TY - CHAP TI - Nuclear receptors AU - Kullman, S.W. AU - Baldwin, W.B. AU - LeBlanc, G.A. T2 - Molecular and Biochemical Toxicology A2 - Smart, Robert C. A2 - Hodgson, Ernest PY - 2018/// ET - 5th SP - 293–326 PB - John Wiley & Sons ER - TY - BOOK TI - Molecular and Biochemical Toxicology DA - 2018/// PY - 2018/// ET - 5th PB - J. Wiley and Sons ER - TY - BOOK TI - Molecular and Biochemical Toxicology A3 - Smart, R.C. A3 - Hodgson, E. DA - 2018/// PY - 2018/// ET - 5th PB - J. Wiley and Sons ER - TY - CHAP TI - Carcinogenesis AU - Smart, R.C. AU - Hall, J.R. T2 - Molecular and Biochemical Toxicology A2 - Smart, R.C. A2 - Hodgson, E. PY - 2018/// ET - 5th PB - J Wiley and Sons ER - TY - CHAP TI - Molecular Techniques in the Study of Gene Function AU - Tsuji, Y. AU - Smart, R.C. T2 - Molecular and Biochemical Toxicology A2 - Smart, R.C. A2 - Hodgson, E. PY - 2018/// ET - 5th PB - J Wiley and Sons ER - TY - CHAP TI - Molecular and Biochemical Toxicology: Definition and Scope AU - Smart, R.C. AU - Hodgson, E. T2 - Molecular and Biochemical Toxicology A2 - Smart, R.C. A2 - Hodgson, E. PY - 2018/// ET - 5th PB - J Wiley and Sons ER - TY - SOUND TI - Laboratory testing for Heat Generation Potential and Applications to Field Conditions AU - Barlaz, M.A. AU - Jafari, N. DA - 2018/11/7/ PY - 2018/11/7/ ER - TY - SOUND TI - Biological and Chemical Reactions Contributing to Heat Generation in Landfills: Current Research and Model Simulations AU - Barlaz, M.A. AU - Benson, C.H. DA - 2018/// PY - 2018/// PB - Research and Edcn. Fndn ER - TY - CONF TI - So you want to publish a peer-reviewed journal article on LCA: What are the expectations and what are reviewers looking for? AU - Barlaz, M.A. AU - Arena, U. AU - Damgaard, A. T2 - 2nd Conference on Life Cycle Assessment of Waste C2 - 2018/// CY - Technical University of Denmark DA - 2018/// PY - 2018/6/18/ ER - TY - RPRT TI - Development of Methods to Measure the Hydrogen Sulfide Production Potential of Sulfur-Containing Wastes AU - Sun, M. AU - Sun, W. AU - Barlaz, M.A. A3 - Environmental Research and Education Foundation DA - 2018/// PY - 2018/// PB - Environmental Research and Education Foundation ER - TY - CONF TI - Design of Waste Transfer Station Concrete Overlays Against Premature Deterioration AU - Park, S. AU - Castellano, L. AU - Pour-Ghaz, M. AU - Barlaz, M.A. T2 - SC Solid Waste Association of North America Annual Meeting C2 - 2018/// CY - Charleston, SC DA - 2018/// PY - 2018/11/5/ ER - TY - CONF TI - How Do We Address Data Quality in LCA of Waste Technologies AU - Damgaard, A. AU - Henriksen, T. AU - Levis, J.W. AU - Barlaz, M.A. T2 - 2nd Conference on Life Cycle Assessment of Waste C2 - 2018/// CY - Technical University of Denmark DA - 2018/// PY - 2018/6/18/ ER - TY - CONF TI - Multistage Life-Cycle Optimization for Developing and Evaluating Current and Future Solid Waste Systems AU - Levis, J.W. AU - Barlaz, M.A. T2 - 2nd Conference on Life Cycle Assessment of Waste C2 - 2018/// CY - Technical University of Denmark DA - 2018/// PY - 2018/6/18/ ER - TY - CONF TI - Life-Cycle Model Development and Transparency: Challenges and Choices AU - Barlaz, M.A. AU - Levis, J.W. T2 - 2nd Conference on Life Cycle Assessment of Waste C2 - 2018/// CY - Technical University of Denmark DA - 2018/// PY - 2018/6/18/ ER - TY - CONF TI - The Effect of Organic Acids on the Abrasion Resistance of Cementitious Materials AU - Park, S. AU - Pour-Ghaz, M. AU - Castellano, L. AU - Barlaz, M. T2 - 9th Advances in Cement-Based Materials C2 - 2018/// CY - State College, PA DA - 2018/// PY - 2018/6/11/ ER - TY - CONF TI - Life Cycle Modeling for Future Solid Waste Management Planning AU - Levis, J.W. AU - Jaunich, M.K. AU - Barlaz, M.A. T2 - Global Waste Management Symposium C2 - 2018/// CY - Indian Wells, CA DA - 2018/// PY - 2018/2/11/ ER - TY - CONF TI - Heat Generation and Accumulation in Municipal Solid Waste Landfills AU - Hao, Z. AU - Ducoste, J. AU - Barlaz, M.A. T2 - Global Waste Management Symposium C2 - 2018/// CY - Indian Wells, CA DA - 2018/// PY - 2018/2/11/ ER - TY - CONF TI - Microbial Population Development during the Anaerobic decomposition of Food Waste AU - Lee., E. AU - de los Reyes, F.L. AU - Barlaz, M.A. T2 - Global Waste Management Symposium C2 - 2018/// CY - Indian Wells, CA DA - 2018/// PY - 2018/2/11/ ER - TY - JOUR TI - Cadmium Disrupts Vestibular Function by Interfering with Otolith Formation T2 - BioRXiv AB - Abstract Cadmium (Cd 2+ ) is a transition metal found ubiquitously in the earth’s crust and is extracted in the production of other metals such as copper, lead, and zinc 1,2 . Human exposure to Cd 2+ occurs through food consumption, cigarette smoking, and the combustion of fossil fuels. Cd 2+ has been shown to be nephrotoxic, neurotoxic, and osteotoxic, and is a known carcinogen. Animal studies and epidemiological studies have linked prenatal Cd 2+ exposure to hyperactivity and balance disorders although the mechanisms remain unknown. In this study we show that zebrafish developmentally exposed to Cd 2+ exhibit abnormal otolith development and show an increased tendency to swim in circles, observations that are consistent with an otolith-mediated vestibular defect, in addition to being hyperactive. We also demonstrate that the addition of calcium rescues otolith malformation and reduces circling behavior but has no ameliorating effect on hyperactivity, suggesting that hyperactivity and balance disorders in human populations exposed to Cd are manifestations of separate underlying molecular pathways. DA - 2018/// PY - 2018/// DO - 10.1101/162347 ER - TY - JOUR TI - Characterizing sources of variability in zebrafish embryo screening protocols. AU - Hamm, Jon T. AU - Ceger, Patricia AU - Allen, David AU - Stout, Matt AU - Maull, Elizabeth A. AU - Baker, Greg AU - Zmarowski, Amy AU - Padilla, Stephanie AU - Perkins, Edward AU - Planchart, Antonio AU - Stedman, Donald AU - Tal, Tamara AU - Tanguay, Robert L. AU - Volz, David C. AU - Wilbanks, Mitch S. AU - Walker, Nigel J. T2 - ALTEX AB - There is a need for fast, efficient, and cost-effective hazard identification and characterization of chemical hazards. This need is generating increased interest in the use of zebrafish embryos as both a screening tool and an alternative to mammalian test methods. A Collaborative Workshop on Aquatic Models and 21st Century Toxicology identified the lack of appropriate and consistent testing protocols as a challenge to the broader application of the zebrafish embryo model. The National Toxicology Program established the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) initiative to address the lack of consistent testing guidelines and identify sources of variability for zebrafish-based assays. This report summarizes initial SEAZIT information-gathering efforts. Investigators in academic, government, and industry laboratories that routinely use zebrafish embryos for chemical toxicity testing were asked about their husbandry practices and standard protocols. Information was collected about protocol components including zebrafish strains, feed, system water, disease surveillance, embryo exposure conditions, and endpoints. Literature was reviewed to assess issues raised by the investigators. Interviews revealed substantial variability across design parameters, data collected, and analysis procedures. The presence of the chorion and renewal of exposure media (static versus static-renewal) were identified as design parameters that could potentially influence study outcomes and should be investigated further with studies to determine chemical uptake from treatment solution into embryos. The information gathered in this effort provides a basis for future SEAZIT activities to promote more consistent practices among researchers using zebrafish embryos for toxicity evaluation. DA - 2018/// PY - 2018/// DO - 10.14573/altex.1804162 VL - 36 IS - 1 SP - 103–120 UR - https://doi.org/10.14573/altex.1804162 ER - TY - JOUR TI - CLARITY-BPA: Heart (Belcher) AU - Belcher, Scott T2 - Chemical Effects in Biological Systems (CEBS) DA - 2018/8// PY - 2018/8// DO - 10.22427/ntp-data-018-00016-0001-000-7 ER - TY - RPRT TI - Evaluation of cVOC Removal Efficiencies by Various Technologies AU - Cotton, C. AU - Collins, J. AU - Knappe, D.R.U. AU - Linden, K. AU - Brown, J. AU - Upadhyaya, G. AU - Ponturo, P. A3 - Water Research Foundation DA - 2018/// PY - 2018/// M1 - 4492 M3 - Executive Summary PB - Water Research Foundation SN - 4492 ER - TY - BOOK TI - Ecotoxicology Essentials: Environmental Contaminants and Their Biological Effects on Animals and Plants. By Donald W. Sparling. Academic Press. Amsterdam (The Netherlands) and Boston (Massachusetts): Elsevier. $79.95 (paper). ix + 490 p.; ill.; index. ISBN: 978-0-12-801947-4. 2016. AU - Buchwalter, David B. AU - Sparling, Donald W. AB - Previous articleNext article No AccessEcologyEcotoxicology Essentials: Environmental Contaminants and Their Biological Effects on Animals and Plants. By Donald W. Sparling. Academic Press. Amsterdam (The Netherlands) and Boston (Massachusetts): Elsevier. $79.95 (paper). ix + 490 p.; ill.; index. ISBN: 978-0-12-801947-4. 2016.David B. BuchwalterDavid B. BuchwalterBiological Sciences, North Carolina State University, Raleigh, North Carolina Search for more articles by this author Biological Sciences, North Carolina State University, Raleigh, North CarolinaPDFPDF PLUSFull Text Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by The Quarterly Review of Biology Volume 93, Number 1March 2018 Published in association with Stony Brook University Article DOIhttps://doi.org/10.1086/696739 Views: 66Total views on this site For permission to reuse, please contact [email protected]PDF download Crossref reports no articles citing this article. DA - 2018/3// PY - 2018/3// DO - 10.1086/696739 VL - 93 PB - University of Chicago Press SE - 29–29 UR - http://dx.doi.org/10.1086/696739 ER - TY - JOUR TI - Why adult mayflies of Cloeon dipterum (Ephemeroptera:Baetidae) become smaller as temperature warms AU - Sweeney, Bernard W. AU - Funk, David H. AU - Camp, Allison A. AU - Buchwalter, David B. AU - Jackson, John K. T2 - Freshwater Science AB - We reared Cloeon dipterum from egg hatch to adult at 10 constant temperatures (12.1–33.5°C) to test 3 hypotheses (thermal equilibrium hypothesis, temperature size rule [TSR], and O2- and capacity-limited thermal tolerance [OCLTT]) that account for variation in life-history traits across thermal gradients. Male and female adult size declined ~67 and 78% and larval development time declined ~88% with warming; chronic survivorship (thermal limit for population growth) was highest from 16.2 to 23.9°C (mean = 85%) and declined to 0 at 33.5°C; thresholds for 0 growth and development were 10.0 and 10.7°C, respectively; peak rate of population increase (r) occurred at 27.8°C; rates of growth and development were maximal at 30°C; fecundity was greatest at 12.1°C; and between 14.3 and 30°C, growth and development rates increased linearly and the number of degree days (>10.7°C) to complete development was nearly constant (mean = 271). Acute survivorship during short-term thermal ramping was 0 at 40°C. Warming temperature caused development rate to increase proportionately faster than growth rate; male and female adult size to decrease as per TSR, with adult females ~5× larger at 12.1 than 31.7°C; adult size to decrease proportionately more for females than males; and fecundity to decrease proportionately more than adult female size. TSR was related to differences in the responses of growth and development rates at temperatures above thresholds rather than to thresholds for growth or development per se. Respirometry suggested that OCLTT is more applicable to acute than chronic thermal limits. Cloeon dipterum appears to have a thermal ‘acclimation zone’ between 14.3 and 30°C where development and growth rates change linearly and degree-day requirements to complete metamorphosis are constant. The optimum temperature is ~27.8°C where r is maximum. We propose 5 hypotheses to explain these patterns. DA - 2018/3// PY - 2018/3// DO - 10.1086/696611 VL - 37 IS - 1 SP - 64-81 J2 - Freshwater Science LA - en OP - SN - 2161-9549 2161-9565 UR - http://dx.doi.org/10.1086/696611 DB - Crossref KW - temperature KW - growth KW - development KW - fecundity KW - respiration KW - aquatic insect KW - aerobic scope ER - TY - JOUR TI - Characterization of the Spectral Accuracy of an Orbitrap Mass Analyzer Using Isotope Ratio Mass Spectrometry AU - Khodjaniyazova, Sitora AU - Nazari, Milad AU - Garrard, Kenneth P. AU - Matos, Mayara P. V. AU - Jackson, Glen P. AU - Muddiman, David C. T2 - Analytical Chemistry AB - Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source coupled to the Q Exactive Plus has been extensively used in untargeted mass spectrometry imaging (MSI) analyses of biological tissue sections. Although the Orbitrap is a high-resolution and accurate-mass (HRAM) mass analyzer, these attributes alone cannot be used for the reliable identification of unknown analytes observed in complex biological matrices. Spectral accuracy (SA) is the ability of the mass spectrometer to accurately measure the isotopic distributions which, when used with high mass measurement accuracy (MMA), can facilitate the elucidation of a single elemental composition. To investigate the effects of different ion populations on an Orbitrap’s SA and MMA, a solution of caffeine, the tetrapeptide MRFA, and ultramark was analyzed using a Q Exactive Plus across eight distinct automatic gain control (AGC) targets. The same compounds from the same lot numbers were also individually analyzed using isotope ratio mass spectrometry (IRMS) to accurately determine the isotopic abundance of 13C, 15N, and 34S. We demonstrated that at optimum absolute ion abundances the Orbitrap can be used to accurately count carbons, nitrogens, and sulfurs in samples with varying masses. Additionally, absolute monoisotopic ion abundances required for high SA were empirically determined by using the expected (IRMS) and experimental (Orbitrap) isotopic distributions to calculate the Pearson chi-square test. These thresholds for absolute ion abundances can be used in untargeted MSI studies to shorten an identification list by rapidly screening for isotopic distributions whose absolute ion abundances are high enough to accurately estimate the number of atoms. DA - 2018/1/11/ PY - 2018/1/11/ DO - 10.1021/ACS.ANALCHEM.7B03983 VL - 90 IS - 3 SP - 1897-1906 J2 - Anal. Chem. LA - en OP - SN - 0003-2700 1520-6882 UR - http://dx.doi.org/10.1021/ACS.ANALCHEM.7B03983 DB - Crossref ER - TY - JOUR TI - Jürgen H. Gross: Mass spectrometry: a textbook, 3rd ed. AU - Muddiman, David C. T2 - Analytical and Bioanalytical Chemistry DA - 2018/2/7/ PY - 2018/2/7/ DO - 10.1007/S00216-018-0870-8 VL - 410 IS - 8 SP - 2051-2052 J2 - Anal Bioanal Chem LA - en OP - SN - 1618-2642 1618-2650 UR - http://dx.doi.org/10.1007/S00216-018-0870-8 DB - Crossref ER - TY - JOUR TI - C/EBPβ deletion in oncogenic Ras skin tumors is a synthetic lethal event AU - Messenger, Zachary J. AU - Hall, Jonathan R. AU - Jima, Dereje D. AU - House, John S. AU - Tam, Hann W. AU - Tokarz, Debra A. AU - Smart, Robert C. T2 - Cell Death & Disease AB - Therapeutic targeting of specific genetic changes in cancer has proven to be an effective therapy and the concept of synthetic lethality has emerged. CCAAT/enhancer-binding protein-β (C/EBPβ), a basic leucine zipper transcription factor, has important roles in cellular processes including differentiation, inflammation, survival, and energy metabolism. Using a genetically engineered mouse model, we report that the deletion C/EBPβ in pre-existing oncogenic Ha-Ras mouse skin tumors in vivo resulted in rapid tumor regression. Regressing tumors exhibited elevated levels of apoptosis and p53 protein/activity, while adjacent C/EBPβ-deleted skin did not. These results indicate that the deletion of C/EBPβ de-represses p53 in oncogenic Ras tumors but not in normal wild-type Ras keratinocytes, and that C/EBPβ is essential for survival of oncogenic Ras tumors. Co-deletion of C/EBPβ and p53 in oncogenic Ras tumors showed p53 is required for tumor regression and elevated apoptosis. In tumors, loss of a pathway that confers adaptability to a stress phenotype of cancer/tumorigenesis, such as DNA damage, could result in selective tumor cell killing. Our results show that oncogenic Ras tumors display a significant DNA damage/replicative stress phenotype and these tumors have acquired a dependence on C/EBPβ for their survival. RNAseq data analysis of regressing tumors deleted of C/EBPβ indicates a novel interface between p53, type-1 interferon response, and death receptor pathways, which function in concert to produce activation of extrinsic apoptosis pathways. In summary, the deletion of C/EBPβ in oncogenic Ras skin tumors is a synthetic lethal event, making it a promising target for future potential anticancer therapies. DA - 2018/10/15/ PY - 2018/10/15/ DO - 10.1038/S41419-018-1103-Y VL - 9 IS - 11 J2 - Cell Death Dis LA - en OP - SN - 2041-4889 UR - http://dx.doi.org/10.1038/S41419-018-1103-Y DB - Crossref ER - TY - ER - TY - JOUR TI - Evaluation of Waste Eggshells for Adsorption of Copper from Synthetic and Swine Wastewater AU - Hess, Brianna J. AU - Kolar, Praveen AU - Classen, John J. AU - Knappe, Detlef AU - Cheng, Jay J. T2 - Transactions of the ASABE AB - Abstract. Biomass-derived adsorbents are an attractive alternative to conventional water treatment methods. This study evaluated eggshells produced by the liquid egg and food processing industry for the adsorption of copper from aqueous systems. Research objectives were to (1) determine copper adsorption mechanisms and (2) evaluate copper adsorption by eggshells for the treatment of wastewater. Batch experiments were