TY - CHAP TI - Alterations in skeletogenesis during medaka embryonic development AU - Kullman, S.W. AU - Watson, A.D. T2 - Medaka: Biology, Management, and Experimental Protocols A2 - Murata, K. A2 - Kinoshita, M. A2 - Naruse, K. A2 - Tanaka, M. A2 - Kamei, Y. PY - 2019/// ET - 2nd PB - Wiley SN - 9781119575290 9781119575399 ER - TY - SOUND TI - Solving the Plastic Waste Problem AU - Barlaz, M.A. DA - 2019/// PY - 2019/// ER - TY - CONF TI - Per- and Polyfluoroalkyl Substances (PFAS) in Landfill Leachate and Municipal Wastewater and Occurrence in Drinking Water Sources AU - Thelusmond, J.R. AU - Barlaz, M.A. T2 - SETAC C2 - 2019/// CY - Toronto, Canada DA - 2019/// PY - 2019/11/4/ ER - TY - CONF TI - PFAS in Landfill Leachate and Municipal Wastewater AU - Barlaz, M.A. AU - Thelusmond, J.-R. T2 - Environmental Research & Education Foundation (EREF) Summit on PFAS in Leachate C2 - 2019/// CY - Ypsilanti, MI DA - 2019/// PY - 2019/8/14/ ER - TY - CONF TI - Linking Anaerobic Microbial Population Dynamics to Waste Type and Decomposition Stage AU - Barlaz, M.A. AU - Reyes, F.L. AU - Wang, L. AU - Lee, E. T2 - Environmental Research and Education Foundation (EREF) Summit on Municipal Solid Waste (MSW) Organics C2 - 2019/// CY - Burlingame, CA DA - 2019/// PY - 2019/7/17/ ER - TY - CONF TI - The presence of poly- and perfluoroalkyl substances (PFAS) in landfill leachate AU - Barlaz, M.A. T2 - Solid Waste Association of North America, North Carolina Chapter (NC SWANA) Spring Conference C2 - 2019/// CY - Wrightsville Beach, NC DA - 2019/// PY - 2019/3/5/ ER - TY - JOUR TI - Cadmium exposure and MEG3 methylation differences between Whites and African Americans in the NEST Cohort AU - House, John S AU - Hall, Jonathan AU - Park, Sarah S AU - Planchart, Antonio AU - Money, Eric AU - Maguire, Rachel L AU - Huang, Zhiqing AU - Mattingly, Carolyn J AU - Skaar, David AU - Tzeng, Jung Ying AU - Darrah, Thomas H AU - Vengosh, Avner AU - Murphy, Susan K AU - Jirtle, Randy L AU - Hoyo, Cathrine T2 - Environmental Epigenetics AB - Cadmium (Cd) is a ubiquitous environmental pollutant associated with a wide range of health outcomes including cancer. However, obscure exposure sources often hinder prevention efforts. Further, although epigenetic mechanisms are suspected to link these associations, gene sequence regions targeted by Cd are unclear. Aberrant methylation of a differentially methylated region (DMR) on the MEG3 gene that regulates the expression of a cluster of genes including MEG3, DLK1, MEG8, MEG9 and DIO3 has been associated with multiple cancers. In 287 infant-mother pairs, we used a combination of linear regression and the Getis-Ord Gi* statistic to determine if maternal blood Cd concentrations were associated with offspring CpG methylation of the sequence region regulating a cluster of imprinted genes including MEG3. Correlations were used to examine potential sources and routes. We observed a significant geographic co-clustering of elevated prenatal Cd levels and MEG3 DMR hypermethylation in cord blood (P = 0.01), and these findings were substantiated in our statistical models (β = 1.70, se = 0.80, P = 0.03). These associations were strongest in those born to African American women (β = 3.52, se = 1.32, P = 0.01) compared with those born to White women (β = 1.24, se = 2.11, P = 0.56) or Hispanic women (β = 1.18, se = 1.24, P = 0.34). Consistent with Cd bioaccumulation during the life course, blood Cd levels increased with age (β = 0.015 µg/dl/year, P = 0.003), and Cd concentrations were significantly correlated between blood and urine (ρ > 0.47, P < 0.01), but not hand wipe, soil or house dust concentrations (P > 0.05). Together, these data support that prenatal Cd exposure is associated with aberrant methylation of the imprint regulatory element for the MEG3 gene cluster at birth. However, neither house-dust nor water are likely exposure sources, and ingestion via contaminated hands is also unlikely to be a significant exposure route in this population. Larger studies are required to identify routes and sources of exposure. DA - 2019/7/1/ PY - 2019/7/1/ DO - 10.1093/eep/dvz014 VL - 5 IS - 3 LA - en OP - SN - 2058-5888 UR - http://dx.doi.org/10.1093/eep/dvz014 DB - Crossref KW - maternal exposures KW - imprinted genes KW - offspring epigenetics KW - cadmium KW - CpG methylation KW - racial epigenetic outcome differences ER - TY - CHAP TI - Systems and Methods for Studying Microbial Processes and Communities in Landfills AU - Weaver, Joseph E. AU - Wang, Ling AU - de los Reyes, Francis L., III AU - Barlaz, Morton A. T2 - Advances in Environmental Microbiology PY - 2019/// DO - 10.1007/978-3-030-10777-2_5 SP - 129-150 OP - PB - Springer International Publishing SN - 9783030107758 9783030107772 UR - http://dx.doi.org/10.1007/978-3-030-10777-2_5 DB - Crossref ER - TY - JOUR TI - CLARITY-BPA academic laboratory studies identify consistent low-dose Bisphenol A effects on multiple organ systems AU - Prins, G.S. AU - Patisaul, H.B. AU - Belcher, S.M. AU - Vandenberg, L.N. T2 - Basic and Clinical Pharmacology and Toxicology AB - Bisphenol A (BPA) is a high-production chemical used in a variety of applications worldwide. While BPA has been documented as an endocrine-disrupting chemical (EDC) having adverse health-related outcomes in multiple studies, risk assessment for BPA has lagged due to reliance on guideline toxicology studies over academic ones with end-points considered more sensitive and appropriate. To address current controversies on BPA safety, the United States National Institute of Environmental Health Sciences (NIEHS), the National Toxicology Program (NTP) and the Food and Drug Administration (FDA) established the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) using the NCTR Sprague-Dawley rats. The goal of CLARITY-BPA is to perform a traditional regulatory toxicology study (Core study) in conjunction with multiple behavioural, molecular and cellular studies by academic laboratories focused on previously identified BPA-sensitive organ systems (Academic studies). Combined analysis of the data from both study types will be undertaken by the NTP with the aim of resolving uncertainties on BPA toxicity. To date, the Core study has been completed and a draft report released. Most of the academic studies have also been finalized and published in peer-reviewed journals. In light of this important milestone, the PPTOX-VI meeting held in the Faroe Islands, 27-30 May 2018 devoted a plenary session to CLARITY-BPA with presentations by multiple investigators with the purpose of highlighting key outcome. This MiniReview synthesizes the results of three academic studies presented at this plenary session, evaluates recently published findings by other CLARITY-BPA academic studies to provide an early combined overview of this emerging data and places this in the context of the Core study findings. This co-ordinated effort revealed a plethora of significant BPA effects