molecules codrift in the IMS dimension with their 12C versions, LC-IMS-CID-MS provides four dimensions (LC, IMS, MS, and MS/MS) to directly investigate the metabolic activity of prioritized untargeted features. Here, we demonstrate this additional selectivity by showcasing how a preliminary data set of 30 endogeneous metabolites are putatively annotated from isotopically labeled Escherichia coli cultures when analyzed by LC-IMS-CID-MS. Metabolite annotations were based on several molecular descriptors, including accurate mass measurement, carbon number, annotated fragmentation spectra, and collision cross section (CCS), collectively illustrating the importance of incorporating IMS into isotopologue workflows. Overall, our results highlight the enhanced separation space and increased annotation confidence afforded by IMS for metabolic characterization and provide a unique perspective for future developments in isotopically labeled MS experiments. DA - 2022/1/28/ PY - 2022/1/28/ DO - 10.1021/acs.analchem.1c04430 VL - 1 SP - SN - 1520-6882 ER - TY - JOUR TI - Empowering women and addressing underrepresentation in the field of mass spectrometry AU - Rampler, Evelyn AU - Baker, Erin S. AU - Kirkwood, Kaylie I AU - Schwaiger-Haber, Michaela AU - Tam, Maggie AU - Jones, Marissa A. AU - Sherman, Melissa T2 - EXPERT REVIEW OF PROTEOMICS DA - 2022/2/16/ PY - 2022/2/16/ DO - 10.1080/14789450.2022.2039631 VL - 2 SP - SN - 1744-8387 KW - FeMS KW - ASMS KW - mass spectrometry KW - women KW - diversity ER - TY - JOUR TI - Demonstrating a systems approach for integrating disparate data streams to inform decisions on children's environmental health AU - Hubal, Elaine A. Cohen AU - DeLuca, Nicole M. AU - Mullikin, Ashley AU - Slover, Rachel AU - Little, John C. AU - Reif, David M. T2 - BMC PUBLIC HEALTH AB - The use of systems science methodologies to understand complex environmental and human health relationships is increasing. Requirements for advanced datasets, models, and expertise limit current application of these approaches by many environmental and public health practitioners.A conceptual system-of-systems model was applied for children in North Carolina counties that includes example indicators of children's physical environment (home age, Brownfield sites, Superfund sites), social environment (caregiver's income, education, insurance), and health (low birthweight, asthma, blood lead levels). The web-based Toxicological Prioritization Index (ToxPi) tool was used to normalize the data, rank the resulting vulnerability index, and visualize impacts from each indicator in a county. Hierarchical clustering was used to sort the 100 North Carolina counties into groups based on similar ToxPi model results. The ToxPi charts for each county were also superimposed over a map of percentage county population under age 5 to visualize spatial distribution of vulnerability clusters across the state.Data driven clustering for this systems model suggests 5 groups of counties. One group includes 6 counties with the highest vulnerability scores showing strong influences from all three categories of indicators (social environment, physical environment, and health). A second group contains 15 counties with high vulnerability scores driven by strong influences from home age in the physical environment and poverty in the social environment. A third group is driven by data on Superfund sites in the physical environment.This analysis demonstrated how systems science principles can be used to synthesize holistic insights for decision making using publicly available data and computational tools, focusing on a children's environmental health example. Where more traditional reductionist approaches can elucidate individual relationships between environmental variables and health, the study of collective, system-wide interactions can enable insights into the factors that contribute to regional vulnerabilities and interventions that better address complex real-world conditions. DA - 2022/2/15/ PY - 2022/2/15/ DO - 10.1186/s12889-022-12682-3 VL - 22 IS - 1 SP - SN - 1471-2458 KW - Chemical exposure KW - ANOVA KW - ToxPi KW - Children's health KW - Environmental health KW - Systems approach KW - Multivariate analysis KW - Data-driven ER - TY - JOUR TI - Optimized C-Trap Timing of an Orbitrap 240 Mass Spectrometer for High-Throughput Screening and Native MS by IR-MALDESI AU - Knizner, Kevan T. AU - Bagley, Michael C. AU - Garrard, Kenneth P. AU - Hauschild, Jan-Peter AU - Pu, Fan AU - Elsen, Nathaniel L. AU - Williams, Jon D. AU - Muddiman, David C. T2 - JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY AB - Infrared matrix-assisted laser desorption ionization (IR-MALDESI) is a hybrid mass spectrometry ionization source that combines the benefits of electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) making it a great analytical tool for high-throughput screening (HTS) analyses. IR-MALDESI is coupled to an Orbitrap Exploris 240 mass spectrometer that utilizes a bent quadrupole (C-trap) to inject accumulated ions into the high-field Orbitrap mass analyzer. Here, we present a study on the optimized C-trap timing for HTS analyses by IR-MALDESI mass spectrometry. The timing between initial ion generation and the C-trap opening time was optimized to reduce unnecessary ambient ion accumulation in the mass spectrometer. The time in which the C-trap was held open, the ion accumulation time, was further optimized to maximize the accumulation of analyte ions generated using IR-MALDESI. The resulting C-trap opening scheme benefits small-molecule HTS analyses by IR-MALDESI by maximizing target ion abundances, minimizing ambient ion abundances, and minimizing the total analysis time per sample. The proposed C-trap timing scheme for HTS does not translate to large molecules; a NIST monoclonal antibody standard reference material was analyzed to demonstrate that larger analytes require longer ion accumulation times and that IR-MALDESI can measure intact antibodies in their native state. DA - 2022/2/2/ PY - 2022/2/2/ DO - 10.1021/jasms.1c00319 VL - 33 IS - 2 SP - 328-334 SN - 1879-1123 KW - high-throughput screening KW - IR-MALDESI KW - Orbitrap mass spectrometer KW - C-trap ER - TY - JOUR TI - Weak differences in sensitivity to major ions by different larval stages of the mayfly Neocloeon triangulifer AU - Orr, Sarah E. AU - Cochran, Jamie K. AU - Wallace, Ian G. AU - Gray, Rachel W. AU - Overmyer, Gretta E. AU - Buchwalter, David B. T2 - FRESHWATER SCIENCE AB - Freshwater salinization is a global ecological concern because of the alarming biodiversity declines associated with increases in major ion concentrations. Loss of mayfly diversity appears to be a common ecological response to anthropogenic salinization worldwide. Remarkably few regulatory standards exist to protect aquatic life from major ions, and antiquated approaches for setting such standards rely on traditional laboratory toxicity tests, which do not address sensitivities of mayflies at different larval stages. The lab-reared mayfly Neocloeon triangulifer (McDunnough, 1931) has emerged as one of the very few useful aquatic insect models for studying the effects of environmental stressors, including salinity, in the laboratory. Here, we asked if different larval life stages are differentially sensitivity to ion concentrations by conducting traditional 96-h toxicity tests with NaCl, CaCl2, and Ca/MgSO4. We used a general linear model to determine if survivorship differed among larval stages as well as ion type and concentration. We also calculated median lethal concentrations (LC50) for each larval stage. Larval sensitivity to NaCl decreased slightly with age (2–6, 9–13, and 17–21 d, with LC50 values of 401, 441, and 570 mg/L, respectively, when expressed as Na concentrations). Similarly, larval sensitivity to Ca/MgSO4 differed slightly among age groups (LC50 = 748, 1503, and 1439 mg/L, respectively, when expressed as SO4 concentrations). Reliable confidence intervals on LC50 values for CaCl2 could not be calculated because of high survivorship. However, our general linear model revealed that age played a moderate role in survival (p = 0.0065) across all salts of interest. To assess the potential changes in ion flux between larval stages, we used radiotracers (22Na, 35SO4, or 45Ca) in 18- and 25-d-old larvae and found no strong differences