performed by contacting eggshells with copper solutions to obtain equilibrium, kinetic, and thermodynamic data to determine removal mechanisms and maximum adsorption capacity. Results suggested that the adsorption of copper followed a second-order kinetic model with a theoretical maximum adsorption capacity of 4.3 mg g -1 (20°C). In addition, eggshell adsorption was found to be a favorable process, with an activation energy of approximately 27 to 29 kJ mol -1 , and followed similar mechanisms as its calcite analog. Data indicated that slightly acidic (pH = 6) to near-neutral pH conditions enhanced adsorption of copper. Additional experiments were performed using swine lagoon wastewater to evaluate the efficacy of eggshells to treat copper from lagoon wastewater. The data suggested that unmodified eggshells were effective for application in swine lagoon systems only under acidic conditions (pH = 4). Further research is needed to modify eggshells that can adsorb copper in lagoon wastewater at neutral and alkaline pH. Keywords: Adsorption, Copper, Eggshell, Swine lagoon, Water. DA - 2018/// PY - 2018/// DO - 10.13031/trans.12599 VL - 61 IS - 3 SP - 967-976 LA - en OP - SN - 2151-0040 UR - http://dx.doi.org/10.13031/trans.12599 DB - Crossref KW - Adsorption KW - Copper KW - Eggshell KW - Swine lagoon KW - Water ER - TY - JOUR TI - Recently Detected Drinking Water Contaminants: GenX and Other Per- and Polyfluoroalkyl Ether Acids AU - Hopkins, Zachary R. AU - Sun, Mei AU - DeWitt, Jamie C. AU - Knappe, Detlef R.U. T2 - Journal - American Water Works Association AB - For several decades, a common processing aid in the production of fluoropolymers was the ammonium salt of perfluorooctanoic acid (PFOA). Because PFOA is persistent, bioaccumulative, and toxic, its production and use are being phased out in the United States. In 2009, the US Environmental Protection Agency stipulated conditions for the manufacture and commercial use of GenX, a PFOA replacement. While GenX is produced for commercial purposes, the acid form of GenX is also generated as a byproduct during the production of fluoromonomers. The discovery of high concentrations of GenX and related perfluoroalkyl ether acids (PFEAs) in the Cape Fear River and in finished drinking water of more than 200,000 North Carolina residents required quick action by researchers, regulators, public health officials, commercial laboratories, drinking water providers, and consulting engineers. Information about sources and toxicity of GenX as well as an analytical method for the detection of GenX and eight related PFEAs is presented. GenX/PFEA occurrence in water and GenX/PFEA removal by different drinking water treatment processes are also discussed. DA - 2018/6/14/ PY - 2018/6/14/ DO - 10.1002/awwa.1073 VL - 110 IS - 7 SP - 13-28 J2 - Journal - American Water Works Association LA - en OP - SN - 0003-150X UR - http://dx.doi.org/10.1002/awwa.1073 DB - Crossref KW - emerging per- and polyfluoroalkyl substances KW - hexafluoropropylene oxide dimer acid (HFPO-DA) KW - Nafion by-products KW - industrial wastewater KW - unregulated contaminants ER - TY - JOUR TI - Methods of Responsibly Managing End-of-Life Foams and Plastics Containing Flame Retardants: Part I AU - Lucas, Donald AU - Petty, Sara M. AU - Keen, Olya AU - Luedeka, Bob AU - Schlummer, Martin AU - Weber, Roland AU - Barlaz, Morton AU - Yazdani, Ramin AU - Riise, Brian AU - Rhodes, James AU - Nightingale, Dave AU - Diamond, Miriam L. AU - Vijgen, John AU - Lindeman, Avery AU - Blum, Arlene AU - Koshland, Catherine P. T2 - Environmental Engineering Science AB - Flame retardants (FRs) are added to foams and plastics to comply with flammability standards and test requirements in products for household and industrial uses. When these regulations were implemented, potential health and environmental impacts of FR use were not fully recognized or understood. Extensive research in the past decades reveal that exposure to halogenated FRs, such as those used widely in furniture foam, is associated with and/or causally related to numerous health effects in animals and humans. While many of the toxic FRs have been eliminated and replaced by other FRs, existing products containing toxic or potentially toxic chemical FRs will remain in use for decades, and new products containing these and similar chemicals will permeate the environment. When such products reach the end of their useful life, proper disposal methods are needed to avoid health and ecological risks. To minimize continued human and environmental exposures to hazardous FR chemicals from discarded products, waste management technologies and processes must be improved. This review discusses a wide range of issues associated with all aspects of the use and responsible disposal of wastes containing FRs, and identifies basic and applied research needs in the areas of responsible collection, pretreatment, processing, and management of these wastes. DA - 2018/6// PY - 2018/6// DO - 10.1089/ees.2017.0147 VL - 35 IS - 6 SP - 573-587 J2 - Environmental Engineering Science LA - en OP - SN - 1557-9018 UR - http://dx.doi.org/10.1089/ees.2017.0147 DB - Crossref KW - disposal KW - flame retardants KW - foams KW - plastics ER - TY - JOUR TI - Online Ozonolysis Combined with Ion Mobility-Mass Spectrometry Provides a New Platform for Lipid Isomer Analyses AU - Poad, B.L.J. AU - Zheng, X. AU - Mitchell, T.W. AU - Smith, R.D. AU - Baker, E.S. AU - Blanksby, S.J. T2 - Analytical Chemistry AB - One of the most significant challenges in contemporary lipidomics lies in the separation and identification of lipid isomers that differ only in site(s) of unsaturation or geometric configuration of the carbon–carbon double bonds. While analytical separation techniques including ion mobility spectrometry (IMS) and liquid chromatography (LC) can separate isomeric lipids under appropriate conditions, conventional tandem mass spectrometry cannot provide unequivocal identification. To address this challenge, we have implemented ozone-induced dissociation (OzID) in-line with LC, IMS, and high resolution mass spectrometry. Modification of an IMS-capable quadrupole time-of-flight mass spectrometer was undertaken to allow the introduction of ozone into the high-pressure trapping ion funnel region preceding the IMS cell. This enabled the novel LC-OzID-IMS-MS configuration where ozonolysis of ionized lipids occurred rapidly (10 ms) without prior mass-selection. LC-elution time alignment combined with accurate mass and arrival time extraction of ozonolysis products facilitated correlation of precursor and product ions without mass-selection (and associated reductions in duty cycle). Unsaturated lipids across 11 classes were examined using this workflow in both positive and negative ion modalities, and in all cases, the positions of carbon–carbon double bonds were unequivocally assigned based on predictable OzID transitions. Under these conditions, geometric isomers exhibited different IMS arrival time distributions and distinct OzID product ion ratios providing a means for discrimination of cis/trans double bonds in complex lipids. The combination of OzID with multidimensional separations shows significant promise for facile profiling of unsaturation patterns within complex lipidomes including human plasma. DA - 2018/// PY - 2018/// DO - 10.1021/acs.analchem.7b04091 VL - 90 IS - 2 SP - 1292-1300 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85040692961&partnerID=MN8TOARS ER - TY - JOUR TI - Unraveling the isomeric heterogeneity of glycans: Ion mobility separations in structures for lossless ion manipulations AU - Nagy, G. AU - Attah, I.K. AU - Garimella, S.V.B. AU - Tang, K. AU - Ibrahim, Y.M. AU - Baker, E.S. AU - Smith, R.D. T2 - Chemical Communications AB - A new ultrahigh resolution ion mobility platform enables the fast separation and characterization of isomeric glycoforms. DA - 2018/// PY - 2018/// DO - 10.1039/c8cc06966b VL - 54 IS - 83 SP - 11701-11704 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85054888122&partnerID=MN8TOARS ER - TY - JOUR TI - The MPLEx protocol for multi-omic analyses of soil samples AU - Nicora, C.D. AU - Burnum-Johnson, K.E. AU - Nakayasu, E.S. AU - Casey, C.P. AU - White, R.A. AU - Chowdhury, T.R. AU - Kyle, J.E. AU - Kim, Y.-M. AU - Smith, R.D. AU - Metz, T.O. AU - Jansson, J.K. AU - Baker, E.S. T2 - Journal of Visualized Experiments AB - Mass spectrometry (MS)-based integrated metaproteomic, metabolomic, and lipidomic (multi-omic) studies are transforming our ability to understand and characterize microbial communities in environmental and biological systems. These measurements are even enabling enhanced analyses of complex soil microbial communities, which are the most complex microbial systems known to date. Multi-omic analyses, however, do have sample preparation challenges, since separate extractions are typically needed for each omic study, thereby greatly amplifying the preparation time and amount of sample required. To address this limitation, a 3-in-1 method for the simultaneous extraction of metabolites, proteins, and lipids (MPLEx) from the same soil sample was created by adapting a solvent-based approach. This MPLEx protocol has proven to be both simple and robust for many sample types, even when utilized for limited quantities of complex soil samples. The MPLEx method also greatly enabled the rapid multi-omic measurements needed to gain a better understanding of the members of each microbial community, while evaluating the changes taking place upon biological and environmental perturbations. DA - 2018/// PY - 2018/// DO - 10.3791/57343 VL - 2018 IS - 135 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85048523229&partnerID=MN8TOARS KW - Chemistry KW - Issue 135 KW - MPLEx KW - Metaproteomics KW - Lipidomics KW - Metabolomics KW - Multi-omics KW - Mass Spectrometry ER - TY - JOUR TI - Recent advances in lipid separations and structural elucidation using mass spectrometry combined with ion mobility spectrometry, ion-molecule reactions and fragmentation approaches AU - Zheng, X. AU - Smith, R.D. AU - Baker, E.S. T2 - Current Opinion in Chemical Biology AB - Lipids are a vital class of molecules that play important and varied roles in biological processes, however, fully understanding these roles is extremely difficult due to the immense number and diversity of possible lipid species. While recent advances in chromatography and high resolution mass spectrometry have greatly progressed knowledge about distinct lipid species and functions, effectively separating many lipids still remains problematic. Isomeric lipids have made lipid characterization especially difficult and occur due to subclasses having the same chemical composition, or species having multiple acyl chain connectivities (sn-1, sn-2, or sn-3), double bond positions and orientations (cis or trans), and functional group stereochemistries (R versus S). To aid in isomer characterization, ion mobility spectrometry separations, ion-molecule reactions and fragmentation techniques have increasingly been added to lipid analysis workflows. In this manuscript, we review the current state of these approaches and their capabilities for improving the identification of lipid species. DA - 2018/// PY - 2018/// DO - 10.1016/j.cbpa.2017.11.009 VL - 42 SP - 111-118 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85037379449&partnerID=MN8TOARS ER - TY - JOUR TI - Rapid Ion Mobility Separations of Bile Acid Isomers Using Cyclodextrin Adducts and Structures for Lossless Ion Manipulations AU - Chouinard, C.D. AU - Nagy, G. AU - Webb, I.K. AU - Garimella, S.V.B. AU - Baker, E.S. AU - Ibrahim, Y.M. AU - Smith, R.D. T2 - Analytical Chemistry AB - Bile acids (BAs) constitute an important class of steroid metabolites often displaying changes associated with disease states and other health conditions. Current analyses for these structurally similar compounds are limited by a lack of sensitivity and long separation times with often poor isomeric resolution. To overcome these challenges and provide rapid analyses for the BA isomers, we utilized cyclodextrin adducts in conjunction with novel ion mobility (IM) separation capabilities provided by structures for lossless ion manipulations (SLIM). Cyclodextrin was found to interact with both the tauro- and glyco-conjugated BA isomers studied, forming rigid noncovalent host-guest inclusion complexes. Without the use of cyclodextrin adducts, the BA isomers were found to be nearly identical in their respective mobilities and thus unable to be baseline resolved. Each separation of the cyclodextrin-bile acid host-guest inclusion complex was performed in less than 1 s, providing a much more rapid alternative to current liquid chromatography-based separations. SLIM provided capabilities for the accumulation of larger ion populations and IM peak compression that resulted in much higher resolution separations and increased signal intensities for the BA isomers studied. DA - 2018/// PY - 2018/// DO - 10.1021/acs.analchem.8b02990 VL - 90 IS - 18 SP - 11086-11091 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85052280105&partnerID=MN8TOARS ER - TY - JOUR TI - High-throughput serum proteomics for the identification of protein biomarkers of mortality in older men AU - Orwoll, E.S. AU - Wiedrick, J. AU - Jacobs, J. AU - Baker, E.S. AU - Piehowski, P. AU - Petyuk, V. AU - Gao, Y. AU - Shi, T. AU - Smith, R.D. AU - Bauer, D.C. AU - Cummings, S.R. AU - Nielson, C.M. AU - Lapidus, J. T2 - Aging Cell AB - Summary The biological perturbations associated with incident mortality are not well elucidated, and there are limited biomarkers for the prediction of mortality. We used a novel high‐throughput proteomics approach to identify serum peptides and proteins associated with 5‐year mortality in community‐dwelling men age ≥65 years who participated in a longitudinal observational study of musculoskeletal aging (Osteoporotic Fractures in Men: Mr OS ). In a discovery phase, serum specimens collected at baseline in 2473 men were analyzed using liquid chromatography–ion mobility–mass spectrometry, and incident mortality in the subsequent 5 years was ascertained by tri‐annual questionnaire. Rigorous statistical methods were utilized to identify 56 peptides (31 proteins) that were associated with 5‐year mortality. In an independent replication phase, selected reaction monitoring was used to examine 21 of those peptides in baseline serum from 750 additional men; 81% of those peptides remained significantly associated with mortality. Mortality‐associated proteins included a variety involved in inflammation or complement activation; several have been previously linked to mortality (e.g., C‐reactive protein, alpha 1‐antichymotrypsin) and others are not previously known to be associated with mortality. Other novel proteins of interest included pregnancy‐associated plasma protein, VE ‐cadherin, leucine‐rich α‐2 glycoprotein 1, vinculin, vitronectin, mast/stem cell growth factor receptor, and Saa4. A panel of peptides improved the predictive value of a commonly used clinical predictor of mortality. Overall, these results suggest that complex inflammatory pathways, and proteins in other pathways, are linked to 5‐year mortality risk. This work may serve to identify novel biomarkers for near‐term mortality. DA - 2018/// PY - 2018/// DO - 10.1111/acel.12717 VL - 17 IS - 2 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85041307766&partnerID=MN8TOARS KW - aging KW - biomarker KW - inflammation KW - men KW - mortality KW - proteomics ER - TY - JOUR TI - Utilizing Ion Mobility Spectrometry and Mass Spectrometry for the Analysis of Polycyclic Aromatic Hydrocarbons, Polychlorinated Biphenyls, Polybrominated Diphenyl Ethers and Their Metabolites AU - Zheng, X. AU - Dupuis, K.T. AU - Aly, N.A. AU - Zhou, Y. AU - Smith, F.B. AU - Tang, K. AU - Smith, R.D. AU - Baker, E.S. T2 - Analytica Chimica Acta AB - Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants originating from incomplete combustion of organic materials and synthetic sources. PAHs, PCBs, and PBDEs have all been shown to have a significant effect on human health with correlations to cancer and other diseases. Therefore, measuring the presence of these xenobiotics in the environment and human body is imperative for assessing their health risks. To date, their analyses require both gas chromatography and liquid chromatography separations in conjunction with mass spectrometry measurements for detection of both the parent molecules and their hydroxylated metabolites, making their studies extremely time consuming. In this work, we characterized PAHs, PCBs, PBDEs and their hydroxylated metabolites using ion mobility spectrometry coupled with mass spectrometry (IMS-MS) and in combination with different ionization methods including electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI). The collision cross section and m/z trend lines derived from the IMS-MS analyses displayed distinct trends for each molecule type. Additionally, the rapid isomeric and molecular separations possible with IMS-MS showed great promise for quickly distinguishing the parent and metabolized PAH, PCB, and PDBE molecules in complex environmental and biological samples. DA - 2018/12/11/ PY - 2018/12/11/ DO - 10.1016/j.aca.2018.02.054 VL - 1037 SP - 265-273 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85043992934&partnerID=MN8TOARS KW - Ion mobility spectrometry KW - Collision cross section KW - Xenobiotics KW - Polycyclic aromatic hydrocarbons KW - Polychlorinated biphenyls KW - Polybrominated diphenyl ethers KW - Electrospray ionization KW - Atmospheric pressure chemical ionization KW - Atmospheric pressure photoionization ER - TY - JOUR TI - Using Skyline to Analyze Data-Containing Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry Dimensions AU - MacLean, B.X. AU - Pratt, B.S. AU - Egertson, J.D. AU - MacCoss, M.J. AU - Smith, R.D. AU - Baker, E.S. T2 - Journal of the American Society for Mass Spectrometry AB - Recent advances in ion mobility spectrometry (IMS) have illustrated its power in determining the structural characteristics of a molecule, especially when coupled with other separations dimensions such as liquid chromatography (LC) and mass spectrometry (MS). However, these three separation techniques together greatly complicate data analyses, making better informatics tools essential for assessing the resulting data. In this manuscript, Skyline was adapted to analyze LC-IMS-CID-MS data from numerous instrument vendor datasets and determine the effect of adding the IMS dimension into the normal LC-MS molecular pipeline. For the initial evaluation, a tryptic digest of bovine serum albumin (BSA) was spiked into a yeast protein digest at seven different concentrations, and Skyline was able to rapidly analyze the MS and CID-MS data for 38 of the BSA peptides. Calibration curves for the precursor and fragment ions were assessed with and without the IMS dimension. In all cases, addition of the IMS dimension removed noise from co-eluting peptides with close m/z values, resulting in calibration curves with greater linearity and lower detection limits. This study presents an important informatics development since to date LC-IMS-CID-MS data from the different instrument vendors is often assessed manually and cannot be analyzed quickly. Because these evaluations require days for the analysis of only a few target molecules in a limited number of samples, it is unfeasible to evaluate hundreds of targets in numerous samples. Thus, this study showcases Skyline's ability to work with the multidimensional LC-IMS-CID-MS data and provide biological and environmental insights rapidly. Graphical Abstract ᅟ. DA - 2018/// PY - 2018/// DO - 10.1007/s13361-018-2028-5 VL - 29 IS - 11 SP - 2182-2188 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85054891413&partnerID=MN8TOARS KW - Ion mobility spectrometry KW - Skyline KW - Data independent acquisition KW - Proteomics ER - TY - JOUR TI - Towards Discovery and Targeted Peptide Biomarker Detection Using nanoESI-TIMS-TOF MS AU - Garabedian, A. AU - Benigni, P. AU - Ramirez, C.E. AU - Baker, E.S. AU - Liu, T. AU - Smith, R.D. AU - Fernandez-Lima, F. T2 - Journal of the American Society for Mass Spectrometry AB - In the present work, the potential of trapped ion mobility spectrometry coupled to TOF mass spectrometry (TIMS-TOF MS) for discovery and targeted monitoring of peptide biomarkers from human-in-mouse xenograft tumor tissue was evaluated. In particular, a TIMS-MS workflow was developed for the detection and quantification of peptide biomarkers using internal heavy analogs, taking advantage of the high mobility resolution (R = 150-250) prior to mass analysis. Five peptide biomarkers were separated, identified, and quantified using offline nanoESI-TIMS-CID-TOF MS; the results were in good agreement with measurements using a traditional LC-ESI-MS/MS proteomics workflow. The TIMS-TOF MS analysis permitted peptide biomarker detection based on accurate mobility, mass measurements, and high sequence coverage for concentrations in the 10-200 nM range, while simultaneously achieving discovery measurements of not initially targeted peptides as markers from the same proteins and, eventually, other proteins. Graphical Abstract ᅟ. DA - 2018/// PY - 2018/// DO - 10.1007/s13361-017-1787-8 VL - 29 IS - 5 SP - 817-826 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85042265514&partnerID=MN8TOARS KW - Discovery and targeted monitoring KW - Trapped ion mobility spectrometry KW - Mass KW - Spectrometry KW - Biomarker detection KW - Quantitative proteomics ER - TY - JOUR TI - Improved Sensitivity and Separations for Phosphopeptides using Online Liquid Chromotography Coupled with Structures for Lossless Ion Manipulations Ion Mobility-Mass Spectrometry AU - Chouinard, C.D. AU - Nagy, G. AU - Webb, I.K. AU - Shi, T. AU - Baker, E.S. AU - Prost, S.A. AU - Liu, T. AU - Ibrahim, Y.M. AU - Smith, R.D. T2 - Analytical Chemistry AB - Phosphoproteomics greatly augments proteomics and holds tremendous potential for insights into the modulation of biological systems for various disease states. However, numerous challenges hinder conventional methods in terms of measurement sensitivity, throughput, quantification, and capabilities for confident phosphopeptide and phosphosite identification. In this work, we report the first example of integrating structures for lossless ion manipulations ion mobility–mass spectrometry (SLIM IM–MS) with online reversed-phase liquid chromatography (LC) to evaluate its potential for addressing the aforementioned challenges. A mixture of 51 heavy-labeled phosphopeptides was analyzed with a SLIM IM module having integrated ion accumulation and long-path separation regions. The SLIM IM–MS provided limits of detection as low as 50–100 pM (50–100 amol/μL) for several phosphopeptides, with the potential for significant further improvements. In addition, conventionally problematic phosphopeptide isomers could be resolved following an 18 m SLIM IM separation. The 2-D LC–IM peak capacity was estimated as ∼9000 for a 90 min LC separation coupled to an 18 m SLIM IM separation, considerably higher than LC alone and providing a basis for both improved identification and quantification, with additional gains projected with the future use of longer path SLIM IM separations. Thus, LC–SLIM IM–MS offers great potential for improving the sensitivity, separation, and throughput of phosphoproteomics analyses. DA - 2018/// PY - 2018/// DO - 10.1021/acs.analchem.8b02397 VL - 90 IS - 18 SP - 10889-10896 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85052897753&partnerID=MN8TOARS ER - TY - JOUR TI - Evaluating lipid mediator structural complexity using ion mobility spectrometry combined with mass spectrometry AU - Kyle, J.E. AU - Aly, N. AU - Zheng, X. AU - Burnum-Johnson, K.E. AU - Smith, R.D. AU - Baker, E.S. T2 - Bioanalysis AB - Lipid mediators (LMs) are broadly defined as a class of bioactive lipophilic molecules that regulate cell-to-cell communication events with many having a strong correlation with various human diseases and conditions. LMs are usually analyzed with LC-MS, but their numerous isomers greatly complicate the measurements with essentially identical fragmentation spectra and LC separations are not always sufficient for distinguishing the features. Results/methodology: In this work, we characterized LMs using ion mobility spectrometry (IMS) coupled with MS (IMS-MS). The collision cross-sections and m/z values from the IMS and MS analyses displayed distinct trend lines. Specifically, the structural trend lines for sodiated LMs originating from docosahexaenoic acid had the smallest collision cross-section values in relation to m/z, while those from linoleic acid had the largest. LC-IMS-MS analyses were also performed on LMs in flu infected mouse tissue samples. These multidimensional studies were able to assess known LMs while also detecting new species.Adding IMS separations to conventional LC-MS analyses show great utility for enabling better identification and characterization of LMs in complex biological samples. DA - 2018/// PY - 2018/// DO - 10.4155/bio-2017-0245 VL - 10 IS - 5 SP - 279-289 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85043975901&partnerID=MN8TOARS KW - collision cross-section KW - ion mobility spectrometry KW - lipid mediators ER - TY - JOUR TI - Editorial overview: Omics AU - Barran, P. AU - Baker, E. T2 - Current Opinion in Chemical Biology DA - 2018/// PY - 2018/// DO - 10.1016/j.cbpa.2018.02.007 VL - 42 SP - A1-A2 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85042395623&partnerID=MN8TOARS ER - TY - JOUR TI - An algorithm to correct saturated mass spectrometry ion abundances for enhanced quantitation and mass accuracy in omic studies AU - Bilbao, A. AU - Gibbons, B.C. AU - Slysz, G.W. AU - Crowell, K.L. AU - Monroe, M.E. AU - Ibrahim, Y.M. AU - Smith, R.D. AU - Payne, S.H. AU - Baker, E.S. T2 - International Journal of Mass Spectrometry AB - The mass accuracy and peak intensity of ions detected by mass spectrometry (MS) measurements are essential to facilitate compound identification and quantitation. However, high concentration species can yield erroneous results if their ion intensities reach beyond the limits of the detection system, leading to distorted and non-ideal detector response (e.g. saturation), and largely precluding the calculation of accurate m/z and intensity values. Here we present an open source computational method to correct peaks above a defined intensity (saturated) threshold determined by the MS instrumentation such as the analog-to-digital converters or time-to-digital converters used in conjunction with time-of-flight MS. In this method, the isotopic envelope for each observed ion above the saturation threshold is compared to its expected theoretical isotopic distribution. The most intense isotopic peak for which saturation does not occur is then utilized to re-calculate the precursor m/z and correct the intensity, resulting in both higher mass accuracy and greater dynamic range. The benefits of this approach were evaluated with proteomic and lipidomic datasets of varying complexities. After correcting the high concentration species, reduced mass errors and enhanced dynamic range were observed for both simple and complex omic samples. Specifically, the mass error dropped by more than 50% in most cases for highly saturated species and dynamic range increased by 1-2 orders of magnitude for peptides in a blood serum sample. DA - 2018/// PY - 2018/// DO - 10.1016/j.ijms.2017.11.003 VL - 427 SP - 91-99 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85034616829&partnerID=MN8TOARS KW - Mass spectrometry KW - Detector saturation KW - Analog-to-digital converter saturation KW - Saturation correction KW - Isotopic envelope KW - Isotopic ratios KW - Quantitation ER - TY - JOUR TI - A Customizable Flow Injection System for Automated, High Throughput, and Time Sensitive Ion Mobility Spectrometry and Mass Spectrometry Measurements AU - Orton, D.J. AU - Tfaily, M.M. AU - Moore, R.J. AU - Lamarche, B.L. AU - Zheng, X. AU - Fillmore, T.L. AU - Chu, R.K. AU - Weitz, K.K. AU - Monroe, M.E. AU - Kelly, R.T. AU - Smith, R.D. AU - Baker, E.S. T2 - Analytical Chemistry AB - To better understand disease conditions and environmental perturbations, multiomic studies combining proteomic, lipidomic, and metabolomic analyses are vastly increasing in popularity. In a multiomic study, a single sample is typically extracted in multiple ways, and various analyses are performed using different instruments, most often based upon mass spectrometry (MS). Thus, one sample becomes many measurements, making high throughput and reproducible evaluations a necessity. One way to address the numerous samples and varying instrumental conditions is to utilize a flow injection analysis (FIA) system for rapid sample injections. While some FIA systems have been created to address these challenges, many have limitations such as costly consumables, low pressure capabilities, limited pressure monitoring, and fixed flow rates. To address these limitations, we created an automated, customizable FIA system capable of operating at a range of flow rates (∼50 nL/min to 500 μL/min) to accommodate both low- and high-flow MS ionization sources. This system also functions at varying analytical throughputs from 24 to 1200 samples per day to enable different MS analysis approaches. Applications ranging from native protein analyses to molecular library construction were performed using the FIA system, and results showed a highly robust and reproducible platform capable of providing consistent performance over many days without carryover, as long as washing buffers specific to each molecular analysis were utilized. DA - 2018/// PY - 2018/// DO - 10.1021/acs.analchem.7b02986 VL - 90 IS - 1 SP - 737-744 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85040192500&partnerID=MN8TOARS ER - TY - JOUR TI - Guest editor's personal foreward AU - Baker, E.S. AU - Ogorzalek Loo, R. T2 - International Journal of Mass Spectrometry DA - 2018/// PY - 2018/// DO - 10.1016/j.ijms.2018.03.002 VL - 427 SP - 1-3 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85044001941&partnerID=MN8TOARS ER - TY - JOUR TI - Distinguishing enantiomeric amino acids with chiral cyclodextrin adducts and structures for lossless ion manipulations AU - Nagy, G. AU - Chouinard, C.D. AU - Attah, I.K. AU - Webb, I.K. AU - Garimella, S.V.B. AU - Ibrahim, Y.M. AU - Baker, E.S. AU - Smith, R.D. T2 - Electrophoresis AB - Abstract Enantiomeric molecular evaluations remain an enormous challenge for current analytical techniques. To date, derivatization strategies and long separation times are generally required in these studies, and the development and implementation of new approaches are needed to increase speed and distinguish currently unresolvable compounds. Herein, we describe a method using chiral cyclodextrin adducts and structures for lossless ion manipulations (SLIM) and serpentine ultralong path with extended routing (SUPER) ion mobility (IM) to achieve rapid, high resolution separations of d and l enantiomeric amino acids. In the analyses, a chiral cyclodextrin is added to each sample. Two cyclodextrins were found to complex each amino acid molecule (i.e. potentially sandwiching the amino acid in their cavities) and forming host‐guest noncovalent complexes that were distinct for each d and l amino acid pair studied and thus separable with IM in SLIM devices. The SLIM was also used to accumulate much larger ion populations than previously feasible for evaluation and therefore allow enantiomeric measurements of higher sensitivity, with gains in resolution from our ultralong path separation capabilities, than previously reported by any other IM–based approach. DA - 2018/// PY - 2018/// DO - 10.1002/elps.201800294 VL - 39 IS - 24 SP - 3148-3155 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85053448912&partnerID=MN8TOARS KW - Chiral separations KW - Cyclodextrins KW - Enantiomers KW - Ion mobility-mass spectrometry KW - Structures for lossless ion manipulations ER - TY - JOUR TI - Comparing residential contamination in a Houston environmental justice neighborhood before and after Hurricane Harvey AU - Horney, J.A. AU - Casillas, G.A. AU - Baker, E. AU - Stone, K.W. AU - Kirsch, K.R. AU - Camargo, K. AU - Wade, T.L. AU - McDonald, T.J. T2 - PLoS ONE AB - Introduction Polycyclic aromatic hydrocarbons (PAHs) are complex environmental toxicants. Exposure to them has been linked to adverse health outcomes including cancer, as well as diseases of the skin, liver, and immune system. Based on an ongoing community engagement partnership with stakeholder groups and residents, we conducted a small longitudinal study to assess domestic exposure to PAHs among residents of Manchester, an environmental justice neighborhood located in the East End of Houston, TX. Methods In December, 2016, we used fiber wipes to collect samples of household dust from 25 homes in Manchester. Following Hurricane Harvey, in September 2017, we revisited 24 of the 25 homes to collect soil samples from the front yards of the same homes. Wipes and soil were analyzed for the presence of PAHs using gas chromatography–mass spectrometry (GC-MS) methods. Principal component analysis plots, heatmaps, and PAH ratios were used to compare pre- and post-Hurricane Harvey samples. Results While direct comparison is not possible, we present three methods for comparing PAHs found in pre-hurricane fiber wipes and post-hurricane soil samples. The methods demonstrate that the PAHs found before and after Hurricane Harvey are likely from similar sources and that those sources are most likely to be associated with combustion. We also found evidence of redistribution of PAHs due to extreme flooding associated with Hurricane Harvey. Discussion Residents of the Manchester neighborhood of Houston, TX, are exposed to a range of PAHs in household dust and outdoor soil. While it was not possible to compare directly, we were able to use several methods to assess detected concentrations, changes in site-specific PAH allocations, and PAH origination. Additional research is needed to identify specific sources of domestic PAH exposure in these communities and continued work involving community members and policy makers should aim to develop interventions to reduce domestic exposure to and prevent negative health outcomes from PAHs. DA - 2018/// PY - 2018/// DO - 10.1371/journal.pone.0192660 VL - 13 IS - 2 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85041735845&partnerID=MN8TOARS ER - TY - JOUR TI - Cell type-resolved human lung lipidome reveals cellular cooperation in lung function AU - Kyle, J.E. AU - Clair, G. AU - Bandyopadhyay, G. AU - Misra, R.S. AU - Zink, E.M. AU - Bloodsworth, K.J. AU - Shukla, A.K. AU - Du, Y. AU - Lillis, J. AU - Myers, J.R. AU - Ashton, J. AU - Bushnell, T. AU - Cochran, M. AU - Deutsch, G. AU - Baker, E.S. AU - Carson, J.P. AU - Mariani, T.J. AU - Xu, Y. AU - Whitsett, J.A. AU - Pryhuber, G. AU - Ansong, C. T2 - Scientific Reports AB - Abstract Cell type-resolved proteome analyses of the brain, heart and liver have been reported, however a similar effort on the lipidome is currently lacking. Here we applied liquid chromatography-tandem mass spectrometry to characterize the lipidome of major lung cell types isolated from human donors, representing the first lipidome map of any organ. We coupled this with cell type-resolved proteomics of the same samples (available at Lungmap.net). Complementary proteomics analyses substantiated the