across multiple organ systems and BPA doses with non-monotonic responses across the dose range utilized. Remarkably consistent across most studies, including the Core study, are low-dose effects (2.5, 25 and 250 μg BPA/kg body-weight). Collectively, the findings highlighted herein corroborate a significant body of evidence that documents adverse effects of BPA at doses relevant to human exposures and emphasizes the need for updated risk assessment analysis. DA - 2019/// PY - 2019/// DO - 10.1111/bcpt.13125 VL - 125 IS - S3 SP - 14-31 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85055169145&partnerID=MN8TOARS KW - Bisphenol A KW - CLARITY-BPA KW - endocrine disruptor KW - endocrine-disrupting chemical KW - oestrogen ER - TY - JOUR TI - Artemisinin Biosynthesis in Non-glandular Trichome Cells of Artemisia annua AU - Judd, Rika AU - Bagley, M. Caleb AU - Li, Mingzhuo AU - Zhu, Yue AU - Lei, Caiyan AU - Yuzuak, Seyit AU - Ekelöf, Måns AU - Pu, Gaobin AU - Zhao, Xiting AU - Muddiman, David C. AU - Xie, De-Yu T2 - Molecular Plant AB - Artemisinin-based combination therapy (ACT) forms the first line of malaria treatment. However, the yield fluctuation of artemisinin has remained an unsolved problem in meeting the global demand for ACT. This problem is mainly caused by the glandular trichome (GT)-specific biosynthesis of artemisinin in all currently used Artemisia annua cultivars. Here, we report that non-GT cells of self-pollinated inbred A. annua plants can express the artemisinin biosynthetic pathway. Gene expression analysis demonstrated the transcription of six known pathway genes in GT-free leaves and calli of inbred A. annua plants. LC–qTOF–MS/MS analysis showed that these two types of GT-free materials produce artemisinin, artemisinic acid, and arteannuin B. Detailed IR-MALDESI image profiling revealed that these three metabolites and dihydroartemisinin are localized in non-GT cells of leaves of inbred A. annua plants. Moreover, we employed all the above approaches to examine artemisinin biosynthesis in the reported A. annua glandless (gl) mutant. The resulting data demonstrated that leaves of regenerated gl plantlets biosynthesize artemisinin. Collectively, these findings not only add new knowledge leading to a revision of the current dogma of artemisinin biosynthesis in A. annua but also may expedite innovation of novel metabolic engineering approaches for high and stable production of artemisinin in the future. DA - 2019/5// PY - 2019/5// DO - 10.1016/j.molp.2019.02.011 VL - 12 IS - 5 SP - 704-714 J2 - Molecular Plant LA - en OP - SN - 1674-2052 UR - http://dx.doi.org/10.1016/j.molp.2019.02.011 DB - Crossref KW - Artemisia annua KW - artemisinin KW - glandular trichome KW - non-glandular trichome cell ER - TY - JOUR TI - Investigating host-pathogen meta-metabolic interactions of Magnaporthe oryzae infected barley using infrared matrix-assisted laser desorption electrospray ionization mass spectrometry AU - Kalmar, Jaclyn Gowen AU - Oh, Yeonyee AU - Dean, Ralph A. AU - Muddiman, David T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY DA - 2019/// PY - 2019/// DO - 10.1007/s00216-019-02216-z KW - IR-MALDESI KW - Mass spectrometry imaging KW - Orbitrap KW - Magnaporthe oryzae KW - Image recognition KW - Polarity switching ER - TY - JOUR TI - Corrections to “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 - Van Den Driessche, George A. AU - Valery, Alain R. B. AU - Fourches, Denis AU - Freeman, Harold S. T2 - ACS Sustainable Chemistry & Engineering AB - ADVERTISEMENT RETURN TO ISSUEPREVCorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrections to “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”Tova N. Williams*Tova N. WilliamsMore by Tova N. Williamshttp://orcid.org/0000-0003-4284-3068, George A. Van Den DriesscheGeorge A. Van Den DriesscheMore by George A. Van Den Driessche, Alain R. B. ValeryAlain R. B. ValeryMore by Alain R. B. Valery, Denis Fourches*Denis FourchesMore by Denis Fourcheshttp://orcid.org/0000-0001-5642-8303, and Harold S. Freeman*Harold S. FreemanMore by Harold S. FreemanCite this: ACS Sustainable Chem. Eng. 2019, 7, 1, 1806Publication Date (Web):December 4, 2018Publication History Received27 October 2018Published online4 December 2018Published inissue 7 January 2019https://doi.org/10.1021/acssuschemeng.8b05545Copyright © 2018 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views542Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. 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Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (259 KB) Get e-AlertsSUBJECTS:Biological databases,Chemoinformatics,Dyes and pigments,Rational design Get e-Alerts DA - 2019/1/7/ PY - 2019/1/7/ DO - 10.1021/ACSSUSCHEMENG.8B05545 VL - 7 IS - 1 SP - 1806–1806 SN - 2168-0485 2168-0485 UR - http://dx.doi.org/10.1021/ACSSUSCHEMENG.8B05545 ER - TY - JOUR TI - NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods AU - De Leoz, Maria Lorna A. AU - Duewer, David L. AU - Fung, Adam AU - Liu, Lily AU - Yau, Hoi Kei AU - Potter, Oscar AU - Staples, Gregory O. AU - Furuki, Kenichiro AU - Frenkel, Ruth AU - Hu, Yunli AU - Sosic, Zoran AU - Zhang, Peiqing AU - Altmann, Friedrich AU - Gru«nwald-Grube, Clemens AU - Shao, Chun AU - Zaia, Joseph AU - Evers, Waltraud AU - Pengelley, Stuart AU - Suckau, Detlev AU - Wiechmann, Anja AU - Resemann, Anja AU - Jabs, Wolfgang AU - Beck, Alain AU - Froehlich, John W. AU - Huang, Chuncui AU - Li, Yan AU - Liu, Yaming AU - Sun, Shiwei AU - Wang, Yaojun AU - Seo, Youngsuk AU - An, Hyun Joo AU - Reichardt, Niels-Christian AU - Ruiz, Juan Echevarria AU - Archer-Hartmann, Stephanie AU - Azadi, Parastoo AU - Bell, Len AU - Lakos, Zsuzsanna AU - An, Yanming AU - Cipollo, John F. AU - Pucic-Bakovic, Maja AU - Štambuk, Jerko AU - Lauc, Gordan AU - Li, Xu AU - Wang, Peng George AU - Bock, Andreas AU - Hennig, René AU - Rapp, Erdmann AU - Creskey, Marybeth AU - Cyr, Terry D. AU - Nakano, Miyako AU - Sugiyama, Taiki AU - Leung, Pui-King Amy AU - Link-Lenczowski, Paweł AU - Jaworek, Jolanta AU - Yang, Shuang AU - Zhang, Hui AU - Kelly, Tim AU - Klapoetke, Song AU - Cao, Rui AU - Kim, Jin Young AU - Lee, Hyun Kyoung AU - Lee, Ju Yeon AU - Yoo, Jong Shin AU - Kim, Sa-Rang AU - Suh, Soo-Kyung AU - de Haan, Noortje AU - Falck, David AU - Lageveen-Kammeijer, Guinevere S. M. AU - Wuhrer, Manfred AU - Emery, Robert J. AU - Kozak, Radoslaw P. AU - Liew, Li Phing AU - Royle, Louise AU - Urbanowicz, Paulina A. AU - Packer, Nicolle H. AU - Song, Xiaomin AU - Everest-Dass, Arun AU - Lattová, Erika AU - Cajic, Samanta AU - Alagesan, Kathirvel AU - Kolarich, Daniel AU - Kasali, Toyin AU - Lindo, Viv AU - Chen, Yuetian AU - Goswami, Kudrat AU - Gau, Brian AU - Amunugama, Ravi AU - Jones, Richard AU - Stroop, Corné J. M. AU - Kato, Koichi AU - Yagi, Hirokazu AU - Kondo, Sachiko AU - Yuen, C. T. AU - Harazono, Akira AU - Shi, Xiaofeng AU - Magnelli, Paula E. AU - Kasper, Brian T. AU - Mahal, Lara AU - Harvey, David