in ion uptake rates. We also qualitatively examined morphological differences between larval life stages, including the appearance of gills and number of ionocytes. Our results indicate that younger N. triangulifer larvae may be more sensitive to major ions than mature larvae. These results should be considered when experimentally using larger, late-stage N. triangulifer larvae to study the physiological effects and acute toxicity of salinity. DA - 2022/6/1/ PY - 2022/6/1/ DO - 10.1086/719359 SP - SN - 2161-9565 KW - salinity KW - aquatic insects KW - mayflies KW - ontogenetic KW - major ions KW - toxicity KW - freshwater salinization KW - life stage sensitivity KW - model organism ER - TY - JOUR TI - Assessing the P-crit in relation to temperature and the expression of hypoxia associated genes in the mayfly, Neocloeon triangulifer AU - Cochran, Jamie K. AU - Orr, Sarah E. AU - Buchwalter, David B. T2 - SCIENCE OF THE TOTAL ENVIRONMENT AB - Hypoxia is a growing concern in aquatic ecosystems. Historically, scientists have used the Pcrit (the dissolved oxygen level below which an animal can no longer oxyregulate) to infer hypoxia tolerance across species. Here, we tested the hypothesis that the Pcrit is positively correlated with temperature in the mayfly, Neocloeon triangulifer. Cross-temperature comparisons showed a modest (r = 0.47), but significant (p < 0.0001) association between temperature and Pcrit despite relatively large interindividual variability (Coefficient of Variance (CV) = 39.9% at 18 °C). We used the expression of hypoxia-responsive genes EGL-9 (an oxygen sensing gene and modulator of HIF-1a activity) and LDH (a hypoxia indicator) to test whether oxygen partial pressure near the Pcrit stimulates expression of hypoxia-responsive genes. Neither gene was upregulated at oxygen levels above the estimated Pcrit, however, at or below the Pcrit estimates, expression of both genes was stimulated (~20- and ~3-fold change for EGL-9 and LDH, respectively). Finally, we evaluated the influence of hypoxic exposure time and pretreatment conditions on the mRNA expression levels of hypoxia-responsive genes. When larvae were exposed to a gradual reduction of DO, hypoxic gene expression was more robust than during instantaneous exposure to hypoxia. Our data provide modest support for traditional interpretation of the Pcrit as a physiologically meaningful shift from aerobic to anaerobic metabolism in N. triangulifer. However, we also discuss limitations of the Pcrit as a proxy measure of hypoxia tolerance at the species level. DA - 2022/2/20/ PY - 2022/2/20/ DO - 10.1016/j.scitotenv.2021.151743 VL - 808 SP - SN - 1879-1026 KW - Hypoxia KW - Pcrit KW - Gene expression KW - Temperature KW - Mayfly ER - TY - JOUR TI - Gestational Cd Exposure in the CD-1 Mouse Sex-Specifically Disrupts Essential Metal Ion Homeostasis AU - Jackson, Thomas W. AU - Baars, Oliver AU - Belcher, Scott M. T2 - TOXICOLOGICAL SCIENCES AB - Abstract In CD-1 mice, gestational-only exposure to cadmium (Cd) causes female-specific hepatic insulin resistance, metabolic disruption, and obesity. To evaluate whether sex differences in uptake and changes in essential metal concentrations contribute to metabolic outcomes, placental and liver Cd and essential metal concentrations were quantified in male and female offspring perinatally exposed to 500 ppb CdCl2. Exposure resulted in increased maternal liver Cd+2 concentrations (364 µg/kg) similar to concentrations found in non-occupationally exposed human liver. At gestational day (GD) 18, placental Cd and manganese concentrations were significantly increased in exposed males and females, and zinc was significantly decreased in females. Placental efficiency was significantly decreased in GD18-exposed males. Increases in hepatic Cd concentrations and a transient prenatal increase in zinc were observed in exposed female liver. Fetal and adult liver iron concentrations were decreased in both sexes, and decreases in hepatic zinc, iron, and manganese were observed in exposed females. Analysis of GD18 placental and liver metallothionein mRNA expression revealed significant Cd-induced upregulation of placental metallothionein