functional identity of the isolated cells. Lipidomics analyses showed significant variations in the lipidome across major human lung cell types, with differences most evident at the subclass and intra-subclass (i.e. total carbon length of the fatty acid chains) level. Further, lipidomic signatures revealed an overarching posture of high cellular cooperation within the human lung to support critical functions. Our complementary cell type-resolved lipid and protein datasets serve as a rich resource for analyses of human lung function. DA - 2018/// PY - 2018/// DO - 10.1038/s41598-018-31640-x VL - 8 IS - 1 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85053010617&partnerID=MN8TOARS ER - TY - JOUR TI - Application of multiplexed ion mobility spectrometry towards the identification of host protein signatures of treatment effect in pulmonary tuberculosis AU - Kedia, K. AU - Wendler, J.P. AU - Baker, E.S. AU - Burnum-Johnson, K.E. AU - Jarsberg, L.G. AU - Stratton, K.G. AU - Wright, A.T. AU - Piehowski, P.D. AU - Gritsenko, M.A. AU - Lewinsohn, D.M. AU - Sigal, G.B. AU - Weiner, M.H. AU - Smith, R.D. AU - Jacobs, J.M. AU - Nahid, P. T2 - Tuberculosis AB - The monitoring of TB treatments in clinical practice and clinical trials relies on traditional sputum-based culture status indicators at specific time points. Accurate, predictive, blood-based protein markers would provide a simpler and more informative view of patient health and response to treatment. We utilized sensitive, high throughput multiplexed ion mobility-mass spectrometry (IM-MS) to characterize the serum proteome of TB patients at the start of and at 8 weeks of rifamycin-based treatment. We sought to identify treatment specific signatures within patients as well as correlate the proteome signatures to various clinical markers of treatment efficacy. Serum samples were collected from 289 subjects enrolled in CDC TB Trials Consortium Study 29 at time of enrollment and at the end of the intensive phase (after 40 doses of TB treatment). Serum proteins were immunoaffinity-depleted of high abundant components, digested to peptides and analyzed for data acquisition utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS). Linear mixed models were utilized to identify serum protein changes in the host response to antibiotic treatment as well as correlations with culture status end points. A total of 10,137 peptides corresponding to 872 proteins were identified, quantified, and used for statistical analysis across the longitudinal patient cohort. In response to TB treatment, 244 proteins were significantly altered. Pathway/network comparisons helped visualize the interconnected proteins, identifying up regulated (lipid transport, coagulation cascade, endopeptidase activity) and down regulated (acute phase) processes and pathways in addition to other cross regulated networks (inflammation, cell adhesion, extracellular matrix). Detection of possible lung injury serum proteins such as HPSE, significantly downregulated upon treatment. Analyses of microbiologic data over time identified a core set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2) which change in response to treatment and also strongly correlate with culture status. A similar set of proteins at baseline were found to be predictive of week 6 and 8 culture status. A comprehensive host serum protein dataset reflective of TB treatment effect is defined. A repeating set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2, among others) were found to change significantly in response to treatment, to strongly correlate with culture status, and at baseline to be predictive of future culture conversion. If validated in cohorts with long term follow-up to capture failure and relapse of TB, these protein markers could be developed for monitoring of treatment in clinical trials and in patient care. DA - 2018/// PY - 2018/// DO - 10.1016/j.tube.2018.07.005 VL - 112 SP - 52-61 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85050666053&partnerID=MN8TOARS KW - Ion mobility spectrometry KW - Proteomics KW - Tuberculosis KW - Antibiotic treatment ER - TY - JOUR TI - Heavy Metal Exposure and Metabolic Syndrome: Evidence from Human and Model System Studies AU - Planchart, Antonio AU - Green, Adrian AU - Hoyo, Cathrine AU - Mattingly, Carolyn J. T2 - Current Environmental Health Reports AB - Metabolic syndrome (MS) describes the co-occurrence of conditions that increase one’s risk for heart disease and other disorders such as diabetes and stroke. The worldwide increase in the prevalence of MS cannot be fully explained by lifestyle factors such as sedentary behavior and caloric intake alone. Environmental exposures, such as heavy metals, have been implicated, but results are conflicting and possible mechanisms remain unclear. To assess recent progress in determining a possible role between heavy metal exposure and MS, we reviewed epidemiological and model system data for cadmium (Cd), lead (Pb), and mercury (Hg) from the last decade. Data from 36 epidemiological studies involving 17 unique countries/regions and 13 studies leveraging model systems are included in this review. Epidemiological and model system studies support a possible association between heavy metal exposure and MS or comorbid conditions; however, results remain conflicting. Epidemiological studies were predominantly cross-sectional and collectively, they highlight a global interest in this question and reveal evidence of differential susceptibility by sex and age to heavy metal exposures. In vivo studies in rats and mice and in vitro cell-based assays provide insights into potential mechanisms of action relevant to MS including altered regulation of lipid and glucose homeostasis, adipogenesis, and oxidative stress. Heavy metal exposure may contribute to MS or comorbid conditions; however, available data are conflicting. Causal inference remains challenging as epidemiological data are largely cross-sectional; and variation in study design, including samples used for heavy metal measurements, age of subjects at which MS outcomes are measured; the scope and treatment of confounding factors; and the population demographics vary widely. Prospective studies, standardization or increased consistency across study designs and reporting, and consideration of molecular mechanisms informed by model system studies are needed to better assess potential causal links between heavy metal exposure and MS. DA - 2018/2/19/ PY - 2018/2/19/ DO - 10.1007/s40572-018-0182-3 VL - 5 IS - 1 SP - 110-124 J2 - Curr Envir Health Rpt LA - en OP - SN - 2196-5412 UR - http://dx.doi.org/10.1007/s40572-018-0182-3 DB - Crossref KW - Metabolic syndrome KW - Diabetes KW - Heavy metals KW - Cadmium KW - Pb KW - Mercury ER - TY - JOUR TI - Cadmium exposure increases the risk of juvenile obesity: a human and zebrafish comparative study AU - Green, Adrian J. AU - Hoyo, Cathrine AU - Mattingly, Carolyn J. AU - Luo, Yiwen AU - Tzeng, Jung-Ying AU - Murphy, Susan K. AU - Buchwalter, David B. AU - Planchart, Antonio T2 - International Journal of Obesity AB - Human obesity is a complex metabolic disorder disproportionately affecting people of lower socioeconomic strata, and ethnic minorities, especially African Americans and Hispanics. Although genetic predisposition and a positive energy balance are implicated in obesity, these factors alone do not account for the excess prevalence of obesity in lower socioeconomic populations. Therefore, environmental factors, including exposure to pesticides, heavy metals, and other contaminants, are agents widely suspected to have obesogenic activity, and they also are spatially correlated with lower socioeconomic status. Our study investigates the causal relationship between exposure to the heavy metal, cadmium (Cd), and obesity in a cohort of children and in a zebrafish model of adipogenesis.An extensive collection of first trimester maternal blood samples obtained as part of the Newborn Epigenetics Study (NEST) was analyzed for the presence of Cd, and these results were cross analyzed with the weight-gain trajectory of the children through age 5 years. Next, the role of Cd as a potential obesogen was analyzed in an in vivo zebrafish model.Our analysis indicates that the presence of Cd in maternal blood during pregnancy is associated with increased risk of juvenile obesity in the offspring, independent of other variables, including lead (Pb) and smoking status. Our results are recapitulated in a zebrafish model, in which exposure to Cd at levels approximating those observed in the NEST study is associated with increased adiposity.Our findings identify Cd as a potential human obesogen. Moreover, these observations are recapitulated in a zebrafish model, suggesting that the underlying mechanisms may be evolutionarily conserved, and that zebrafish may be a valuable model for uncovering pathways leading to Cd-mediated obesity in human populations. DA - 2018/2/20/ PY - 2018/2/20/ DO - 10.1038/S41366-018-0036-Y VL - 42 IS - 7 SP - 1285-1295 J2 - Int J Obes LA - en OP - SN - 0307-0565 1476-5497 UR - http://dx.doi.org/10.1038/S41366-018-0036-Y DB - Crossref ER - TY - JOUR TI - Elucidating Gene-by-Environment Interactions Associated with Differential Susceptibility to Chemical Exposure. AU - Balik-Meisner, M AU - Truong, L AU - Scholl, EH AU - La, Du JK AU - Tanguay, RL AU - Reif, DM T2 - Environmental health perspectives AB - Background: Modern societies are exposed to vast numbers of potentially hazardous chemicals. Despite demonstrated linkages between chemical exposure and severe health effects, there are limited, often conflicting, data on how adverse health effects of exposure differ across individuals. Objectives: We tested the hypothesis that population variability in response to certain chemicals could elucidate a role for gene–environment interactions (GxE) in differential susceptibility. Methods: High-throughput screening (HTS) data on thousands of chemicals in genetically heterogeneous zebrafish were leveraged to identify a candidate chemical (Abamectin) with response patterns indicative of population susceptibility differences. We tested the prediction by generating genome-wide sequence data for 276 individual zebrafish displaying susceptible (Affected) vs. resistant (Unaffected) phenotypes following identical chemical exposure. Results: We found GxE associated with differential susceptibility in the sox7 promoter region and then confirmed gene expression differences between phenotypic response classes. Conclusions: The results for Abamectin in zebrafish demonstrate that GxE associated with naturally occurring, population genetic variation play a significant role in mediating individual response to chemical exposure. https://doi.org/10.1289/EHP2662 DA - 2018/6// PY - 2018/6// DO - 10.1289/ehp2662 VL - 6 IS - 6 UR - http://europepmc.org/abstract/med/29968567 ER - TY - JOUR TI - Ligand-mediated protein degradation reveals functional conservation among sequence variants of the CUL4-type E3 ligase substrate receptor cereblon AU - Akuffo, Afua A. AU - Alontaga, Aileen Y. AU - Metcalf, Rainer AU - Beatty, Matthew S. AU - Becker, Andreas AU - McDaniel, Jessica M. AU - Hesterberg, Rebecca S. AU - Goodheart, William E. AU - Gunawan, Steven AU - Ayaz, Muhammad AU - Yang, Yan AU - Karim, Md Rezaul AU - Orobello, Morgan E. AU - Daniel, Kenyon AU - Guida, Wayne AU - Yoder, Jeffrey A. AU - Rajadhyaksha, Anjali M. AU - Schönbrunn, Ernst AU - Lawrence, Harshani R. AU - Lawrence, Nicholas J. AU - Epling-Burnette, Pearlie K. T2 - Journal of Biological Chemistry AB - Upon binding to thalidomide and other immunomodulatory drugs, the E3 ligase substrate receptor cereblon (CRBN) promotes proteosomal destruction by engaging the DDB1–CUL4A–Roc1–RBX1 E3 ubiquitin ligase in human cells but not in mouse cells, suggesting that sequence variations in CRBN may cause its inactivation. Therapeutically, CRBN engagers have the potential for broad applications in cancer and immune therapy by specifically reducing protein expression through targeted ubiquitin-mediated degradation. To examine the effects of defined sequence changes on CRBN’s activity, we performed a comprehensive study using complementary theoretical, biophysical, and biological assays aimed at understanding CRBN’s nonprimate sequence variations. With a series of recombinant thalidomide-binding domain (TBD) proteins, we show that CRBN sequence variants retain their drug-binding properties to both classical immunomodulatory drugs and dBET1, a chemical compound and targeting ligand designed to degrade bromodomain-containing 4 (BRD4) via a CRBN-dependent mechanism. We further show that dBET1 stimulates CRBN’s E3 ubiquitin–conjugating function and degrades BRD4 in both mouse and human cells. This insight paves the way for studies of CRBN-dependent proteasome-targeting molecules in nonprimate models and provides a new understanding of CRBN’s substrate-recruiting function. Upon binding to thalidomide and other immunomodulatory drugs, the E3 ligase substrate receptor cereblon (CRBN) promotes proteosomal destruction by engaging the DDB1–CUL4A–Roc1–RBX1 E3 ubiquitin ligase in human cells but not in mouse cells, suggesting that sequence variations in CRBN may cause its inactivation. Therapeutically, CRBN engagers have the potential for broad applications in cancer and immune therapy by specifically reducing protein expression through targeted ubiquitin-mediated degradation. To examine the effects of defined sequence changes on CRBN’s activity, we performed a comprehensive study using complementary theoretical, biophysical, and biological assays aimed at understanding CRBN’s nonprimate sequence variations. With a series of recombinant thalidomide-binding domain (TBD) proteins, we show that CRBN sequence variants retain their drug-binding properties to both classical immunomodulatory drugs and dBET1, a chemical compound and targeting ligand designed to degrade bromodomain-containing 4 (BRD4) via a CRBN-dependent mechanism. We further show that dBET1 stimulates CRBN’s E3 ubiquitin–conjugating function and degrades BRD4 in both mouse and human cells. This insight paves the way for studies of CRBN-dependent proteasome-targeting molecules in nonprimate models and provides a new understanding of CRBN’s substrate-recruiting function. DA - 2018/2/15/ PY - 2018/2/15/ DO - 10.1074/jbc.m117.816868 VL - 293 IS - 16 SP - 6187-6200 J2 - J. Biol. Chem. LA - en OP - SN - 0021-9258 1083-351X UR - http://dx.doi.org/10.1074/jbc.M117.816868 DB - Crossref ER - TY - JOUR TI - Carbon dynamics of paper, engineered wood products and bamboo in landfills: evidence from reactor studies AU - Ximenes, Fabiano A. AU - Kathuria, Amrit AU - Barlaz, Morton A. AU - Cowie, Annette L. T2 - CARBON BALANCE AND MANAGEMENT AB - There has been growing interest in the development of waste-specific decay factors for estimation of greenhouse gas emissions from landfills in national greenhouse gas inventories. Although engineered wood products (EWPs) and paper represent a substantial component of the solid waste stream, there is limited information available on their carbon dynamics in landfills. The objective of this study was to determine the extent of carbon loss for EWPs and paper products commonly used in Australia. Experiments were conducted under laboratory conditions designed to simulate optimal anaerobic biodegradation in a landfill.Methane generation rates over incubations of 307-677 days ranged from zero for medium-density fibreboard (MDF) to 326 mL CH4 g-1 for copy paper. Carbon losses for particleboard and MDF ranged from 0.7 to 1.6%, consistent with previous estimates. Carbon loss for the exterior wall panel product (2.8%) was consistent with the expected value for blackbutt, the main wood type used in its manufacture. Carbon loss for bamboo (11.4%) was significantly higher than for EWPs. Carbon losses for the three types of copy paper tested ranged from 72.4 to 82.5%, and were significantly higher than for cardboard (27.3-43.8%). Cardboard that had been buried in landfill for 20 years had a carbon loss of 27.3%-indicating that environmental conditions in the landfill did not support complete decomposition of the available carbon. Thus carbon losses for paper products as measured in bioreactors clearly overestimate those in actual landfills. Carbon losses, as estimated by gas generation, were on average lower than those derived by mass balance. The low carbon loss for particleboard and MDF is consistent with carbon loss for Australian wood types described in previous studies. A factor for carbon loss for combined EWPs and wood in landfills in Australia of 1.3% and for paper of 48% is proposed.The new suggested combined decay factor for wood and EWPs represents a significant reduction from the current factor used in the Australian greenhouse gas inventory; whereas the suggested decay factor for paper is similar to the current decay factor. Our results improve current understanding of the carbon dynamics of harvested wood products, and allow more refined estimates of methane emissions from landfills. DA - 2018/12/27/ PY - 2018/12/27/ DO - 10.1186/s13021-018-0115-3 VL - 13 SP - SN - 1750-0680 KW - Carbon KW - Engineered wood products KW - Paper KW - Decay KW - Methane KW - Landfill KW - Greenhouse gas inventory ER - TY - JOUR TI - Chemistry-Wide Association Studies (CWAS): A Novel Framework for Identifying and Interpreting Structure-Activity Relationships AU - Low, Yen S. AU - Alves, Vinicius M. AU - Fourches, Denis AU - Sedykh, Alexander AU - Andrade, Carolina Horta AU - Muratov, Eugene N. AU - Rusyn, Ivan AU - Tropsha, Alexander T2 - JOURNAL OF CHEMICAL INFORMATION AND MODELING AB - Quantitative structure–activity relationships (QSAR) models are often seen as a “black box” because they are considered difficult to