J. AU - O'Flaherty, Roisin AU - Rudd, Pauline M. AU - Saldova, Radka AU - Hecht, Elizabeth S. AU - Muddiman, David C. AU - Kang, Jichao AU - Bhoskar, Prachi AU - Menard, Daniele AU - Saati, Andrew AU - Merle, Christine AU - Mast, Steven AU - Tep, Sam AU - Truong, Jennie AU - Nishikaze, Takashi AU - Sekiya, Sadanori AU - Shafer, Aaron AU - Funaoka, Sohei AU - Toyoda, Masaaki AU - de Vreugd, Peter AU - Caron, Cassie AU - Pradhan, Pralima AU - Tan, Niclas Chiang AU - Mechref, Yehia AU - Patil, Sachin AU - Rohrer, Jeffrey S. AU - Chakrabarti, Ranjan AU - Dadke, Disha AU - Lahori, Mohammedazam AU - Zou, Chunxia AU - Cairo, Christopher AU - Reiz, Béla AU - Whittal, Randy M. AU - Lebrilla, Carlito B. AU - Wu, Lauren AU - Guttman, Andras AU - Szigeti, Marton AU - Kremkow, Benjamin G. AU - Lee, Kelvin H. AU - Sihlbom, Carina AU - Adamczyk, Barbara AU - Jin, Chunsheng AU - Karlsson, Niclas G. AU - Örnros, Jessica AU - Larson, Göran AU - Nilsson, Jonas AU - Meyer, Bernd AU - Wiegandt, Alena AU - Komatsu, Emy AU - Perreault, Helene AU - Bodnar, Edward D. AU - Said, Nassur AU - Francois, Yannis-Nicolas AU - Leize-Wagner, Emmanuelle AU - Maier, Sandra AU - Zeck, Anne AU - Heck, Albert J. R. AU - Yang, Yang AU - Haselberg, Rob AU - Yu, Ying Qing AU - Alley, William AU - Leone, Joseph W. AU - Yuan, Hua AU - Stein, Stephen E. T2 - Molecular & Cellular Proteomics AB - Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods. Biologics have recently emerged as critically important drugs from health and economic perspectives. Two-thirds of approved biologics are glycoproteins, i.e. proteins containing glycans as post-translational modification. Alteration in glycosylation may impact the safety and efficacy of the drug, including its clearance rates, effector functions, folding, immunogenicity, solubility, and biological activity. In addition to glycomic profiling of new drug candidates, analysis of glycoforms is essential for monitoring production batches of established drugs and comparing biosimilars and biobetters to originator drugs. This report describes results of a broad interlaboratory study designed to determine both the level of variability in current measurement methods as well as to support consensus measurement values for a reference material. Participation was open to all laboratories, regardless of experience or preferred analytical method. Because specific methods selected by participating laboratories varied greatly, as did their degree of expertise, this study was not designed to determine “best” methods, but to provide a “snapshot” of the currently used methods for biologic glycosylation measurement. Unfortunately, this diversity in experience and objective prevented a deeper analysis of the variability of results, with some highly experienced labs using well-developed standard operating procedures, and with others using novel approaches or exploiting their unique capabilities. The study rationale and design are presented in detail in supplementary Discussion S1. Glycosylation analysis is inherently challenging because, unlike amino acids in proteins which are encoded by the genome, sequential addition of monosaccharide residues is not template-driven. It is rather dictated by competing enzymatic activities, leading to heterogeneity. Even at the same site of glycosylation, diverse glycans with different linkages, number of antenna, and monosaccharide compositions are possible, giving rise to challenges in separation (chromatography) and isomerization (mass spectrometry). A common glycosylation in mAbs is N-glycosylation where the glycans are linked to the nitrogen of the Asn residue of the protein with a consensus sequence Asn-X-Ser/Thr or, more rarely, Asn-X-Cys where X is any amino acid except proline. Moreover, N-glycans have a common five-membered trimannosyl chitobiose core, Manα1–6(Manα1–3)Manβ1- 4GlcNAcβ1–4GlcNAcβ1-Asn-X-Ser/Thr. The highly complex nature of N-glycosylation analysis has given rise to a proliferation of different methods (1Yang S. Li Y. Shah P. Zhang H. Glycomic analysis using glycoprotein immobilization for glycan extraction.Anal. Chem. 2013; 85: 5555-5561Crossref PubMed Scopus (49) Google Scholar, 2Vreeker G.C.M. Wuhrer M. Reversed-phase separation methods for glycan analysis.Anal. Bioanal. Chem. 2017; 409: 359-378Crossref PubMed Scopus (76) Google Scholar, 3Ruhaak L.R. Zauner G. Huhn C. Bruggink C. Deelder A.M. Wuhrer M. Glycan labeling strategies and their use in identification and quantification.Anal. Bioanal. Chem. 2010; 397: 3457-3481Crossref PubMed Scopus (338) Google Scholar, 4Dotz V. Haselberg R. Shubhakar A. Kozak R.P. Falck D. Rombouts Y. Reusch D. Somsen G.W. Fernandes D.L. Wuhrer M. Mass spectrometry for glycosylation analysis of biopharmaceuticals.Trac-Trend Anal. Chem. 2015; 73: 1-9Crossref Scopus (57) Google Scholar, 5O'Flaherty R. Muniyappa M. Walsh I. Stockmann H. Hutson R. Saldova R. Rudd P.M. High-throughput sequential glycoprofiling of six abundant glycoproteins IgG, IgA, IgM, transferrin, haptoglobin and alpha-1-antitrypsin in ovarian cancer.Glycobiology. 2016; 26: 1430-1431Google Scholar, 6Beck A. Wagner-Rousset E. Ayoub D. Van Dorsselaer A. Sanglier-Cianferani S. Characterization of therapeutic antibodies and related products.Anal. Chem. 2013; 85: 715-736Crossref PubMed Scopus (447) Google Scholar, 7Beck A. Wagner-Rousset E. Bussat M.C. Lokteff M. Klinguer-Hamour C. Haeuw J.F. Goetsch L. Wurch T. Van Dorsselaer A. Corvaia N. Trends in glycosylation, glycoanalysis and glycoengineering of therapeutic antibodies and Fc-fusion proteins.Curr. Pharm. Biotechno. 2008; 9: 482-501Crossref PubMed Scopus (197) Google Scholar, 8Hecht E.S. McCord J.P. Muddiman D.C. Definitive screening design optimization of mass spectrometry parameters for sensitive comparison of filter and solid phase extraction purified, INLIGHT plasma N-glycans.Anal. Chem. 2015; 87: 7305-7312Crossref PubMed Scopus (30) Google Scholar, 9Walker S.H. Taylor A.D. Muddiman D.C. Individuality normalization when labeling with isotopic glycan hydrazide tags (INLIGHT): a novel glycan-relative quantification strategy.J. Am. Soc. Mass Spectr. 2013; 24: 1376-1384Crossref PubMed Scopus (38) Google Scholar, 10Hu Y.L. Shihab T. Zhou S.Y. Wooding K. Mechref Y. LC-MS/MS of permethylated N-glycans derived from model and human blood serum glycoproteins.Electrophoresis. 