in both sexes, and a significant decrease in fetal hepatic metallothionein in exposed females. In placenta, expression of metal ion transporters responsible for metal ion uptake was increased in exposed females. In liver of exposed adult female offspring, expression of the divalent cation importer (Slc39a14/Zip14) decreased, whereas expression of the primary exporter (Slc30a10/ZnT10) increased. These findings demonstrate that Cd can preferentially cross the female placenta, accumulate in the liver, and cause lifelong dysregulation of metal ion concentrations associated with metabolic disruption. DA - 2022/2/25/ PY - 2022/2/25/ DO - 10.1093/toxsci/kfac027 VL - 2 SP - SN - 1096-0929 UR - https://doi.org/10.1093/toxsci/kfac027 KW - gestation KW - epigenetic KW - essential metals KW - metallothionein KW - placenta ER - TY - JOUR TI - Utilizing Pine Needles to Temporally and Spatially Profile Per- and Polyfluoroalkyl Substances (PFAS) AU - Kirkwood, Kaylie I AU - Fleming, Jonathon AU - Nguyen, Helen AU - Reif, David M. AU - Baker, Erin S. AU - Belcher, Scott M. T2 - ENVIRONMENTAL SCIENCE & TECHNOLOGY AB - As concerns over exposure to per- and polyfluoroalkyl substances (PFAS) are continually increasing, novel methods to monitor their presence and modifications are greatly needed, as some have known toxic and bioaccumulative characteristics while most have unknown effects. This task however is not simple, as the Environmental Protection Agency (EPA) CompTox PFAS list contains more than 9000 substances as of September 2020 with additional substances added continually. Nontargeted analyses are therefore crucial to investigating the presence of this immense list of possible PFAS. Here, we utilized archived and field-sampled pine needles as widely available passive samplers and a novel nontargeted, multidimensional analytical method coupling liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) to evaluate the temporal and spatial presence of numerous PFAS. Over 70 PFAS were detected in the pine needles from this study, including both traditionally monitored legacy perfluoroalkyl acids (PFAAs) and their emerging replacements such as chlorinated derivatives, ultrashort chain PFAAs, perfluoroalkyl ether acids including hexafluoropropylene oxide dimer acid (HFPO-DA, "GenX") and Nafion byproduct 2, and a cyclic perfluorooctanesulfonic acid (PFOS) analog. Results from this study provide critical insight related to PFAS transport, contamination, and reduction efforts over the past six decades. DA - 2022/3/15/ PY - 2022/3/15/ DO - 10.1021/acs.est.1c06483 VL - 56 IS - 6 SP - 3441-3451 SN - 1520-5851 UR - https://doi.org/10.1021/acs.est.1c06483 KW - Biomonitoring KW - contamination KW - per- and polyfluoroalkyl substances KW - fluoroethers KW - ion mobility KW - mass spectrometry KW - PFAS ER - TY - JOUR TI - Implementation of Zebrafish Ontologies for Toxicology Screening T2 - Frontiers in Toxicology AB - 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. DA - 2022/// PY - 2022/// DO - 10.3389/ftox.2022.817999 UR - https://www.frontiersin.org/articles/10.3389/ftox.2022.817999/abstract ER - TY - JOUR TI - Mass Spectrometry Imaging of N-Linked Glycans in a Formalin-Fixed Paraffin-Embedded Human Prostate by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization AU - Pace, Crystal L. AU - Angel, Peggi M. AU - Drake, Richard R. AU - Muddiman, David C. T2 - JOURNAL OF PROTEOME RESEARCH AB - N-Linked glycans are structurally diverse polysaccharides that represent significant biological relevance due to their involvement in disease progression and cancer. Due to their complex nature, N-linked glycans pose many analytical challenges requiring the continued development of analytical technologies. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is a hybrid ionization technique commonly used for mass spectrometry imaging (MSI) applications. Previous work demonstrated IR-MALDESI to significantly preserve sialic acid containing N-linked glycans that otherwise require chemical derivatization prior to detection. Here, we demonstrate the first analysis of N-linked glycans in situ by IR-MALDESI MSI. A formalin-fixed paraffin-embedded human prostate tissue was analyzed in negative ionization mode after tissue washing, antigen retrieval, and pneumatic application of PNGase F for enzymatic digestion of N-linked glycans. Fifty-three N-linked glycans were confidently identified in the prostate sample where more than 60% contained sialic acid residues. This work demonstrates the first steps in N-linked glycan imaging of biological tissues by IR-MALDESI MSI. Raw data files are available in MassIVE (identifier: MSV000088414). DA - 2022/1/7/ PY - 2022/1/7/ DO - 10.1021/acs.jproteome.1c00822 VL - 21 IS - 1 SP - 243-249 SN - 1535-3907 KW - IR-MALDESI KW - N-linked glycans KW - mass spectrometry imaging KW - prostate cancer ER - TY - JOUR TI - Phosphorylation-dependent proteome of Marcks in ependyma during aging and behavioral homeostasis in the mouse forebrain AU - Muthusamy, Nagendran AU - Williams, Taufika I AU - O'Toole, Ryan AU - Brudvig, Jon J. AU - Adler, Kenneth B. AU - Weimer, Jill M. AU - Muddiman, David C. AU - Ghashghaei, H. Troy T2 - GEROSCIENCE AB - Ependymal cells (ECs) line the ventricular surfaces of the mammalian central nervous system (CNS) and their development is indispensable to structural integrity and functions of the CNS. We previously reported that EC-specific genetic deletion of the myristoylated alanine-rich protein kinase C substrate (Marcks) disrupts barrier functions and elevates oxidative stress and lipid droplet accumulation in ECs causing precocious cellular aging. However, little is known regarding the mechanisms that mediate these changes in ECs. To gain insight into Marcks-mediated mechanisms, we performed mass spectrometric analyses on Marcks-associated proteins in young and aged ECs in the mouse forebrain using an integrated approach. Network analysis on annotated proteins revealed that the identified Marcks-associated complexes are in part involved in protein transport mechanisms in young ECs. In fact, we found perturbed intracellular vesicular trafficking in cultured ECs with selective deletion of Marcks (Marcks-cKO mice), or upon pharmacological alteration to phosphorylation status of Marcks. In comparison, Marcks-associated protein complexes in aged ECs appear to be involved in regulation of lipid metabolism and responses to oxidative stress. Confirming this, we found elevated signatures of inflammation in the cerebral cortices and the hippocampi of young Marcks-cKO mice. Interestingly, behavioral testing using a water maze task indicated that spatial learning and memory is diminished in young Marcks-cKO mice similar to aged wildtype mice. Taken together, our study provides first line of evidence for potential mechanisms that may mediate differential Marcks functions in young and old ECs, and their effect on forebrain homeostasis during aging. DA - 2022/1/24/ PY - 2022/1/24/ DO - 10.1007/s11357-022-00517-3 VL - 1 SP - SN - 2509-2723 KW - Aging KW - Behavior KW - Clca3 KW - Ependymal cells KW - Forebrain KW - Marcks KW - Mass spectrometry KW - Neuroinflammation ER - TY - JOUR TI - Analysis of per- and polyfluoroalkyl substances in Houston Ship Channel and Galveston Bay following a large-scale industrial fire using ion-mobility-spectrometry-mass spectrometry AU - Valdiviezo, Alan AU - Aly, Noor A. AU - Luo, Yu-Syuan AU - Cordova, Alexandra AU - Casillas, Gaston AU - Foster, MaKayla AU - Baker, Erin S. AU - Rusyn, Ivan T2 - JOURNAL OF ENVIRONMENTAL SCIENCES AB - Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants of concern because of their ubiquitous presence in surface and ground water; analytical methods that can be used for rapid comprehensive exposure assessment and fingerprinting of PFAS are needed. Following the fires at the Intercontinental Terminals Company (ITC) in Deer Park, TX in 2019, large quantities of PFAS-containing firefighting foams were deployed. The release of these substances into the Houston Ship Channel/Galveston Bay (HSC/GB) prompted concerns over the extent and level of PFAS contamination. A targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based study of temporal and spatial patterns of PFAS associated with this incident revealed presence of 7 species; their levels gradually decreased over a 6-month