interpret. Meanwhile, qualitative approaches, e.g., structural alerts (SA) or read-across, provide mechanistic insight, which is preferred for regulatory purposes, but predictive accuracy of such approaches is often low. Herein, we introduce the chemistry-wide association study (CWAS) approach, a novel framework that both addresses such deficiencies and combines advantages of statistical QSAR and alert-based approaches. The CWAS framework consists of the following steps: (i) QSAR model building for an end point of interest, (ii) identification of key chemical features, (iii) determination of communities of such features disproportionately co-occurring more frequently in the active than in the inactive class, and (iv) assembling these communities to form larger (and not necessarily chemically connected) novel structural alerts with high specificity. As a proof-of-concept, we have applied CWAS to model Ames mutagenicity and Stevens–Johnson Syndrome (SJS). For the well-studied Ames mutagenicity data set, we identified 76 important individual fragments and assembled co-occurring fragments into SA both replicative of known as well as representing novel mutagenicity alerts. For the SJS data set, we identified 29 important fragments and assembled co-occurring communities into SA including both known and novel alerts. In summary, we demonstrate that CWAS provides a new framework to interpret predictive QSAR models and derive refined structural alerts for more effective design and safety assessment of drugs and drug candidates. DA - 2018/11// PY - 2018/11// DO - 10.1021/acs.jcim.8b00450 VL - 58 IS - 11 SP - 2203-2213 SN - 1549-960X ER - TY - JOUR TI - The Good, the Bad, and the Lethal: Gene Expression and Metabolomics Reveal Physiological Mechanisms Underlying Chronic Thermal Effects in Mayfly Larvae (Neocloeon triangulifer) AU - Chou, Hsuan AU - Pathmasiri, Wimal AU - Deese-spruill, Jocelin AU - Sumner, Susan J. AU - Jima, Dereje D. AU - Funk, David H. AU - Jackson, John K. AU - Sweeney, Bernard W. AU - Buchwalter, David B. T2 - FRONTIERS IN ECOLOGY AND EVOLUTION AB - Temperature dictates the performance of aquatic ectotherms. However, the physiological and biochemical processes that drive thermally-mediated life history patterns (and limits) remain poorly understood because they are rarely studied simultaneously. In our previous work, we have established life history outcomes (e.g. survivorship, development time, growth rates and fitness) in mayflies (Neocloeon triangulifer) reared at static temperatures ranging from 14°C - 30°C at 2°C intervals. In this study, we conducted biochemical measurements (RT-qPCR of select genes and targeted, quantitative metabolomic profiling) on N. triangulifer mature larvae reared at temperatures associated with excellent survival and fitness (22-24°C), compromised survival and fitness (28°C), and chronic lethality (30°C -larvae survived for a few weeks but failed to emerge to adulthood). Patterns of gene expression were similar to those observed in acute ramping experiments reported previously: larvae reared at 30°C resulted in significant upregulation in the thermally responsive gene HEAT SHOCK PROTEIN 90 (HSP90) but no significant changes in hypoxia responsive genes (EGG LAYING DEFECTIVE 9 (EGL-9) and LACTATE DEHYDROGENASE (LDH)). Additionally, primers for genes associated with energy: INSULIN RECEPTOR (IR), mechanistic TARGET OF RAPAMYCIN (mTOR) and TREHALOSE 6 PHOSPHATE SYNTHASE (T6PS) were developed for this study. IR and mTOR were significantly upregulated while T6PS showed trend of downregulation in larvae reared at 30°C. Metabolomic profiles revealed general depletion of lipids and acylcarnitines in larvae exposed to chronic thermal stress, suggesting that larvae were energetically challenged despite continuous access to food. For example, concentrations of lysoPhosphatidylcholine (lysoPC) a C20:3 decreased as fitness decreased with increasing temperature (2.3 fold and 2.4 fold at 28 and 30°C relative to controls). Tissue concentrations of the biogenic amine histamine increased 2.1 and 3.1 fold with increasing temperature, and were strongly and negatively correlated with performance. Thus, both histamine and lysoPC a C20:3 are potential biomarkers of thermal stress. Taken together, our results primarily associate energetic challenge with thermally mediated fitness reduction in N. triangulifer. DA - 2018/3/23/ PY - 2018/3/23/ DO - 10.3389/fevo.2018.00027 VL - 6 SP - SN - 2296-701X KW - aquatic insects KW - mayfly KW - thermal limits KW - metabolomics KW - temperature ER - TY - JOUR TI - Evaluation of Digital Image Recognition Methods for Mass Spectrometry Imaging Data Analysis AU - Ekelof, Mans AU - Garrard, Kenneth P. AU - Judd, Rika AU - Rosen, Elias P. AU - Xie, De-Yu AU - Kashuba, Angela D. M. AU - Muddiman, David C. T2 - JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY AB - Analyzing mass spectrometry imaging data can be laborious and time consuming, and as the size and complexity of datasets grow, so does the need for robust automated processing methods. We here present a method for comprehensive, semi-targeted discovery of molecular distributions of interest from mass spectrometry imaging data, using widely available image similarity scoring algorithms to rank images by spatial correlation. A fast and powerful batch search method using a MATLAB implementation of structural similarity (SSIM) index scoring with a pre-selected reference distribution is demonstrated for two sample imaging datasets, a plant metabolite study using Artemisia annua leaf, and a drug distribution study using maraviroc-dosed macaque tissue. Graphical Abstract ᅟ. DA - 2018/12// PY - 2018/12// DO - 10.1007/s13361-018-2073-0 VL - 29 IS - 12 SP - 2467-2470 SN - 1879-1123 KW - Mass spectrometry imaging KW - Image recognition KW - SSIM ER - TY - JOUR TI - Neonatal mice exposed to a high-fat diet in utero influence the behaviour of their nursing dam AU - Baptissart, M. AU - Lamb, H.E. AU - To, K. AU - Bradish, C. AU - Tehrani, J. AU - Reif, David AU - Cowley, M. T2 - Proceedings of the Royal Society B: Biological Sciences AB - The behaviour of a nursing dam influences the development, physiology, and behaviour of her offspring. Maternal behaviours can be modulated both by environmental factors, including diet, and by physical or behavioural characteristics of the offspring. In most studies of the effects of the environment on maternal behaviour, F 0 dams nurse their own F 1 offspring. Because the F 1 are indirectly exposed to the environmental stressor in utero in these studies, it is not possible to differentiate between effects on maternal behaviour from direct exposure of the dam and those mediated by changes in the F 1 as a consequence of in utero exposure. In this study, we used a mouse model of high-fat (HF) diet feeding, which has been shown to influence maternal behaviours, combined with cross-fostering to discriminate between these effects. We tested whether the diet of the F 0 dam or the exposure experienced by the F 1 pups in utero is the most significant predictor of maternal behaviour. Neither factor significantly influenced pup retrieval behaviours. However, strikingly, F 1 in utero exposure was a significant predictor of maternal behaviour in the 15 min immediately following pup retrieval while F 0 diet had no discernable effect. Our findings suggest that in utero exposure to HF diet programmes physiological changes in the offspring which influence the maternal behaviours of their dam after birth. DA - 2018/// PY - 2018/// DO - 10.1098/rspb.2018.1237 VL - 285 IS - 1891 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85056612433&partnerID=MN8TOARS ER - TY - JOUR TI - Exploring drug space with ChemMaps.com AU - Borrel, Alexandre AU - Kleinstreuer, Nicole C. AU - Fourches, Denis T2 - BIOINFORMATICS AB - Abstract Motivation Easily navigating chemical space has become more important due to the increasing size and diversity of publicly-accessible databases such as DrugBank, ChEMBL or Tox21. To do so, modelers typically rely on complex projection techniques using molecular descriptors computed for all the chemicals to be visualized. However, the multiple cheminformatics steps required to prepare, characterize, compute and explore those molecules, are technical, typically necessitate scripting skills, and thus represent a real obstacle for non-specialists. Results We developed the ChemMaps.com webserver to easily browse, navigate and mine chemical space. The first version of ChemMaps.com features more than 8000 approved, in development, and rejected drugs, as well as over 47 000 environmental chemicals. Availability and implementation The webserver is freely available at http://www.chemmaps.com. DA - 2018/11/1/ PY - 2018/11/1/ DO - 10.1093/bioinformatics/bty412 VL - 34 IS - 21 SP - 3773-3775 SN - 1460-2059 ER - TY - JOUR TI - IR-MALDESI mass spectrometry imaging of underivatized neurotransmitters in brain tissue of rats exposed to tetrabromobisphenol A AU - Bagley, M. Caleb AU - Ekelof, Mans AU - Rock, Kylie AU - Patisaul, Heather AU - Muddiman, David C. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY AB - There is a pressing need to develop tools for assessing possible neurotoxicity, particularly for chemicals where the mode of action is poorly understood. Tetrabromobisphenol A (TBBPA), a highly abundant brominated flame retardant, has lately been targeted for neurotoxicity analysis by concerned public health entities in the EU and USA because it is a suspected thyroid disruptor and neurotoxicant. In this study, infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) coupled to a Q Exactive Plus mass spectrometer was used for the analysis of neurotransmitters in the brains of rats exposed to TBBPA in gestation and lactation through their mothers. Three neurotransmitters of interest were studied in three selected regions of the brain: caudate putamen, substantia nigra (SN), and dorsal raphe. Stable isotope labeled (SIL) standards were used as internal standards and a means to achieve relative quantification. This study serves as a demonstration of a new application of IR-MALDESI, namely that neurotransmitter distributions can be confidently and rapidly imaged without derivatization. DA - 2018/12// PY - 2018/12// DO - 10.1007/s00216-018-1420-0 VL - 410 IS - 30 SP - 7979-7986 SN - 1618-2650 KW - IR-MALDESI KW - Neurotransmitters KW - Mass spectrometry imaging KW - Exposomics KW - Orbitrap ER - TY - JOUR TI - Toward the Rational Design of Sustainable Hair Dyes Using Cheminformatics Approaches: Step 2. Identification of Hair Dye Substance Database Analogs in the Max Weaver Dye Library AU - Williams, Tova N. AU - Driessche, George A. AU - Valery, Alain R. B. AU - Fourches, Denis AU - Freeman, Harold S. T2 - ACS SUSTAINABLE CHEMISTRY & ENGINEERING AB - We report on part 2 of the cheminformatics-assisted development of sustainable hair dyes with enhanced technical and toxicological properties. In this study, an initial similarity search analysis was performed using two reference probes (C.I. Basic Orange 1 and Orange 2) as structural templates for the identification of potential analogs among the Max Weaver Dye Library (MWDL). The analysis revealed an interesting subset of 158 MWDL compounds that were close analogs of the classical aminoazobenzene dyes. A more detailed similarity search analysis of this subset ultimately led to the selection of four dyes for further in silico quantum calculations and experimental dye uptake (color depth on hair) studies. Results from quantum calculations indicated that the ESP surface properties of these dyes were consistent with nonionic interactions between dye and keratin. Among the four dye analogs, 2-amino-6-methyl-5-(phenyldiazenyl)pyrimidin-4-ol and 2-amino-4-chloro-1,6-dimethyl-5-(phenyldiazenyl)-pyrimidin-1-ium methyl sulfate achieved the best dye uptake on hair (∑K/S 227.31 and 149.26). The results of this study show that cheminformatics-based tools can be used to both build and screen dye databases containing potential alternatives to colorants believed to pose environmental concerns, providing a more sustainable (green) approach to hair dye design, by reducing the number of compounds requiring synthesis and analysis before suitable replacements are identified. DA - 2018/11/5/ PY - 2018/11/5/ DO - 10.1021/acssuschemeng.8b02882 VL - 6 IS - 11 SP - 14248-14256 SN - 2168-0485 KW - Cheminformatics KW - Hair dyes KW - Hair Dye Substance Database KW - Max Weaver Dye Library KW - Skin sensitization KW - Sustainability ER - TY - JOUR TI - Cheminformatics-based enumeration and analysis of large libraries of macrolide scaffolds AU - Zin, Phyo Phyo Kyaw AU - Williams, Gavin AU - Fourches, Denis T2 - JOURNAL OF CHEMINFORMATICS AB - We report on the development of a cheminformatics enumeration technology and the analysis of a resulting large dataset of virtual macrolide scaffolds. Although macrolides have been shown to have valuable biological properties, there is no ready-to-screen virtual library of diverse macrolides in the public domain. Conducting molecular modeling (especially virtual screening) of these complex molecules is highly relevant as the organic synthesis of these compounds, when feasible, typically requires many synthetic steps, and thus dramatically slows the discovery of new bioactive macrolides. Herein, we introduce a cheminformatics approach and associated software that allows for designing and generating libraries of virtual macrocycle/macrolide scaffolds with user-defined constitutional and structural constraints (e.g., types and numbers of structural motifs to be included in the macrocycle, ring size, maximum number of compounds generated). To study the chemical diversity of such generated molecules, we enumerated V1M (Virtual 1 million Macrolide scaffolds) library, each containing twelve common structural motifs. For each macrolide scaffold, we calculated several key properties, such as molecular weight, hydrogen bond donors/acceptors, topological polar surface area. In this study, we discuss (1) the initial concept and current features of our PKS (polyketides) Enumerator software, (2) the chemical diversity and distribution of structural motifs in V1M library, and (3) the unique opportunities for future virtual screening of such enumerated ensembles of macrolides. Importantly, V1M is provided in the Supplementary Material of this paper allowing other researchers to conduct any type of molecular modeling and virtual screening studies. Therefore, this technology for enumerating extremely large libraries of macrolide scaffolds could hold a unique potential in the field of computational chemistry and drug discovery for rational designing of new antibiotics and anti-cancer agents. DA - 2018/11/12/ PY - 2018/11/12/ DO - 10.1186/s13321-018-0307-6 VL - 10 SP - SN - 1758-2946 ER - TY - JOUR TI - Predicting Adverse Drug Effects from Literature- and Database-Mined Assertions AU - La, Mary K. AU - Sedykh, Alexander AU - Fourches, Denis AU - Muratov, Eugene AU - Tropsha, Alexander T2 - DRUG SAFETY AB - Given that adverse drug effects (ADEs) have led to post-market patient harm and subsequent drug withdrawal, failure of candidate agents in the drug development process, and other negative outcomes, it is essential to attempt to forecast ADEs and other relevant drug–target–effect relationships as early as possible. Current pharmacologic data sources, providing multiple complementary perspectives on the drug–target–effect paradigm, can be integrated to facilitate the inference of relationships between these entities. This study aims to identify both existing and unknown relationships between chemicals (C), protein targets (T), and ADEs (E) based on evidence in the literature. Cheminformatics and data mining approaches were employed to integrate and analyze publicly available clinical pharmacology data and literature assertions interrelating drugs, targets, and ADEs. Based on these assertions, a C–T–E relationship knowledge base was developed. Known pairwise relationships between chemicals, targets, and ADEs were collected from several pharmacological and biomedical data sources. These relationships were curated and integrated according to Swanson’s paradigm to form C–T–E triangles. Missing C–E edges were then inferred as C–E relationships. Unreported associations between drugs, targets, and ADEs were inferred, and inferences were prioritized as testable hypotheses. Several C–E inferences, including testosterone → myocardial infarction, were identified using inferences based on the literature sources published prior to confirmatory case reports. Timestamping approaches confirmed the predictive ability of this inference strategy on a larger scale. The presented workflow, based on free-access databases and an association-based inference scheme, provided novel C–E relationships that have been validated post hoc in case reports. With refinement of prioritization schemes for the generated C–E inferences, this workflow may provide an effective computational method for the early detection of potential drug candidate ADEs that can be followed by targeted experimental investigations. DA - 2018/11// PY - 2018/11// DO - 10.1007/s40264-018-0688-5 VL - 41 IS - 11 SP - 1059-1072 SN - 1179-1942 ER - TY - JOUR TI - Relation of contaminants to fish intersex in riverine sport fishes AU - Grieshaber, Casey A. AU - Penland, Tiffany N. AU - Kwak, Thomas J. AU - Cope, W. Gregory AU - Heise, Ryan J. AU - Mac Law, J. AU - Shea, Damian AU - Aday, D. Derek AU - Rice, James A. AU - Kullman, Seth W. T2 - SCIENCE OF THE TOTAL ENVIRONMENT AB - Endocrine active compounds (EACs) are pollutants that have been recognized as an emerging and widespread threat to aquatic ecosystems globally. Intersex, the presence of female germ cells within a predominantly male gonad, is