2016; 37: 1498-1505Crossref PubMed Scopus (33) Google Scholar, 11Mechref Y. Muddiman D.C. Recent advances in glycomics, glycoproteomics and allied topics.Anal. Bioanal. Chem. 2017; 409: 355-357Crossref PubMed Scopus (21) Google Scholar, 12Zhou S.Y. Hu Y.L. Veillon L. Snovida S.I. Rogers J.C. Saba J. Mechref Y. Quantitative LC-MS/MS glycomic analysis of biological samples using aminoxyTMT.Anal. Chem. 2016; 88: 7515-7522Crossref PubMed Scopus (51) Google Scholar, 13Yang N. Goonatilleke E. Park D. Song T. Fan G.R. Lebrilla C.B. Quantitation of site-specific glycosylation in manufactured recombinant monoclonal antibody drugs.Anal. Chem. 2016; 88: 7091-7100Crossref PubMed Scopus (24) Google Scholar, 14Hong Q.T. Ruhaak L.R. Stroble C. Parker E. Huang J.C. Maverakis E. Lebrilla C.B. A method for comprehensive glycosite-mapping and direct quantitation of serum glycoproteins.J. Proteome Res. 2015; 14: 5179-5192Crossref PubMed Scopus (61) Google Scholar). Currently, N-glycosylation is examined at the level of intact proteins, protein fragments, peptides, glycans, or monosaccharides. Analytes are then analyzed by mass spectrometry (MS) 1The abbreviations used are:MSgeneric mass spectrometry or first stage mass spectrometryAAaminobenzoic acidABaminobenzamideAPTS9-aminopyrene-1,4–6-trisulfonateC4C4 (butyl) desalting columnC8C8 (octyl) desalting columnCEcapillary electrophoresisCFGConsortium for Functional GlycomicsDIdirect infusionExoexoglycosidaseFabantigen-binding fragment of a monoclonal antibodyFccrystallizable fragment of a monoclonal antibodyFDfluorescence detectionGUglucose unitsHILIChydrophilic interaction liquid chromatographyHPAEC-PADhigh performance anion exchange chromatography with pulsed amperometric detectionICion chromatographyIdeSimmunoglobulin G-degrading enzymeLCliquid chromatographyLIFlaser-induced fluorescence detectionLoRlimit of reportingmAbmonoclonal antibodyMALDImatrix-assisted laser desorption/ionizationMRVminimum reported valueMS/MStandem mass spectrometryMSnnth stage MSMTmigration timeNDnot detectedNISTIRNIST internal reportNMRnuclear magnetic resonanceNQnot quantifiedPApeak area/integrationPGCporous graphitized carbonPHpeak heightPNGase FPeptide-N-Glycosidase FPSprimary sampleRPreversed-phaseRTretention timeSECsize-exclusion chromatographyUOXFOxford Glycobiology InstitutexCGEmultiplexed capillary gel electrophoresis. 1The abbreviations used are:MSgeneric mass spectrometry or first stage mass spectrometryAAaminobenzoic acidABaminobenzamideAPTS9-aminopyrene-1,4–6-trisulfonateC4C4 (butyl) desalting columnC8C8 (octyl) desalting columnCEcapillary electrophoresisCFGConsortium for Functional GlycomicsDIdirect infusionExoexoglycosidaseFabantigen-binding fragment of a monoclonal antibodyFccrystallizable fragment of a monoclonal antibodyFDfluorescence detectionGUglucose unitsHILIChydrophilic interaction liquid chromatographyHPAEC-PADhigh performance anion exchange chromatography with pulsed amperometric detectionICion chromatographyIdeSimmunoglobulin G-degrading enzymeLCliquid chromatographyLIFlaser-induced fluorescence detectionLoRlimit of reportingmAbmonoclonal antibodyMALDImatrix-assisted laser desorption/ionizationMRVminimum reported valueMS/MStandem mass spectrometryMSnnth stage MSMTmigration timeNDnot detectedNISTIRNIST internal reportNMRnuclear magnetic resonanceNQnot quantifiedPApeak area/integrationPGCporous graphitized carbonPHpeak heightPNGase FPeptide-N-Glycosidase FPSprimary sampleRPreversed-phaseRTretention timeSECsize-exclusion chromatographyUOXFOxford Glycobiology InstitutexCGEmultiplexed capillary gel electrophoresis. (1Yang S. Li Y. Shah P. Zhang H. Glycomic analysis using glycoprotein immobilization for glycan extraction.Anal. Chem. 2013; 85: 5555-5561Crossref PubMed Scopus (49) Google Scholar); liquid chromatography (LC) with fluorescence detection (FD)(2Vreeker G.C.M. Wuhrer M. Reversed-phase separation methods for glycan analysis.Anal. Bioanal. Chem. 2017; 409: 359-378Crossref PubMed Scopus (76) Google Scholar) and/or MS detection; capillary electrophoresis (CE) with MS detection (3Ruhaak L.R. Zauner G. Huhn C. Bruggink C. Deelder A.M. Wuhrer M. Glycan labeling strategies and their use in identification and quantification.Anal. Bioanal. Chem. 2010; 397: 3457-3481Crossref PubMed Scopus (338) Google Scholar); CE-laser-induced fluorescence detection (CE-LIF); high performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD); nuclear magnetic resonance (NMR) spectroscopy; or a combination of these techniques (4Dotz V. Haselberg R. Shubhakar A. Kozak R.P. Falck D. Rombouts Y. Reusch D. Somsen G.W. Fernandes D.L. Wuhrer M. Mass spectrometry for glycosylation analysis of biopharmaceuticals.Trac-Trend Anal. Chem. 2015; 73: 1-9Crossref Scopus (57) Google Scholar). generic mass spectrometry or first stage mass spectrometry aminobenzoic acid aminobenzamide 9-aminopyrene-1,4–6-trisulfonate C4 (butyl) desalting column C8 (octyl) desalting column capillary electrophoresis Consortium for Functional Glycomics direct infusion exoglycosidase antigen-binding fragment of a monoclonal antibody crystallizable fragment of a monoclonal antibody fluorescence detection glucose units hydrophilic interaction liquid chromatography high performance anion exchange chromatography with pulsed amperometric detection ion chromatography immunoglobulin G-degrading enzyme liquid chromatography laser-induced fluorescence detection limit of reporting monoclonal antibody matrix-assisted laser desorption/ionization minimum reported value tandem mass spectrometry nth stage MS migration time not detected NIST internal report nuclear magnetic resonance not quantified peak area/integration porous graphitized carbon peak height Peptide-N-Glycosidase F primary sample reversed-phase retention time size-exclusion chromatography Oxford Glycobiology Institute multiplexed capillary gel electrophoresis. generic mass spectrometry or first stage mass spectrometry aminobenzoic acid aminobenzamide 9-aminopyrene-1,4–6-trisulfonate C4 (butyl) desalting column C8 (octyl) desalting column capillary electrophoresis Consortium for Functional Glycomics direct infusion exoglycosidase antigen-binding fragment of a monoclonal antibody crystallizable fragment of a monoclonal antibody fluorescence detection glucose units hydrophilic interaction liquid chromatography high performance anion exchange chromatography with pulsed amperometric detection ion chromatography immunoglobulin G-degrading enzyme liquid chromatography laser-induced fluorescence detection limit of reporting monoclonal antibody matrix-assisted laser desorption/ionization minimum reported value tandem mass spectrometry nth stage MS migration time not detected NIST internal report nuclear magnetic resonance not quantified peak area/integration porous graphitized carbon peak height Peptide-N-Glycosidase F primary sample reversed-phase retention time size-exclusion chromatography Oxford Glycobiology Institute multiplexed capillary gel electrophoresis. One popular approach is the release of glycans where N-glycans are cleaved from proteins using Peptide-N-Glycosidase F (PNGase F), which hydrolyzes the side-chain amide group of the glycosylated asparagine. Before analysis, glycans may be subjected to permethylation, reduction, or fluorophore labeling to increase sensitivity and specificity. Structure elucidation and isomer separation is possible using the glycan-release approach, but it lacks information on the site of glycosylation because analysis is performed after the glycans are cleaved from the protein. Analysis of glycopeptides can provide glycosylation site information along with glycan compositions. In this approach, mAbs are digested with proteases such as trypsin (and less commonly used enzymes such as chymotrypsin, LysC, LysN, AspN, GluC, or ArgC) to produce peptides and glycopeptides that are then typically analyzed using MALDI-MS and LC-MS(/MS) methods (and less commonly CE-MS(/MS) methods (15Giorgetti J. D'Atri V. Canonge J. Lechner A. Guillarme D. Colas O. Wagner-Rousset E. Beck A. Leize-Wagner E. Francois Y.N. Monoclonal antibody N-glycosylation profiling using capillary electrophoresis - Mass spectrometry: Assessment and method validation.Talanta. 