period. Because the targeted LC-MS/MS analysis was focused on about 30 PFAS molecules, it may have missed other PFAS compounds present in firefighting foams. Therefore, we utilized untargeted LC-ion mobility spectrometry-mass spectrometry (LC-IMS-MS)-based analytical approach for a more comprehensive characterization of PFAS in these water samples. We analyzed 31 samples from 9 sites in the HSC/GB that were collected over 5 months after the incident. Our data showed that additional 19 PFAS were detected in surface water of HSC/GB, most of them decreased gradually after the incident. PFAS features detected by LC-MS/MS correlated well in abundance with LC-IMS-MS data; however, LC-IMS-MS identified a number of additional PFAS, many known to be components of firefighting foams. These findings therefore illustrate that untargeted LC-IMS-MS improved our understanding of PFAS presence in complex environmental samples. DA - 2022/5// PY - 2022/5// DO - 10.1016/j.jes.2021.08.004 VL - 115 SP - 350-362 SN - 1878-7320 KW - Emergency KW - Environmental disaster KW - PFAS ER - TY - JOUR TI - On the relationship between extant innate immune receptors and the evolutionary origins of jawed vertebrate adaptive immunity AU - Dornburg, Alex AU - Yoder, Jeffrey A. T2 - IMMUNOGENETICS DA - 2022/1/4/ PY - 2022/1/4/ DO - 10.1007/s00251-021-01232-7 VL - 74 IS - 1 SP - SN - 1432-1211 UR - https://doi.org/10.1007/s00251-021-01232-7 KW - Bowfin and gar (Holostei) KW - Immune system evolution KW - Joining domains KW - Origins of V(D)J recombination KW - Zebrafish ER - TY - JOUR TI - Environmental exposures contribute to respiratory and allergic symptoms among women living in the banana growing regions of Costa Rica AU - Alhanti, Brooke AU - Joode, Berna AU - Martinez, Manuel Soto AU - Mora, Ana M AU - Gamboa, Leonel Córdoba AU - Reich, Brian AU - Lindh, Christian H AU - Lépiz, Marcela Quirós AU - Hoppin, Jane A T2 - Occupational and Environmental Medicine AB - Objectives This research evaluates whether environmental exposures (pesticides and smoke) influence respiratory and allergic outcomes in women living in a tropical, agricultural environment. Methods We used data from 266 mothers from the Infants’ Environmental Health cohort study in Costa Rica. We evaluated environmental exposures in women by measuring seven pesticide and two polycyclic aromatic hydrocarbons metabolites in urine samples. We defined ‘high exposure’ as having a metabolite value in the top 75th percentile. We collected survey data on respiratory and allergic outcomes in mothers as well as on pesticides and other environmental exposures. Using logistic regression models adjusted for obesity, we assessed the associations of pesticide exposure with multiple outcomes (wheeze, doctor-diagnosed asthma, high (≥2) asthma score based on symptoms, rhinitis, eczema and itchy rash). Results Current pesticide use in the home was positively associated with diagnosed asthma (OR=1.99 (95% CI=1.05 to 3.87)). High urinary levels of 5-hydroxythiabendazole (thiabendazole metabolite) and living in a neighbourhood with frequent smoke from waste burning were associated with a high asthma score (OR=1.84 (95%CI=1.05 to 3.25) and OR=2.31 (95%CI=1.11 to 5.16), respectively). Women who worked in agriculture had a significantly lower prevalence of rhinitis (0.19 (0.01 to 0.93)), but were more likely to report eczema (OR=2.54 (95%CI=1.33 to 4.89)) and an itchy rash (OR=3.17 (95%CI=1.24 to 7.73)). Conclusions While limited by sample size, these findings suggest that environmental exposure to both pesticides and smoke may impact respiratory and skin-related allergic outcomes in women. DA - 2022/7// PY - 2022/7// DO - 10.1136/oemed-2021-107611 UR - https://doi.org/10.1136/oemed-2021-107611 KW - asthma KW - respiratory disease KW - allergy KW - pesticide KW - agriculture ER - TY - JOUR TI - The evolution of innate immune receptors: investigating the diversity, distribution, and phylogeny of immune recognition across eukaryotes AU - Buckley, Katherine M. AU - Yoder, Jeffrey A. T2 - Immunogenetics DA - 2022/2// PY - 2022/2// DO - 10.1007/s00251-021-01243-4 VL - 74 IS - 1 SP - 1-4 UR - https://doi.org/10.1007/s00251-021-01243-4 ER -