considered a biomarker of endocrine disruption caused by EACs. We measured a suite of EACs and assessed their associated impacts on fish intersex occurrence and severity in a large, regulated river system in North Carolina and South Carolina, USA. Our specific objective was to determine the relationship of contaminants in water, sediment, and fish tissue with the occurrence and severity of the intersex condition in wild, adult black bass (Micropterus), sunfish (Lepomis), and catfish (Ictaluridae) species at 11 sites located on the Yadkin-Pee Dee River. Polycyclic aromatic hydrocarbons (PAHs), ethinylestradiol (EE2), and heavy metals were the most prevalent contaminants that exceeded effect levels for the protection of aquatic organisms. Fish intersex condition was most frequently observed and most severe in black basses and was less frequently detected and less severe in sunfishes and catfishes. The occurrence of the intersex condition in fish showed site-related effects, rather than increasing longitudinal trends from upstream to downstream. Mean black bass and catfish tissue contaminant concentrations were higher than that of sunfish, likely because of the latter's lower trophic position in the food web. Principal component analysis identified waterborne PAHs as the most correlated environmental contaminant with intersex occurrence and severity in black bass and sunfish. As indicated by the intersex condition, EACs have adverse but often variable effects on the health of wild sport fishes in this river, likely due to fluctuations in EAC inputs and the dynamic nature of the riverine system. These findings enhance the understanding of the relationship between contaminants and fish health and provide information to guide ecologically comprehensive conservation and management decisions. DA - 2018/12/1/ PY - 2018/12/1/ DO - 10.1016/j.scitotenv.2018.06.071 VL - 643 SP - 73-89 SN - 1879-1026 KW - Endocrine active compounds KW - Endocrine disruption KW - Bass KW - Polycyclic aromatic hydrocarbons KW - Ethinylestradiol KW - Mercury ER - TY - JOUR TI - Duality of estrogen receptor beta action in cancer progression AU - Guillette, T. C. AU - Jackson, Thomas W. AU - Belcher, Scott M. T2 - CURRENT OPINION IN PHARMACOLOGY AB - The physiological actions of estrogens are primarily mediated by the nuclear hormone receptors estrogen receptor alpha (ERα) and beta (ERβ). Activities of these nuclear steroid hormone receptors in etiology and progression of many hormone-responsive cancers are well-established, yet the specific role of each receptor, and their various expressed isoforms, in estrogen-responsive cancers remains unclear. Recent advances in nuclear receptor profiling, characterization of expressed splice variants, and the availability of new experimental cancer models, has extended the understanding of the complex interplay between the differentially expressed nuclear estrogen receptors. In this review, we discuss proposed roles of ERβ in several subtypes of cancers that lack significant ERα expression and define current understanding of how different ERs collaborate to regulate cellular processes. DA - 2018/8// PY - 2018/8// DO - 10.1016/j.coph.2018.05.001 VL - 41 SP - 66-73 SN - 1471-4973 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85047091078&partnerID=MN8TOARS ER - TY - JOUR TI - Chemical-Induced Phenotypes at CTD Help Inform the Predisease State and Construct Adverse Outcome Pathways AU - Davis, Allan Peter AU - Wiegers, Thomas C. AU - Wiegers, Jolene AU - Johnson, Robin J. AU - Sciaky, Daniela AU - Grondin, Cynthia J. AU - Mattingly, Carolyn J. T2 - TOXICOLOGICAL SCIENCES AB - The Comparative Toxicogenomics Database (CTD; http://ctdbase.org) is a public resource that manually curates the scientific literature to provide content that illuminates the molecular mechanisms by which environmental exposures affect human health. We introduce our new chemical-phenotype module that describes how chemicals can affect molecular, cellular, and physiological phenotypes. At CTD, we operationally distinguish between phenotypes and diseases, wherein a phenotype refers to a nondisease biological event: eg, decreased cell cycle arrest (phenotype) versus liver cancer (disease), increased fat cell proliferation (phenotype) versus morbid obesity (disease), etc. Chemical-phenotype interactions are expressed in a formal structured notation using controlled terms for chemicals, phenotypes, taxon, and anatomical descriptors. Combining this information with CTD’s chemical-disease module allows inferences to be made between phenotypes and diseases, yielding potential insight into the predisease state. Integration of all 4 CTD modules furnishes unique opportunities for toxicologists to generate computationally predictive adverse outcome pathways, linking chemical-gene molecular initiating events with phenotypic key events, adverse diseases, and population-level health outcomes. As examples, we present 3 diverse case studies discerning the effect of vehicle emissions on altered leukocyte migration, the role of cadmium in influencing phenotypes preceding Alzheimer disease, and the connection of arsenic-induced glucose metabolic phenotypes with diabetes. To date, CTD contains over 165 000 interactions that connect more than 6400 chemicals to 3900 phenotypes for 760 anatomical terms in 215 species, from over 19 000 scientific articles. To our knowledge, this is the first comprehensive set of manually curated, literature-based, contextualized, chemical-induced, nondisease phenotype data provided to the public. DA - 2018/9// PY - 2018/9// DO - 10.1093/toxsci/kfy131 VL - 165 IS - 1 SP - 145-156 SN - 1096-0929 KW - phenotype KW - database KW - curation KW - chemical KW - disease KW - adverse outcome pathway ER - TY - JOUR TI - Confirmation of high-throughput screening data and novel mechanistic insights into VDR-xenobiotic interactions by orthogonal assays AU - Mahapatra, Debabrata AU - Franzosa, Jill A. AU - Roell, Kyle AU - Kuenemann, Melaine Agnes AU - Houck, Keith A. AU - Reif, David M. AU - Fourches, Denis AU - Kullman, Seth W. T2 - Scientific Reports AB - High throughput screening (HTS) programs have demonstrated that the Vitamin D receptor (VDR) is activated and/or antagonized by a wide range of structurally diverse chemicals. In this study, we examined the Tox21 qHTS data set generated against VDR for reproducibility and concordance and elucidated functional insights into VDR-xenobiotic interactions. Twenty-one potential VDR agonists and 19 VDR antagonists were identified from a subset of >400 compounds with putative VDR activity and examined for VDR functionality utilizing select orthogonal assays. Transient transactivation assay (TT) using a human VDR plasmid and Cyp24 luciferase reporter construct revealed 20/21 active VDR agonists and 18/19 active VDR antagonists. Mammalian-2-hybrid assay (M2H) was then used to evaluate VDR interactions with co-activators and co-regulators. With the exception of a select few compounds, VDR agonists exhibited significant recruitment of co-regulators and co-activators whereas antagonists exhibited considerable attenuation of recruitment by VDR. A unique set of compounds exhibiting synergistic activity in antagonist mode and no activity in agonist mode was identified. Cheminformatics modeling of VDR-ligand interactions were conducted and revealed selective ligand VDR interaction. Overall, data emphasizes the molecular complexity of ligand-mediated interactions with VDR and suggest that VDR transactivation may be a target site of action for diverse xenobiotics. DA - 2018/6/11/ PY - 2018/6/11/ DO - 10.1038/S41598-018-27055-3 VL - 8 IS - 1 J2 - Sci Rep LA - en OP - SN - 2045-2322 UR - http://dx.doi.org/10.1038/S41598-018-27055-3 DB - Crossref ER - TY - JOUR TI - Case study comparison of functional vs. organic stability approaches for assessing threat potential at closed landfills in the USA AU - Sean T. O'Donnell, AU - Caldwell, Michael D. AU - Barlaz, Morton A. AU - Morris, Jeremy W. F. T2 - WASTE MANAGEMENT AB - Municipal solid waste (MSW) landfills in the USA are regulated under Subtitle D of the Resource Conservation and Recovery Act (RCRA), which includes the requirement to protect human health and the environment (HHE) during the post-closure care (PCC) period. Several approaches have been published for assessment of potential threats to HHE. These approaches can be broadly divided into organic stabilization, which establishes an inert waste mass as the ultimate objective, and functional stability, which considers long-term emissions in the context of minimizing threats to HHE in the absence of active controls. The objective of this research was to conduct a case study evaluation of a closed MSW landfill using long-term data on landfill gas (LFG) production, leachate quality, site geology, and solids decomposition. Evaluations based on both functional and organic stability criteria were compared. The results showed that longer periods of LFG and leachate management would be required using organic stability criteria relative to an approach based on functional stability. These findings highlight the somewhat arbitrary and overly stringent nature of assigning universal stability criteria without due consideration of the landfill’s hydrogeologic setting and potential environmental receptors. This supports previous studies that advocated for transition to a passive or inactive control stage based on a performance-based functional stability framework as a defensible mechanism for optimizing and ending regulatory PCC. DA - 2018/5// PY - 2018/5// DO - 10.1016/j.wasman.2018.02.001 VL - 75 SP - 415-426 SN - 1879-2456 KW - Post-closure care KW - Leachate KW - Landfill gas KW - Settlement KW - EPCC methodology ER - TY - PCOMM TI - Raw milk consumption and other early-life farm exposures and adult pulmonary function in the Agricultural Lung Health Study AU - Wyss, Annah B. AU - House, John S. AU - Hoppin, Jane A. AU - Richards, Marie AU - Hankinson, John L. AU - Long, Stuart AU - Henneberger, Paul K. AU - Freeman, Laura E. Beane AU - Sandler, Dale P. AU - O'Connell, Elizabeth Long AU - Cummings, Christie Barker AU - Umbach, David M. AU - London, Stephanie J. AB - Literature suggests that early exposure to the farming environment protects against atopy and asthma; few studies have examined pulmonary function. We evaluated associations between early-life farming exposures and pulmonary function in 3061 adults (mean age=63) from a US farming population using linear regression. Childhood raw milk consumption was associated with higher FEV 1 (β=49.5 mL, 95% CI 2.8 to 96.1 mL, p=0.04) and FVC (β=66.2 mL, 95% CI 13.2 to 119.1 mL, p=0.01). We did not find appreciable associations with other early-life farming exposures. We report a novel association between raw milk consumption and higher pulmonary function that lasts into older adulthood. DA - 2018/3// PY - 2018/3// DO - 10.1136/thoraxjnl-2017-210031 SP - 279-282 KW - COPD epidemiology KW - Asthma Epidemiology KW - Allergic lung disease KW - Occupational Lung Disease KW - Respiratory Measurement ER - TY - JOUR TI - Prenatal Phthalates, Maternal Thyroid Function, and Risk of Attention-Deficit Hyperactivity Disorder in the Norwegian Mother and Child Cohort AU - Engel, Stephanie M. AU - Villanger, Gro D. AU - Nethery, Rachel C. AU - Thomsen, Cathrine AU - Sakhi, Amrit K. AU - Drover, Samantha S. M. AU - Hoppin, Jane A. AU - Zeiner, Pal AU - Knudsen, Gun Peggy AU - Reichborn-Kjennerud, Ted AU - Herring, Amy H. AU - Aase, Heidi T2 - ENVIRONMENTAL HEALTH PERSPECTIVES AB - There is growing concern that phthalate exposures may have an impact on child neurodevelopment. Prenatal exposure to phthalates has been linked with externalizing behaviors and executive functioning defects suggestive of an attention-deficit hyperactivity disorder (ADHD) phenotype.We undertook an investigation into whether prenatal exposure to phthalates was associated with clinically confirmed ADHD in a population-based nested case-control study of the Norwegian Mother and Child Cohort (MoBa) between the years 2003 and 2008.Phthalate metabolites were measured in maternal urine collected at midpregnancy. Cases of ADHD (n=297) were obtained through linkage between MoBa and the Norwegian National Patient Registry. A random sample of controls (n=553) from the MoBa population was obtained.In multivariable adjusted coexposure models, the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP) was associated with a monotonically increasing risk of ADHD. Children of mothers in the highest quintile of ∑DEHP had almost three times the odds of an ADHD diagnosis as those in the lowest [OR=2.99 (95% CI: 1.47, 5.49)]. When ∑DEHP was modeled as a log-linear (natural log) term, for each log-unit increase in exposure, the odds of ADHD increased by 47% [OR=1.47 (95% CI: 1.09, 1.94)]. We detected no significant modification by sex or mediation by prenatal maternal thyroid function or by preterm delivery.In this population-based case-control study of clinical ADHD, maternal urinary concentrations of DEHP were monotonically associated with increased risk of ADHD. Additional research is needed to evaluate potential mechanisms linking phthalates to ADHD. https://doi.org/10.1289/EHP2358. DA - 2018/5// PY - 2018/5// DO - 10.1289/ehp2358 VL - 126 IS - 5 SP - SN - 1552-9924 ER - TY - JOUR TI - Microbial ecological succession during municipal solid waste decomposition AU - Staley, Bryan F. AU - de los Reyes, Francis L. AU - Wang, Ling AU - Barlaz, Morton A. T2 - Applied Microbiology and Biotechnology DA - 2018/4/28/ PY - 2018/4/28/ DO - 10.1007/s00253-018-9014-5 VL - 102 IS - 13 SP - 5731-5740 J2 - Appl Microbiol Biotechnol LA - en OP - SN - 0175-7598 1432-0614 UR - http://dx.doi.org/10.1007/s00253-018-9014-5 DB - Crossref KW - Anerobic KW - Landfill KW - Microbial community KW - 16S rRNA gene KW - Refuse decomposition KW - MSW ER - TY - JOUR TI - Characterizing the effects of missing data and evaluating imputation methods for chemical prioritization applications using ToxPi AU - To, Kimberly T. AU - Fry, Rebecca C. AU - Reif, David M. T2 - BIODATA MINING AB - The Toxicological Priority Index (ToxPi) is a method for prioritization and profiling of chemicals that integrates data from diverse sources. However, individual data sources ("assays"), such as in vitro bioassays or in vivo study endpoints, often feature sections of missing data, wherein subsets of chemicals have not been tested in all assays. In order to investigate the effects of missing data and recommend solutions, we designed simulation studies around high-throughput screening data generated by the ToxCast and Tox21 programs on chemicals highlighted by the Agency for Toxic Substances and Disease Registry's (ATSDR) Substance Priority List (SPL), which helps prioritize environmental research and remediation resources.Our simulations explored a wide range of scenarios concerning data (0-80% assay data missing per chemical), modeling (ToxPi models containing from 160-700 different assays), and imputation method (k-Nearest-Neighbor, Max, Mean, Min, Binomial, Local Least Squares, and Singular Value Decomposition). We find that most imputation methods result in significant changes to ToxPi score, except for datasets with a small number of assays. If we consider rank change conditional on these significant changes to ToxPi score, we find that ranks of chemicals in the minimum value imputation, SVD imputation, and kNN imputation sets are more sensitive to the score changes.We found that the choice of imputation strategy exerted significant influence over both scores and associated ranks, and the most sensitive scenarios were those involving fewer assays plus higher proportions of missing data. By characterizing the effects of missing data and the relative benefit of imputation approaches across real-world data scenarios, we can augment confidence in the robustness of decisions regarding the health and ecological effects of environmental chemicals. DA - 2018/6/13/ PY - 2018/6/13/ DO - 10.1186/s13040-018-0169-5 VL - 11 IS - 1 SP - SN - 1756-0381 UR - https://doi.org/10.1186/s13040-018-0169-5 KW - Chemical prioritization KW - ToxPi KW - ToxCast KW - Missing data KW - Imputation KW - Multiple imputation KW - Simulation ER - TY - JOUR TI - Application of a life cycle model for european union policy-driven waste management decision making in emerging economies AU - Stanisavljevic, N. AU - Levis, J. W. AU - Barlaz, M. A. T2 - Journal of Industrial Ecology AB - Summary Solid waste life cycle modeling has predominantly focused on developed countries, but there are significant opportunities to assist developing and transition economies to minimize the environmental impact of solid waste management (SWM). Serbia is representative of a transition country and most (92%) of its waste is landfilled. As a Candidate European Union (EU) country, Serbia is expected to implement SWM strategies that meet EU directives. The Solid Waste Life‐Cycle Optimization Framework (SWOLF) was used to evaluate scenarios that meet EU goals by 2030. Scenarios included combinations of landfills, anaerobic digestion, composting, material recovery facilities (MRFs), waste‐to‐energy (WTE) combustion, and the use of refuse‐derived fuel in cement kilns. Each scenario was evaluated with and without separate collection of recyclables. Modeled impacts included cost, climate change, cumulative fossil energy demand, acidification, eutrophication, photochemical oxidation, total eco‐toxicity, and total human toxicity. Trade‐offs among the scenarios were evaluated because no scenario performed best in every category. In general, SWM strategies that incorporated processes that recover energy and recyclable materials performed well across categories, whereas scenarios that did not include energy recovery