2018; 178: 530-537Crossref PubMed Scopus (45) Google Scholar)). The peptide attached to the glycoform gives information on the site of glycosylation. Potential disadvantages include challenges in differentiating isomers and suppression of glycopeptide ions because of peptide ions at the precursor (MS1) level. The latter could be alleviated by (two-dimensional) LC or enrichment methods (16Dong Q. Yan X. Liang Y. Stein S.E. In-depth characterization and spectral library building of glycopeptides in the tryptic digest of a monoclonal antibody using 1D and 2D LC-MS/MS.J. Proteome Res. 2016; 15: 1472-1486Crossref PubMed Scopus (28) Google Scholar). Middle-down and top-down approaches characterize the glycosylation by analyzing protein fragments and intact proteins, respectively. In the middle-down approach, mAbs are treated with immunoglobulin G-degrading enzyme (IdeS), an endopeptidase that cleaves heavy chains below the hinge region, resulting in antigen-binding (Fab) and crystallizable (Fc) fragments. These large fragments are then usually analyzed by MS. Protein fragments have a lower molecular mass than the intact protein and could be better resolved in MS compared with the analysis of intact mAbs in the top-down approach. Compared with other techniques, the top-down approach provides the advantage that little-to-no sample preparation steps are needed before the analysis. Typically, only desalting of the intact mAb is necessary, which is normally performed with a desalting column (e.g. C4, C8) followed by the analysis with MS. However, because top-down and middle-down analyses often result in higher masses, fewer glycan compositions can be distinguished because of lack of resolution compared with other MS-based methods. The diversity of these methods presents a major challenge in the interpretation of N-glycosylation measurements. Unfortunately, only a few multi-laboratory studies have been reported assessing the performance of the different approaches (17Wada Y. Azadi P. Costello C.E. Dell A. Dwek R.A. Geyer H. Geyer R. Kakehi K. Karlsson N.G. Kato K. Kawasaki N. Khoo K.H. Kim S. Kondo A. Lattova E. Mechref Y. Miyoshi E. Nakamura K. Narimatsu H. Novotny M.V. Packer N.H. Perreault H. Peter-Katalinic J. Pohlentz G. Reinhold V.N. Rudd P.M. Suzuki A. Taniguchi N. Comparison of the methods for profiling glycoprotein glycans–HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study.Glycobiology. 2007; 17: 411-422Crossref PubMed Scopus (350) Google Scholar, 18Wada Y. Dell A. Haslam S.M. Tissot B. Canis K. Azadi P. Backstrom M. Costello C.E. Hansson G.C. Hiki Y. Ishihara M. Ito H. Kakehi K. Karlsson N. Hayes C.E. Kato K. Kawasaki N. Khoo K.H. Kobayashi K. Kolarich D. Kondo A. Lebrilla C. Nakano M. Narimatsu H. Novak J. Novotny M.V. Ohno E. Packer N.H. Palaima E. Renfrow M.B. Tajiri M. Thomsson K.A. Yagi H. Yu S.Y. Taniguchi N. Comparison of methods for profiling O-glycosylation: Human Proteome Organisation Human Disease Glycomics/Proteome Initiative multi-institutional study of IgA1.Mol. Cell. Proteomics. 2010; 9: 719-727Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 19Thobhani S. Yuen C.T. Bailey M.J. Jones C. Identification and quantification of N-linked oligosaccharides released from glycoproteins: an inter-laboratory study.Glycobiology. 2009; 19: 201-211Crossref PubMed Scopus (35) Google Scholar, 20Leymarie N. Griffin P.J. Jonscher K. Kolarich D. Orlando R. McComb M. Zaia J. Aguilan J. Alley W.R. Altmann F. Ball L.E. Basumallick L. Bazemore-Walker C.R. Behnken H. Blank M.A. Brown K.J. Bunz S.C. Cairo C.W. Cipollo J.F. Daneshfar R. Desaire H. Drake R.R. Go E.P. Goldman R. Gruber C. Halim A. Hathout Y. Hensbergen P.J. Horn D.M. Hurum D. Jabs W. Larson G. Ly M. Mann B.F. Marx K. Mechref Y. Meyer B. Möginger U. Neusüâ C. Nilsson J. Novotny M.V. Nyalwidhe J.O. Packer N.H. Pompach P. Reiz B. Resemann A. Rohrer J.S. Ruthenbeck A. Sanda M. Schulz J.M. Schweiger-Hufnagel U. Sihlbom C. Song E. Staples G.O. Suckau D. Tang H. Thaysen-Andersen M. Viner R.I. An Y. Valmu L. Wada Y. Watson M. Windwarder M. Whittal R. Wuhrer M. Zhu Y. Zou C. Interlaboratory study on differential analysis of protein glycosylation by mass spectrometry: The ABRF Glycoprotein Research Multi-Institutional Study 2012.Mol. Cell. Proteomics. 2013; 12: 2935-2951Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar, 21Reusch D. Haberger M. Maier B. Maier M. Kloseck R. Zimmermann B. Hook M. Szabo Z. Tep S. Wegstein J. Alt N. Bulau P. Wuhrer M. Comparison of methods for the analysis of therapeutic immunoglobulin G Fc-glycosylation profiles-Part 1: Separation-based methods.Mabs. 2015; 7: 167-179Crossref PubMed Scopus (127) Google Scholar). In two studies by the Human Proteome Organization (HUPO), relative abundances of N-glycans (in transferrin and IgG) (17Wada Y. Azadi P. Costello C.E. Dell A. Dwek R.A. Geyer H. Geyer R. Kakehi K. Karlsson N.G. Kato K. Kawasaki N. Khoo K.H. Kim S. Kondo A. Lattova E. Mechref Y. Miyoshi E. Nakamura K. Narimatsu H. Novotny M.V. Packer N.H. Perreault H. Peter-Katalinic J. Pohlentz G. Reinhold V.N. Rudd P.M. Suzuki A. Taniguchi N. Comparison of the methods for profiling glycoprotein glycans–HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study.Glycobiology. 2007; 17: 411-422Crossref PubMed Scopus (350) Google Scholar) and O-glycans (in IgA1) (18Wada Y. Dell A. Haslam S.M. Tissot B. Canis K. Azadi P. Backstrom M. Costello C.E. Hansson G.C. Hiki Y. Ishihara M. Ito H. Kakehi K. Karlsson N. Hayes C.E. Kato K. Kawasaki N. Khoo K.H. Kobayashi K. Kolarich D. Kondo A. Lebrilla C. Nakano M. Narimatsu H. Novak J. Novotny M.V. Ohno E. Packer N.H. Palaima E. Renfrow M.B. Tajiri M. Thomsson K.A. Yagi H. Yu S.Y. Taniguchi N. Comparison of methods for profiling O-glycosylation: Human Proteome Organisation Human Disease Glycomics/Proteome Initiative multi-institutional study of IgA1.Mol. Cell. Proteomics. 2010; 9: 719-727Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar) were analyzed by 20 and 15 laboratories, respectively. They observed that MS-based methods are efficient in identifying and quantifying glycans. However, there were no participants from biopharmaceutical companies. Here we present the design and results of our interlaboratory study of two materials: primary sample (PS) 8670, commonly referred to as NISTmAb (22Formolo T. Ly M. Levy M. Kilpatrick L. Lute S. Phinney K. Marzilli L. Brorson K. Boyne M. Davis D. Schiel J. Determination of the NISTmAb Primary Structure.in: Schiel John E. Davis Darryl L. Borisov Oleg V. State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 2. Biopharmaceutical Characterization: The NISTmAb Case Study. American Chemical Society, 2015: 1-62Crossref Google Scholar), and mod-NISTmAb, a material derived from PS 8670 by modification with galactosidase. PS 8670 is the in-house standard for NIST Reference Material 8671 (23Schiel J.E. Turner A. The NISTmAb Reference Material 8671 lifecycle management and quality plan.Anal. Bioanal. Chem. 2018; 410: 2067-2078Crossref PubMed Scopus (26) Google Scholar). The rationale for the use of these samples is presented in supplementary Discussion S2. This report is based on 103 reports submitted by 76 laboratories worldwide. It builds on the NIST internal report (NISTIR) 8186 (24De Leoz M.L.A. Duewer D.L. Stein S.E. NIST Interlaboratory Study on the Glycosylation of NISTmAb, a Monoclonal Antibody Reference Material.in: NIST Internal Report (NISTIR). 20178186Google Scholar). This interlaboratory study had two goals. The first goal was to determine measurement variability in identifying and quantifying N-glycosylation in monoclonal antibodies across laboratories in the glycomics and glycoproteomics community, including laboratories form biopharmaceutical companies and universities. The second goal was to aid in determining community-based consensus medians for the glycosylation of the PS. The community's consensus values for NISTmAb PS 8670 glycosylation, robustly estimated as medians, represent an unparalleled diversity of approaches applied to the same material and serve as a seminal baseline for comparing glycoanalytical strategies. Finally, we note two quite different levels of identification - by composition and by structure. Compositions are determined by high mass accuracy mass spectrometry, whereas confident isomer identification often requires reference materials or chromatographic retention matching. Two materials were used in the study, (1 the Primary sample (PS) for NIST Reference Material 8671, NISTmAb, Humanized IgG1κ Monoclonal Antibody produced in NS0 cells, and (2 a material derived from the PS by treatment with galactosidase, termed “mod-NISTmAb.” NISTmAb was obtained as a bulk substance prepared using mammalian cell culture and downstream processing. It has one N-glycosylation site at the Fc region of the antibody. mod-NISTmAb was prepared by subjecting a portion of NISTmAb to β-1,4-galactosidase (New England Biolabs, Ipswich, MA) and then adding the resulting solution back to the original NISTmAb (30:70 by mass). The study was conducted in two stages: Stage 1 involved nine selected laboratories who volunteered to assist in final study design; Stage 2 was widely advertised and open to all laboratories. Two samples were shipped to laboratories on June 2015 and August-September 2015 for Stage 1 and Stage 2, respectively. Laboratories received three vials consisting of two blinded monoclonal antibody samples and one buffer solution in 1.0 ml screw-top tubes (Matrix™ Thermo Fisher Scientific, #3740) as follows: •Sample A: white label, frozen liquid, 0.4 mg, 100 mg/ml mAb•Sample B: blue label, frozen liquid, 0.4 mg, 100 mg/ml mAb•Buffer: yellow label, frozen liquid, 1 ml, 25 mmol/L l-Histidine, pH 6.0 Laboratories were informed that both samples are humanized IgG1k expressed in murine suspension culture and that the samples are “drug-like substances” not for human use. The buffer solution was provided as a diluent. Participants used their method of choice to determine the glycan content in the two samples. Participants were requested to provide measurement results using NIST-provided data and method reporting templates (24De Leoz M.L.A. Duewer D.L. Stein S.E. NIST Interlaboratory Study on the Glycosylation of NISTmAb, a Monoclonal Antibody Reference Material.in: NIST Internal Report (NISTIR). 20178186Google Scholar) by July 30, 2015 (Stage 1) and November 6, 2015 (Stage 2). Some laboratories submitted more than one report; each report was assigned a confidential laboratory number (and was treated as a separate laboratory). Participants could enter other glycans or methods in the template; no other post-translational modifications, e.g. lysine glycation, could be reported. Data were analyzed as reported, i.e. no normalization, using a variety of robust statistical analysis techniques to assess measurement reproducibility and to characterize glycan distributions. Results were compiled and evaluated for determination of community's consensus medians, within-laboratory precision, and concordance within the laboratories. A technical summary (24De Leoz M.L.A. Duewer D.L. Stein S.E. NIST Interlaboratory Study on the Glycosylation of NISTmAb, a Monoclonal Antibody Reference Material.in: NIST Internal Report (NISTIR). 20178186Google Scholar) of reported and derived values from all laboratories, a table of all identified glycans, and an individualized graphical analysis of their performance for the exercise were sent to the participating laboratories on June 2, 2017. Package shipped to each laboratory consisted of three vials (Sample A, Sample B, and l-Histidine buffer solution) and a welcome packet (24De Leoz M.L.A. Duewer D.L. Stein S.E. NIST Interlaboratory Study on the Glycosylation of NISTmAb, a Monoclonal Antibody Reference Material.in: NIST Internal Report (NISTIR). 20178186Google Scholar). The three vials were stowed in a rolled, self-sealing bubble wrap bag and placed in an insulated box filled with dry ice. The welcome packet consisted of a cover letter; instructions; packing list/shipment receipt confirmation form; and data, method, and comment reporting sheets. These documents were enclosed in a waterproof sleeve and placed at the top of the shipping box, between the cardboard covering and the foam insulation. A soft copy of the welcome packet was emailed to participants as one spreadsheet workbook with multiple worksheets. Participants were requested to return the filled shipment receipt confirmation form as soon as they received the shipped package. Each laboratory was asked to perform glycosylation analysis of the two samples in triplicate using their own method(s), as summarized in Table I. Briefly, glycans were cleaved by incubating mAbs with PNGase F (74 reports), trypsin/PNGase F (1 report), and Pepsin/PNGase A (1 report). Cleaved glycans were derivatized using fluorescent (54 reports) or non-fluorescent (22 reports) methods. Next, glycans were separated with chromatography (CE (5 reports), HILIC (46 reports), IC (1 report), PGC (6 reports), RP (6 reports)) or without chromatography (12 reports), and then identified by various analytical methods.Table IOverview of analytical techniques for mAb glycosylation analysis used in this interlaboratory studyAnalyteDerivatizationAnalytical