performed poorly. Emissions offsets attributable to energy recovery and reduced energy requirements associated with remanufacturing of recovered recyclables had the strongest influence on the results. The scenarios rankings were robust under parametric sensitivity analysis, except when the marginal electricity fuel source changed from coal to natural gas. Model results showed that the use of existing infrastructure, energy recovery, and efficient recovery of recyclables from mixed waste can reduce environmental emissions at relatively low cost. DA - 2018/// PY - 2018/// DO - 10.1111/jiec.12564 VL - 22 IS - 2 SP - 341-355 ER - TY - JOUR TI - Use of a specific polyclonal anti-canine TSLP antibody reveals TSLP expression in normal tissue and cell culture AU - Ganchingco, J. R. C. AU - Yoder, J. A. AU - Baumer, W. T2 - Journal of Veterinary Pharmacology and Therapeutics DA - 2018/// PY - 2018/// VL - 41 SP - 153-153 ER - TY - JOUR TI - Janus kinase inhibitors differ in their affinity to the TRPV1 receptor - implications for their use in itch and pain AU - Sanabria-Ojeda, L. AU - Fukuyama, T. AU - Fourches, D. AU - Baumer, W. T2 - Journal of Veterinary Pharmacology and Therapeutics DA - 2018/// PY - 2018/// VL - 41 SP - 160-160 ER - TY - JOUR TI - In silico Predicted Glucose-1-phosphate Uridylyltransferase (GalU) Inhibitors Block a Key Pathway Required for Listeria Virulence AU - Kuenemann, Melaine A. AU - Spears, Patricia A. AU - Orndorff, Paul E. AU - Fourches, Denis T2 - Molecular Informatics AB - Peptidoglycan walls of gram positive bacteria are functionalized by glycopolymers called wall teichoic acid (WTA). In Listeria monocytogenes, multiple enzymes including the glucose-1-phosphate uridylyltransferase (GalU) were identified as mandatory for WTA galactosylation, so that the inhibition of GalU is associated with a significant attenuation of Listeria virulence. Herein, we report on a series of in silico predicted GalU inhibitors identified using structure-based virtual screening and experimentally validated to be effective in blocking the WTA galactosylation pathway in vitro. Several hits such as C04, a pyrimidinyl benzamide, afforded promising experimental potencies. This proof-of-concept study opens new perspectives for the development of potent and selective GalU inhibitors of high interest to attenuate Listeria virulence. It also underscores the high relevance of using molecular modeling for facilitating the identification of bacterial virulence attenuators and more generally antibacterials. DA - 2018/3/8/ PY - 2018/3/8/ DO - 10.1002/MINF.201800004 VL - 37 IS - 6-7 SP - 1800004 J2 - Mol. Inf. LA - en OP - SN - 1868-1743 UR - http://dx.doi.org/10.1002/MINF.201800004 DB - Crossref KW - drug design KW - molecular modeling KW - structure-activity relationships KW - virtual screening KW - antibiotics ER - TY - JOUR TI - Improving wood properties for wood utilization through multi-omics integration in lignin biosynthesis AU - Wang, Jack P. AU - Matthews, Megan L. AU - Williams, Cranos M. AU - Shi, Rui AU - Yang, Chenmin AU - Tunlaya-Anukit, Sermsawat AU - Chen, Hsi-Chuan AU - Li, Quanzi AU - Liu, Jie AU - Lin, Chien-Yuan AU - Naik, Punith AU - Sun, Ying-Hsuan AU - Loziuk, Philip L. AU - Yeh, Ting-Feng AU - Kim, Hoon AU - Gjersing, Erica AU - Shollenberger, Todd AU - Shuford, Christopher M. AU - Song, Jina AU - Miller, Zachary AU - Huang, Yung-Yun AU - Edmunds, Charles W. AU - Liu, Bao-Guang AU - Sun, Yi AU - Lin, Ying-Chung AU - Li, Wei AU - Chen, Hao AU - Peszlen, Ilona AU - Ducoste, Joel AU - Ralph, John AU - Chang, Hou-Min AU - Muddiman, David C. AU - Davis, Mark F. AU - Smith, Chris AU - Isik, Fikret AU - Sederoff, Ronald AU - Chiang, Vincent T2 - Nature Communications AB - A multi-omics quantitative integrative analysis of lignin biosynthesis can advance the strategic engineering of wood for timber, pulp, and biofuels. Lignin is polymerized from three monomers (monolignols) produced by a grid-like pathway. The pathway in wood formation of Populus trichocarpa has at least 21 genes, encoding enzymes that mediate 37 reactions on 24 metabolites, leading to lignin and affecting wood properties. We perturb these 21 pathway genes and integrate transcriptomic, proteomic, fluxomic and phenomic data from 221 lines selected from ~2000 transgenics (6-month-old). The integrative analysis estimates how changing expression of pathway gene or gene combination affects protein abundance, metabolic-flux, metabolite concentrations, and 25 wood traits, including lignin, tree-growth, density, strength, and saccharification. The analysis then predicts improvements in any of these 25 traits individually or in combinations, through engineering expression of specific monolignol genes. The analysis may lead to greater understanding of other pathways for improved growth and adaptation. DA - 2018/12// PY - 2018/12// DO - 10.1038/s41467-018-03863-z VL - 9 IS - 1 SP - 1579 SN - 2041-1723 ER - TY - JOUR TI - Cheminformatics Analysis of Dynamic WNK-Inhibitor Interactions AU - Kuenemann, Melaine A. AU - Fourches, Denis T2 - Molecular Informatics AB - Abstract The With‐No‐Lysine (WNK) serine/threonine kinase family constitutes a unique and distinctive branch of the kinome. The four proteins of this family (WNK1/2/3/4) are involved in blood pressure regulation, body fluid, and electrolyte homeostasis. Herein, we modeled and analyzed the binding modes of all publicly‐available small orthosteric and allosteric binders (including WNK463 and WNK467) experimentally tested towards any of the WNK family member. To do so, we relied on state‐of‐the‐art cheminformatics approaches including structure‐based molecular docking and molecular dynamics simulations. In particular, we computed and analyzed the (i) molecular selectivity of known inhibitors when docked in the binding site of each WNK family member, (ii) the dynamic WNK‐inhibitor interactions at both orthosteric and allosteric sites to derive new structure‐activity relationships, and (iii) the key specific interactions present in each binding site. This study reports on the first, cheminformatics‐powered analysis of the entire chemical space of known WNK inhibitors. We discuss the conservation of critical WNK‐inhibitor interactions and the existence of isoform‐specific interactions that could enable the rational design of more potent and selective WNK binders. DA - 2018/2/23/ PY - 2018/2/23/ DO - 10.1002/MINF.201700138 VL - 37 IS - 6-7 SP - 1700138 J2 - Mol. Inf. LA - en OP - SN - 1868-1743 UR - http://dx.doi.org/10.1002/MINF.201700138 DB - Crossref KW - drug design KW - kinases KW - medicinal chemistry KW - structure-activity relationships KW - molecular modeling ER - TY - JOUR TI - An object-oriented Bayesian network approach for establishing swine manure-borne natural estrogenic compounds budget AU - Lee, Boknam AU - Kullman, Sethw. AU - Yost, Erin E. AU - Worley-Davis, Lynn AU - Reckhow, Kenneth H. T2 - SCIENCE OF THE TOTAL ENVIRONMENT AB - A facility-wide estrogen budget model was developed to assess the excretion of natural estrogens by swine in a commercial swine farrowing concentrated animal feeding operations (CAFO) in North Carolina, using an object-oriented Bayesian network (OOBN) approach. The OOBN model is the combination of twelve objects of Bayesian network models, which characterize the estrogen budget flows based on the sow reproductive cycle (i.e., pre-estrus, estrus, and lactation) for the three natural estrogen types [estrone (E1), 17β-estradiol (E2), and estriol (E3)] within each barn. This OOBN model provides a mechanism to quantify the levels of the natural estrogens and their probabilistic distributions with regard to estrogen type, waste sources such as urine, feces, and recycling lagoon slurry, and animal reproductive status. Moreover, the OOBN model allows us to assess the overall contribution of natural estrogen compounds from each operational unit of the CAFO, while accounting for the uncertainties. Results from the OOBN model indicate a rank order of lactating sows > gestating sows > breeding sows in terms of contribution of estrogen loads to the total natural estrogen budget. As to estrogen type, E1 was found as the major estrogen metabolite with the summed concentrations of urine, feces, and flushing slurry wastes exceeding 3000 ng/l > 90% of the time. As to waste sources, the flushing slurry waste was found to be a major contributor of the estrogen budget compared with urine and feces wastes from barn animals. DA - 2018/10/15/ PY - 2018/10/15/ DO - 10.1016/j.scitotenv.2018.05.209 VL - 639 SP - 815-825 SN - 1879-1026 KW - Natural estrogens KW - Swine CAFO KW - Total facility estrogen budget KW - OOBN ER - TY - JOUR TI - Use of high-throughput in vitro toxicity screening data in cancer hazard evaluations by IARC Monograph Working Groups. AU - Chiu, WA AU - Guyton, KZ AU - Martin, MT AU - Reif, DM AU - Rusyn, I T2 - ALTEX AB - Evidence regarding carcinogenic mechanisms serves a critical role in International Agency for Research on Cancer (IARC) Monograph evaluations. Three recent IARC Working Groups pioneered inclusion of the US Environmental Protection Agency (EPA) ToxCast program high-throughput screening (HTS) data to supplement other mechanistic evidence. In Mono­graph V110, HTS profiles were compared between perfluorooctanoic acid (PFOA) and prototypical activators across multiple nuclear receptors. For Monograph V112-113, HTS assays were mapped to 10 key characteristics of carcinogens identified by an IARC expert group, and systematically considered as an additional mechanistic data stream. Both indi­vidual assay results and ToxPi-based rankings informed mechanistic evaluations. Activation of multiple nuclear receptors in HTS assays showed that PFOA targets not only peroxisome proliferator activated receptors, but also other receptors. ToxCast assays substantially covered 5 of 10 key characteristics, corroborating literature evidence of “induces oxidative stress” and “alters cell proliferation, cell death or nutrient supply” and filling gaps for “modulates receptor-mediated effects.” Thus, ToxCast HTS data were useful both in evaluating specific mechanistic hypotheses and in contributing to the overall evaluation of mechanistic evidence. However, additional HTS assays are needed to provide more comprehensive coverage of the 10 key characteristics of carcinogens that form the basis of current IARC mechanistic evaluations. DA - 2018/// PY - 2018/// DO - 10.14573/altex.1703231 VL - 35 IS - 1 SP - 51-64 UR - http://europepmc.org/abstract/med/28738424 KW - carcinogenicity KW - high throughput screening KW - in vitro KW - mechanisms ER - TY - JOUR TI - The neurological toxicity of heavy metals: A fish perspective AU - Green, Adrian J. AU - Planchart, Antonio T2 - Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology AB - The causes of neurodegenerative diseases are complex with likely contributions from genetic susceptibility and environmental exposures over an organism's lifetime. In this review, we examine the role that aquatic models, especially zebrafish, have played in the elucidation of mechanisms of heavy metal toxicity and nervous system function over the last decade. Focus is applied to cadmium, lead, and mercury as significant contributors to central nervous system morbidity, and the application of numerous transgenic zebrafish expressing fluorescent reporters in specific neuronal populations or brain regions enabling high-resolution neurodevelopmental and neurotoxicology research. DA - 2018/6// PY - 2018/6// DO - 10.1016/j.cbpc.2017.11.008 VL - 208 SP - 12-19 J2 - Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology LA - en OP - SN - 1532-0456 UR - http://dx.doi.org/10.1016/j.cbpc.2017.11.008 DB - Crossref ER - TY - JOUR TI - Quantitative mass spectrometry imaging of glutathione in healthy and cancerous hen ovarian tissue sections by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) AU - Nazari, Milad AU - Bokhart, Mark T. AU - Loziuk, Philip L. AU - Muddiman, David C. T2 - ANALYST AB - IR-MALDESI quantitative mass spectrometry imaging of glutathione in healthy and cancerous hen ovarian tissues. DA - 2018/2/7/ PY - 2018/2/7/ DO - 10.1039/c7an01828b VL - 143 IS - 3 SP - 654-661 SN - 1364-5528 ER - TY - JOUR TI - Predicting characteristics of rainfall driven estrogen runoff and transport from swine AFO spray fields (vol 532, pg 571, 2015) AU - Lee, Boknam AU - Kullman, Seth W. AU - Yost, Erin E. AU - Meyer, Michael T. AU - Worley-Davis, Lynn AU - Williams, C. Michael AU - Reckhow, Kenneth H. T2 - SCIENCE OF THE TOTAL ENVIRONMENT DA - 2018/7/1/ PY - 2018/7/1/ DO - 10.1016/j.scitotenv.2018.02.141 VL - 628-629 SP - 1460-1460 SN - 1879-1026 ER - TY - JOUR TI - Maternal vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years AU - Neelon, S. E. Benjamin AU - White, A. J. AU - Vidal, A. C. AU - Schildkraut, J. M. AU - Murtha, A. P. AU - Murphy, S. K. AU - Kullman, S. W. AU - Hoyo, C. T2 - INTERNATIONAL JOURNAL OF OBESITY AB - Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring. We conducted linear regressions to assess maternal plasma 25-hydroxyvitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10. Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l−m at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores (−0.43 units; CI: −0.79, −0.07; P=0.02 for Q1 and −0.56 units; CI: −0.89, −0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing. Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined. DA - 2018/4// PY - 2018/4// DO - 10.1038/ijo.2017.160 VL - 42 IS - 4 SP - 587-593 SN - 1476-5497 ER - TY - JOUR TI - The decay of engineered wood products and paper excavated from landfills in Australia AU - Ximenes, Fabiano A. AU - Cowie, Annette L. AU - Barlaz, Morton A. T2 - WASTE MANAGEMENT AB - Large volumes of engineered wood products (EWPs) and paper are routinely placed in landfills in Australia, where they are assumed to decay. However, the extent of decay for EWPs is not well-known. This study reports carbon loss from EWPs and paper buried in landfills in Sydney, Brisbane and Cairns in Australia, located in temperate, subtropical and tropical climates, respectively. The influence of pulp type (mechanical and chemical) and landfill type (municipal solid waste - MSW and construction and demolition - C&D) on decay levels were investigated. Carbon loss for EWPs ranged from 0.6 to 9.0%; though there is some uncertainty in these values due to limitations associated with sourcing appropriate controls. Carbon loss for paper products ranged from 0 to 58.9%. Papers produced from predominantly mechanical pulps generally had lower levels of decay than those produced via chemical or partly chemical processes. Typically, decay levels for paper products were highest for the tropical Cairns landfill, suggesting that climate may be a significant factor to be considered when estimating emissions from paper in landfills. For EWPs, regardless of the landfill type and climate, carbon losses were low, confirming results from previous laboratory studies. Lower carbon losses were observed for EWP and paper excavated from the Sydney C&D landfill, compared with the Sydney MSW landfill, confirming the hypothesis that conditions in C&D landfills are less favourable for decay. These results have implications for greenhouse gas inventory estimations, as carbon losses for EWPs were lower than the commonly assumed values of 23% (US EPA) and 50% (Intergovernmental Panel on Climate Change). For paper types, we suggest that separate decay factors should be used for papers dominated by mechanical pulp and those produced from mostly chemical pulps, and also for papers buried in tropical or more temperate climates. DA - 2018/4// PY - 2018/4// DO - 10.1016/j.wasman.2017.11.035 VL - 74 SP - 312-322 SN - 1879-2456 KW - Landfill KW - Paper KW - Engineered wood products KW - Carbon KW - Decay ER - TY - JOUR TI - IR-MALDESI method optimization based on time-resolved measurement of ion yields AU - Ekeloef, Mans AU - Muddiman, David C. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY DA - 2018/1// PY - 2018/1// DO - 10.1007/s00216-017-0585-2 VL - 410 IS - 3 SP - 963-970 SN - 1618-2650 KW - IR-MALDESI KW - Electrospray post-ionization KW - Mass spectrometry imaging KW - Laser ablation KW - Q Exactive ER - TY - JOUR TI - Direct analysis of terpenes from biological buffer systems using SESI and IR-MALDESI AU - Nazari, Milad AU - Malico, Alexandra A. AU - Ekeloef, Mans AU - Lund, Sean AU - Williams, Gavin J. AU - Muddiman, David C. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY DA - 2018/1// PY - 2018/1// DO - 10.1007/s00216-017-0570-9 VL - 410 IS - 3 SP - 953-962 SN - 1618-2650 KW - Terpenes KW - IR-MALDESI KW - SESI KW - Direct analysis KW - Biological buffers KW - Q Exactive Plus ER - TY - JOUR TI - Adverse drug reactions triggered by the common HLA-B*57:01 variant: Virtual screening of DrugBank using 3D molecular docking AU - Van Den Driessche, G. AU - Fourches, D. T2 - Journal of Cheminformatics DA - 2018/// PY - 2018/// VL - 10 ER - TY - JOUR TI - ToxPi Graphical User Interface 2.0: Dynamic exploration, visualization, and sharing of integrated data models. AU - Marvel, SW AU - To, K AU - Grimm, FA AU - Wright, FA AU - Rusyn, I AU - Reif, DM T2 - BMC bioinformatics AB - Drawing integrated conclusions from diverse source data requires synthesis across multiple types of information. The ToxPi (Toxicological Prioritization Index) is an analytical framework that was developed to enable integration of multiple sources of evidence by transforming data into integrated, visual profiles. Methodological improvements have advanced ToxPi and expanded its applicability, necessitating a new, consolidated software platform to provide functionality, while preserving flexibility for future updates.We detail the implementation of a new graphical user interface for ToxPi (Toxicological Prioritization Index) that provides interactive visualization, analysis, reporting, and portability. The interface is deployed as a stand-alone, platform-independent Java application, with a modular design to accommodate inclusion of future analytics. The new ToxPi interface introduces several features, from flexible data import formats (including legacy formats that permit backward compatibility) to similarity-based clustering to options for high-resolution graphical output.We present the new ToxPi interface for dynamic exploration, visualization, and sharing of integrated data models. The ToxPi interface is freely-available as a single compressed download that includes the main Java executable, all libraries, example data files, and a complete user manual from http://toxpi.org . DA - 2018/3// PY - 2018/3// DO - 10.1186/s12859-018-2089-2 VL - 3 IS - 1 UR - http://europepmc.org/abstract/med/29506467 KW - Visual analytics KW - Software KW - systems biology KW - Risk assessment KW - Data integration KW - Graphical user interface ER - TY - JOUR TI - Endotoxin enhances respiratory effects of phthalates in adults: Results from NHANES 2005-6 AU - Strassle, Paula D. AU - Smit, Lidwien A. M. AU - Hoppin, Jane A. T2 - ENVIRONMENTAL RESEARCH AB - Phthalates have been associated with respiratory symptoms in adults; they may enhance effects of inflammatory compounds. To assess the potential interactions of phthalates and endotoxin on respiratory and allergic symptoms in adults, we used cross-sectional information from the 1091 adults with complete data on urinary phthalates and house dust endotoxin from NHANES 2005–2006. We used multivariable logistic regression to assess whether endotoxin levels modified the association between nine phthalate metabolites and four current allergic symptoms (asthma, wheeze, hay fever, and rhinitis). Endotoxin was classified into tertiles (<10, 10–25, >25 EU/mg dust). Urinary phthalate and dust endotoxin levels were not correlated (r < |0.02|). Under low endotoxin conditions, no associations between phthalates and respiratory outcomes were observed. Under medium or high endotoxin conditions, exposure-response relationships were observed between specific phthalates and wheeze and asthma. For wheeze, three phthalates (mono-benzyl phthalate (MBzP), mono(carboxyoctyl) phthalate (MCOP), and di-ethylhexyl phthalate (DEHP) had significant interactions with endotoxin); for asthma, two phthalates (MCOP and mono(carboxyoctyl) phthalate (MCNP)) had significant interactions. Endotoxin did not modify the associations between phthalates and hay fever or rhinitis. These results are consistent with the hypothesis that endotoxin enhances the respiratory toxicity of phthalates; however this cross-sectional study cannot address key temporal issues. The lack of an association between wheeze or asthma and phthalates when endotoxin exposure was low suggests that phthalates alone may not increase these symptoms. DA - 2018/4// PY - 2018/4// DO - 10.1016/j.envres.2018.01.017 VL - 162 SP - 280-286 SN - 1096-0953 KW - Allergy KW - Asthma KW - Wheeze KW - Dust endotoxin KW - Phthalates ER - TY - JOUR TI - Demonstration of hydrazide tagging for O-glycans and a central composite design of experiments optimization using the INLIGHT (TM) reagent AU - King, Samuel R. AU - Hecht, Elizabeth S. AU - Muddiman, David C. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY DA - 2018/2// PY - 2018/2// DO - 10.1007/s00216-017-0828-2 VL - 410 IS - 5 SP - 1409-1415 SN - 1618-2650 KW - O-glycosylation KW - Hydrazide tag KW - Rapid derivatization KW - Design of experiments ER - TY - JOUR TI - A novel integrated strategy for the detection and quantification of the neurotoxin beta-N-methylamino-l-alanine in environmental samples AU - Beri, Joshua AU - Kirkwood, Kaylie I. AU - Muddiman, David C. AU - Bereman, Michael S. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY DA - 2018/4// PY - 2018/4// DO - 10.1007/s00216-018-0930-0 VL - 410 IS - 10 SP - 2597-2605 SN - 1618-2650 KW - BMAA KW - CZE KW - Isomer separation KW - Quantification KW - HRAM MS/MS KW - Seafood ER - TY - JOUR TI - Toward the Rational Design of Sustainable Hair Dyes Using Cheminformatics Approaches: Step 1. Database Development and Analysis AU - Williams, Tova N. AU - Kuenemann, Melaine A. AU - Driessche, George A. AU - Williams, Antony J. AU - Fourches, Denis AU - Freeman, Harold S. T2 - ACS SUSTAINABLE CHEMISTRY & ENGINEERING AB - Herein, we report on the initial step of the design process of new hair dyes with the desired properties. The first step is dedicated to the development of the largest, publicly available database of hair dye substances (containing temporary and semipermanent hair dyes as well as permanent hair dye precursors) used in commercial hair dye formulations. The database was utilized to perform a cheminformatics study assessing the computed physicochemical properties of the different hair dye substances, especially within each cluster of structurally similar dyes. The various substances could be differentiated based on their average molecular weight, hydrophobicity, topological polar surface area, and number of hydrogen bond acceptors, with some overlap also observed. In particular, we found that dyes such as C.I. Basic Orange 1 and 2 were clustered among the precursors, suggesting that their diffusion behavior is similar to that of permanent hair dye precursors. We anticipate taking advantage of this interesting knowledge in the second design phase of our investigation. As a step in that direction, we used QSAR models and noted that 65% of the substances were predicted to be mutagenic (22 with confidence thresholds >90%), whereas 79% were predicted to be skin sensitizers (37 with confidence thresholds >90%). We discuss the relevance of these preliminary calculations in view of literature-extracted experimental data. DA - 2018/2// PY - 2018/2// DO - 10.1021/acssuschemeng.7b03795 VL - 6 IS - 2 SP - 2344-2352 SN - 2168-0485 KW - Cheminformatics KW - Hair dyes KW - HDSD KW - Mutagenicity KW - Skin sensitization KW - Sustainability ER - TY - JOUR TI - Sleep apnea and pesticide exposure in a study of US farmers AU - Baumert, Brittney O. AU - Carnes, Megan Ulmer AU - Hoppin, Jane A. AU - Jackson, Chandra L. AU - Sandler, Dale P. AU - Freeman, Laura Beane AU - Henneberger, Paul K. AU - Umbach, David M. AU - Shrestha, Srishti AU - Long, Stuart AU - London, Stephanie J. T2 - SLEEP HEALTH AB - Carbamate and organophosphate pesticides inhibit acetylcholinesterase, and poisoning leads to respiratory depression. Thus, involvement in sleep apnea is plausible, but no data exist at lower levels of exposure. Other pesticides could impact sleep apnea by different mechanisms but have not been studied. Our study examines the associations between pesticide exposure and sleep apnea among pesticide applicators from a US farming population. We analyzed data from 1569 male pesticide applicators, mostly farmers, from an asthma case-control study nested within the prospective Agricultural Health Study. On questionnaires, participants reported use of specific pesticides and physician diagnosis plus prescribed treatments for sleep apnea. We used multivariable logistic regression to estimate associations between ever use of 63 pesticides and sleep apnea (234 cases, 1335 noncases). The most notable association was for carbofuran, a carbamate (100 exposed cases, odds ratio 1.83, 95% confidence interval 1.34-2.51, P = .0002). Carbofuran use began before reported onset of sleep apnea in all cases. This study adds to the known adverse health outcomes of exposure to carbofuran, a pesticide canceled in the United States in 2009 for most agricultural purposes but persists in the environment and remains in use in some other countries. We conducted the first epidemiological study investigating the association of pesticide exposure and sleep apnea. Our results in a male agricultural population suggests that exposure to carbofuran is positively associated with sleep apnea. DA - 2018/2// PY - 2018/2// DO - 10.1016/j.sleh.2017.08.006 VL - 4 IS - 1 SP - 20-26 SN - 2352-7226 KW - Pesticides KW - Sleep apnea KW - Carbofuran KW - Carbamates KW - Sleep disorder breathing KW - Agriculture ER - TY - JOUR TI - Population genetic diversity in zebrafish lines AU - Balik-Meisner, Michele AU - Truong, Lisa AU - Scholl, Elizabeth H. AU - Tanguay, Robert L. AU - Reif, David M. T2 - MAMMALIAN GENOME AB - Toxicological and pharmacological researchers have seized upon the many benefits of zebrafish, including the short generation time, well-characterized development, and early maturation as clear embryos. A major difference from many model organisms is that standard husbandry practices in zebrafish are designed to maintain population diversity. While this diversity is attractive for translational applications in human and ecological health, it raises critical questions on how interindividual genetic variation might contribute to chemical exposure or disease susceptibility differences. Findings from pooled samples of zebrafish support this supposition of diversity yet cannot directly measure allele frequencies for reference versus alternate alleles. Using the Tanguay lab Tropical 5D zebrafish line (T5D), we performed whole genome sequencing on a large group (n = 276) of individual zebrafish embryos. Paired-end reads were collected on an Illumina 3000HT, then aligned to the most recent zebrafish reference genome (GRCz10). These data were used to compare observed population genetic variation across species (humans, mice, zebrafish), then across lines within zebrafish. We found more single nucleotide polymorphisms (SNPs) in T5D than have been reported in SNP databases for any of the WIK, TU, TL, or AB lines. We theorize that some subset of the novel SNPs may be shared with other zebrafish lines but have not been identified in other studies due to the limitations of capturing population diversity in pooled sequencing strategies. We establish T5D as a model that is representative of diversity levels within laboratory zebrafish lines and demonstrate that experimental design and analysis can exert major effects when characterizing genetic diversity in heterogeneous populations. DA - 2018/2// PY - 2018/2// DO - 10.1007/s00335-018-9735-x VL - 29 IS - 1-2 SP - 90-100 SN - 1432-1777 UR - https://doi.org/10.1007/s00335-018-9735-x ER - TY - JOUR TI - Periphyton and abiotic factors influencing arsenic speciation in aquatic environments AU - Lopez, Adeline R. AU - Silva, Silmara Costa AU - Webb, Samuel M. AU - Hesterberg, Dean AU - Buchwalter, David B. T2 - ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY AB - Abstract Benthic periphytic biofilms are important food sources at the base of aquatic ecosystems. These biofilms also sit at the interface of oxic waters and hypoxic sediments, and can be influenced by or influence trace element speciation. In the present study, we compared arsenic (As) enrichment in periphyton exposed to arsenate (As[V]) or arsenite (As[III]) (20 μg/L, static renewal, 7 d), and we found similar accumulation patterns of total As (101 ± 27 and 88 ± 22 mg kg −1 dry wt, respectively). Periphyton As was 6281‐ and 6684‐fold higher than their aqueous exposures and occurred primarily as As(V). When these biofilms were fed to larval mayflies, similar total As tissue concentrations (13.9 and 14.6 mg kg −1 dry wt, respectively) were observed, revealing significant biodilution (∼ 10% of their dietary concentrations). Finally, we investigated the influence of aeration and periphyton presence on As speciation in solutions and solid phases treated with As(III). Predominantly As(III) solutions were slowly oxidized over a 7‐d time period, in the absence of periphyton, and aeration did not strongly affect oxidation rates. However, in the presence of periphyton, solution and solid‐phase analyses (by microscale x‐ray absorption spectroscopy) showed rapid As(III) oxidation to As(V) and an increasing proportion of organo‐As forming over time. Thus periphyton plays several roles in As environmental behavior: 1) decreasing total dissolved As concentrations via abiotic and biotic accumulation, 2) rapidly oxidizing As(III) to As(V), 3) effluxing organo‐As forms into solution, and 4) limiting trophic transfer to aquatic grazers. Environ Toxicol Chem 2018;37:903–913. © 2017 SETAC DA - 2018/3// PY - 2018/3// DO - 10.1002/etc.4025 VL - 37 IS - 3 SP - 903-913 SN - 1552-8618 KW - Abiotic transformation KW - Aquatic plants KW - Bioconcentration KW - Biotransformation KW - Metal speciation KW - Arsenic ER - TY - JOUR TI - Characterization of a novel miniaturized burst-mode infrared laser system for IR-MALDESI mass spectrometry imaging AU - Ekelof, Mans AU - Manni, Jeffrey, Sr. AU - Nazari, Milad AU - Bokhart, Mark AU - Muddiman, David C. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY AB - Laser systems are widely used in mass spectrometry as sample probes and ionization sources. Mid-infrared lasers are particularly suitable for analysis of high water content samples such as animal and plant tissues, using water as a resonantly excited sacrificial matrix. Commercially available mid-IR lasers have historically been bulky and expensive due to cooling requirements. This work presents a novel air-cooled miniature mid-IR laser with adjustable burst-mode output and details an evaluation of its performance for mass spectrometry imaging. The miniature laser was found capable of generating sufficient energy for complete ablation of animal tissue in the context of an IR-MALDESI experiment with exogenously added ice matrix, yielding several hundred confident metabolite identifications. DA - 2018/3// PY - 2018/3// DO - 10.1007/s00216-018-0918-9 VL - 410 IS - 9 SP - 2395-2402 SN - 1618-2650 KW - Mass spectrometry imaging KW - Infrared laser KW - IR-MALDESI KW - HRAM mass spectrometry ER - TY - JOUR TI - Spatial and temporal characteristics of elevated temperatures in municipal solid waste landfills, Navid H. Jafari, Timothy D. Stark, and Todd Thalhamer, Waste Management, 2017, Vol. 59, p. 286-301 AU - Barlaz, Morton A. AU - Benson, Craig H. AU - Castaldi, Marco AU - Luettich, Scott T2 - WASTE MANAGEMENT AB - Heat generation in municipal solid waste landfills is reviewed with a focus on extraction heat management strategy. Numerical analysis was conducted to investigate the feasibility of a vertical heat extraction system and effects of system configuration on overall performance. The modeling indicated that the influence of the extraction system on landfill temperatures is greatest near central depths of the landfill with less influence at the cover and liner locations. Temperature-depth profiles exhibited concave shapes demonstrating preferential heat extraction from central depths and return of the waste temperatures to reference conditions at great radial distance. For extraction system parameters, fluid velocity affected heat extraction more than pipe diameter; for landfill operational conditions, waste height affected heat extraction more than waste placement rate. For a fluid velocity of 0.3 m/s (threshold for turbulent flow), pipe diameter of 25.4 mm, waste height of 30 m, and waste placement rate of 20 m/year, the heat extraction rate was 59.5 MJ/m3 and the total amount of heat extracted was 561 GJ with 10 m radius of influence of the extraction well. Thermally coupled gas generation analysis indicated that regulating temperatures at 35 °C resulted in significant increases in landfill gas energy (on the order of twofold) and decreasing the time to reach biological stabilization by 70–77%. Due to the transition of operation to a geothermal system at the end of heat production lifetime of landfills, heat extraction systems provide long-term sustainable alternative energy sources with appreciable energy production in comparison to other renewable technologies. DA - 2018/1// PY - 2018/1// DO - 10.1016/j.wasman.2017.05.050 VL - 71 SP - 244-245 SN - 0956-053X ER - TY - JOUR TI - Accessing an Expanded Exposure Science Module at the Comparative Toxicogenomics Database AU - Grondin, Cynthia J. AU - Davis, Allan Peter AU - Wiegers, Thomas C. AU - Wiegers, Jolene A. AU - Mattingly, Carolyn J. T2 - ENVIRONMENTAL HEALTH PERSPECTIVES AB - Summary: The Comparative Toxicogenomics Database (CTD; http://ctdbase.org) is a free resource that provides manually curated information on chemical, gene, phenotype, and disease relationships to advance understanding of the effect of environmental exposures on human health. Four core content areas are independently curated: chemical–gene interactions, chemical–disease and gene–disease associations, chemical–phenotype interactions, and environmental exposure data (e.g., effects of chemical stressors on humans). Since releasing exposure data in 2015, we have vastly increased our coverage of chemicals and disease/phenotype outcomes; greatly expanded access to exposure content; added search capability by stressors, cohorts, population demographics, and measured outcomes; and created user-specified displays of content. These enhancements aim to facilitate human studies by allowing comparisons among experimental parameters and across studies involving specified chemicals, populations, or outcomes. Integration of data among CTD’s four content areas and external data sets, such as Gene Ontology annotations and pathway information, links exposure data with over 1.8 million chemical–gene, chemical–disease and gene–disease interactions. Our analysis tools reveal direct and inferred relationships among the data and provide opportunities to generate predictive connections between environmental exposures and population-level health outcomes. https://doi.org/10.1289/EHP2873 DA - 2018/1// PY - 2018/1// DO - 10.1289/ehp2873 VL - 126 IS - 1 SP - SN - 1552-9924 ER -