methodChromatographyIdentificationQuantificationG DA - 2019/10/7/ PY - 2019/10/7/ DO - 10.1074/mcp.RA119.001677 VL - 19 IS - 1 SP - 11-30 J2 - Mol Cell Proteomics LA - en OP - SN - 1535-9476 1535-9484 UR - http://dx.doi.org/10.1074/mcp.RA119.001677 DB - Crossref KW - Glycomics KW - mass spectrometry KW - fluorescence KW - glycosylation KW - glycoproteins KW - glycan KW - glycopeptide KW - interlaboratory study KW - NISTmAb KW - reference antibody ER - TY - JOUR TI - Does Granular Activated Carbon with Chlorination Produce Safer Drinking Water? From Disinfection Byproducts and Total Organic Halogen to Calculated Toxicity AU - Cuthbertson, Amy A. AU - Kimura, Susana Y. AU - Liberatore, Hannah K. AU - Summers, R. Scott AU - Knappe, Detlef R. U. AU - Stanford, Benjamin D. AU - Maness, J. Clark AU - Mulhern, Riley E. AU - Selbes, Meric AU - Richardson, Susan D. T2 - ENVIRONMENTAL SCIENCE & TECHNOLOGY AB - Granular activated carbon (GAC) adsorption is well-established for controlling regulated disinfection byproducts (DBPs), but its effectiveness for unregulated DBPs and DBP-associated toxicity is unclear. In this study, GAC treatment was evaluated at three full-scale chlorination drinking water treatment plants over different GAC service lives for controlling 61 unregulated DBPs, 9 regulated DBPs, and speciated total organic halogen (total organic chlorine, bromine, and iodine). The plants represented a range of impacts, including algal, agricultural, and industrial wastewater. This study represents the most extensive full-scale study of its kind and seeks to address the question of whether GAC can make drinking water safer from a DBP perspective. Overall, GAC was effective for removing DBP precursors and reducing DBP formation and total organic halogen, even after >22 000 bed volumes of treated water. GAC also effectively removed preformed DBPs at plants using prechlorination, including highly toxic iodoacetic acids and haloacetonitriles. However, 7 DBPs (mostly brominated and nitrogenous) increased in formation after GAC treatment. In one plant, an increase in tribromonitromethane had significant impacts on calculated cytotoxicity, which only had 7-17% reduction following GAC. While these DBPs are highly toxic, the total calculated cytotoxicity and genotoxicity for the GAC treated waters for the other two plants was reduced 32-83% (across young-middle-old GAC). Overall, calculated toxicity was reduced post-GAC, with preoxidation allowing further reductions. DA - 2019/5/21/ PY - 2019/5/21/ DO - 10.1021/acs.est.9b00023 VL - 53 IS - 10 SP - 5987-5999 SN - 1520-5851 ER - TY - JOUR TI - Adipocytes as Anticancer Drug Delivery Depot AU - Wen, Di AU - Wang, Jinqiang AU - Van Den Driessche, George AU - Chen, Qian AU - Zhang, Yuqi AU - Chen, Guojun AU - Li, Hongjun AU - Soto, Jennifer AU - Liu, Ming AU - Ohashi, Masao AU - Wang, Zejun AU - Abdou, Peter AU - Hu, Quanyin AU - Dotti, Gianpietro AU - Li, Song AU - Fourches, Denis AU - Gu, Zhen T2 - MATTER AB - Tumor-associated adipocytes promote tumor growth by providing energy and causing chronic inflammation. Here, we have exploited the lipid metabolism to engineer adipocytes that serve as a depot to deliver cancer therapeutics at the tumor site. Rumenic acid (RA), as an anticancer fatty acid, and a doxorubicin prodrug (pDox) with a reactive oxygen species (ROS)-cleavable linker, are encapsulated in adipocytes to deliver therapeutics in a tumor-specific bioresponsive manner. After intratumoral or postsurgical administration, lipolysis releases the RA and pDox that is activated by intracellular ROS-responsive conversion, subsequently promoting antitumor efficacy. Furthermore, downregulation of PD-L1 expression is observed in tumor cells, favoring the emergence of CD4+ and CD8+ T cell-mediated immune responses. DA - 2019/11/6/ PY - 2019/11/6/ DO - 10.1016/j.matt.2019.08.007 VL - 1 IS - 5 SP - 1203-1214 SN - 2590-2385 ER - TY - JOUR TI - Endocrine Disruption and Reproductive Pathology AU - Belcher, Scott M. AU - Cline, J. Mark AU - Conley, Justin AU - Groeters, Sibylle AU - Jefferson, Wendy N. AU - Law, Mac AU - Mackey, Emily AU - Suen, Alisa A. AU - Williams, Carmen J. AU - Dixon, Darlene AU - Wolf, Jeffrey C. T2 - TOXICOLOGIC PATHOLOGY AB - During the past 20 years, investigations involving endocrine active substances (EAS) and reproductive toxicity have dominated the landscape of ecotoxicological research. This has occurred in concert with heightened awareness in the scientific community, general public, and governmental entities of the potential consequences of chemical perturbation in humans and wildlife. The exponential growth of experimentation in this field is fueled by our expanding knowledge into the complex nature of endocrine systems and the intricacy of their interactions with xenobiotic agents. Complicating factors include the ever-increasing number of novel receptors and alternate mechanistic pathways that have come to light, effects of chemical mixtures in the environment versus those of single EAS laboratory exposures, the challenge of differentiating endocrine disruption from direct cytotoxicity, and the potential for transgenerational effects. Although initially concerned with EAS effects chiefly in the thyroid glands and reproductive organs, it is now recognized that anthropomorphic substances may also adversely affect the nervous and immune systems via hormonal mechanisms and play substantial roles in metabolic diseases, such as type 2 diabetes and obesity. DA - 2019/12// PY - 2019/12// DO - 10.1177/0192623319879903 VL - 47 IS - 8 SP - 1049-1071 SN - 1533-1601 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85076490433&partnerID=MN8TOARS KW - endocrine disrupters KW - environmental toxicology KW - fish pathology KW - hormonal carcinogenesis KW - reproductive system KW - nonhuman primate KW - rodent pathology ER - TY - JOUR TI - Mass spectrometry imaging (MSI) of fresh bones using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) AU - Khodjaniyazova, Sitora AU - Hanne, Nicholas J. AU - Cole, Jacqueline H. AU - Muddiman, David C. T2 - ANALYTICAL METHODS AB - Direct analysis and IR-MALDESI mass spectrometry imaging of fresh mouse bones that underwent no chemical treatments other than flash-freezing. DA - 2019/12/14/ PY - 2019/12/14/ DO - 10.1039/c9ay01886g VL - 11 IS - 46 SP - 5929-5938 SN - 1759-9679 ER - TY - JOUR TI - 1,4-Dioxane in drinking water: emerging for 40 years and still unregulated AU - McElroy, Amie C. AU - Hyman, Michael R. AU - Knappe, Detlef R.U. T2 - Current Opinion in Environmental Science & Health AB - The likely human carcinogen 1,4-dioxane was first detected in drinking water more than 40 years ago, and a recent analysis suggests that almost 30 million people in the United States receive drinking water with 1,4-dioxane levels above the health-based reference concentration of 0.35 μg/L. The widespread occurrence of 1,4-dioxane has exposed the need for developing and implementing management and treatment approaches that protect drinking water sources and prevent human exposure to 1,4-dioxane through drinking water. In this review, we highlight recent advances in analytical methods, understanding of occurrence, and treatment processes. Findings are discussed in the context of managing 1,4-dioxane as a drinking water contaminant, and recommendations are made to address important knowledge gaps. DA - 2019/2// PY - 2019/2// DO - 10.1016/j.coesh.2019.01.003 VL - 7 SP - 117-125 J2 - Current Opinion in Environmental Science & Health LA - en OP - SN - 2468-5844 UR - http://dx.doi.org/10.1016/j.coesh.2019.01.003 DB - Crossref ER - TY - JOUR TI - Metamodels to assess the thermal performance of naturally ventilated, low-cost houses in Brazil AU - Rossi, Michele Marta AU - Oliveira Favretto, Ana Paula AU - Grassi, Camila AU - DeCarolis, Joseph AU - Cho, Soolyeon AU - Hill, David AU - Soares Chvatal, Karin Maria AU - Ranjithan, Ranji T2 - ENERGY AND BUILDINGS AB - Building performance simulation [BPS] tools are important in all design stages. However, barriers such as time, resources, and expertise inhibit their use in the early design stages. This study aims to develop, as part of decision-support framework, metamodels to assess the thermal discomfort in a naturally ventilated Brazilian low-cost house during early design. The metamodels predict the degree-hours of discomfort by heat and/or by cold as a function of design parameters for three Brazilian cities: Curitiba, São Paulo, and Manaus. The key design parameters, related with passive design strategies, are building orientation, shading devices position and dimensions, thermal properties of the walls and roof, window-to-wall ratio, and effective window ventilation area. The method consists of three main stages: (i) baseline model development; (ii) Monte Carlo simulation; (iii) multivariate regression. Overall, the metamodels showed R2 values higher than 0.95 for all climates, except the ones predicting discomfort by heat for Curitiba (R2 =0.61) and São Paulo (R2 =0.75). The proposed metamodels can quickly and accurately assess the thermal performance of naturally ventilated low-cost houses. They can be used to guide professionals during the early design stages, and for educational purposes in building design pedagogy. DA - 2019/12/1/ PY - 2019/12/1/ DO - 10.1016/j.enbuild.2019.109457 VL - 204 SP - SN - 1872-6178 KW - Passive design KW - Natural ventilation KW - Metamodel KW - Multivariate regression KW - Early design ER - TY - JOUR TI - Fate of Per- and Polyfluoroalkyl Ether Acids in the Total Oxidizable Precursor Assay and Implications for the Analysis of Impacted Water AU - Zhang, Chuhui AU - Hopkins, Zachary R. AU - McCord, James AU - Strynar, Mark J. AU - Knappe, Detlef R. U. T2 - Environmental Science & Technology Letters AB - Per- and polyfluoroalkyl substances (PFASs) are widely used anthropogenic chemicals. The PFAS class includes almost 5000 registered compounds, but analytical methods are lacking for most PFASs. The total oxidizable precursor (TOP) assay was developed to indirectly quantify unknown PFASs that are precursors to commonly measured perfluoroalkyl acids. To understand the behavior of recently identified per- and polyfluoroalkyl ether acids (PFEAs), including fluorinated replacements and manufacturing byproducts, we determined the fate of 15 PFEAs in the TOP assay. Ten perfluoroalkyl ether acids and a chlorinated polyfluoroalkyl ether acid (F-53B) were stable in the TOP assay and represent terminal products that are likely as persistent as historically used PFASs. Adding perfluoroalkyl ether acids and F-53B to the target analyte list for the TOP assay is recommended to capture a higher percentage of the total PFAS concentration in environmental samples. In contrast, polyfluoroalkyl ether acids with a -O-CFH- moiety were oxidized, typically to products that could not be identified by liquid chromatography and high-resolution mass spectrometry. Application of the TOP assay in its proposed enhanced form revealed high levels of PFEAs, the presence of precursors that form perfluoroalkyl carboxylic acids, and the absence of precursors that form PFEAs in surface water impacted by PFAS-containing wastewater discharges. DA - 2019/10/2/ PY - 2019/10/2/ DO - 10.1021/acs.estlett.9b00525 VL - 6 IS - 11 SP - 662-668 J2 - Environ. Sci. Technol. Lett. LA - en OP - SN - 2328-8930 2328-8930 UR - http://dx.doi.org/10.1021/acs.estlett.9b00525 DB - Crossref ER - TY - JOUR TI - Folding and Assembly of Short α, β, Î-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures AU - Zhang, Y. AU - Zhong, Y. AU - Connor, A.L. AU - Miller, D.P. AU - Cao, R. AU - Shen, J. AU - Song, B. AU - Baker, E.S. AU - Tang, Q. AU - Pulavarti, S.V.S.R.K. AU - Liu, R. AU - Wang, Q. AU - Lu, Z.-L. AU - Szyperski, T. AU - Zeng, H. AU - Li, X. AU - Smith, R.D. AU - Zurek, E. AU - Zhu, J. AU - Gong, B. T2 - Journal of the American Chemical Society AB - Multilevel protein structures typically involve polypeptides of sufficient lengths. Here we report the folding and assembly of seven short tetrapeptides sharing the same types of α-, β-, and aromatic γ-amino acid residues. These are two sets of hybrid peptides, with three members in one set and four in the other, having complementary hydrogen-bonding sequences that were hypothesized to pair into linear H-bonded duplexes. However, instead of undergoing the anticipated pairing, the initially examined three oligomers, 1 and 2a or 2b, differing only in their central αβ hybrid dipeptide sequence, do not associate with each other and exhibit distinctly different folding behavior. Experiments based on NMR and mass spectrometry, along with computational studies and systematic inference, reveal that oligomer 1 folds into an expanded β-turn containing an unusual hybrid α/β-amino acid sequence composed of glycine and β-alanine, two α- and β-amino acid residues that are conformationally most flexible, and peptides 2a and 2b adopt a noncanonical, extended helical conformation and dimerize into double helices undergoing rapid conformational exchange or helix inversion. The different central dipeptide sequences, αβ vs βα, result in drastically different intramolecular H-bonding patterns that are responsible for the observed folding behavior of 1 and 2. The revealed turn and double helix have few natural or synthetic counterparts, and provide novel and unique folding prototypes based on which chiral α- and β-amino acids are incorporated. The resultant derivatives 1a, 1b, 2c, and 2d follow the same folding and assembling behavior and demonstrate the generality of this system with the formation of expanded β-turns and double helices with enhanced folding stabilities, hampered helix inversion, as well as defined and dominant helical sense. This work has demonstrated the unique capability of synthetic foldamers in generating structures with fascinating folding and assembling behavior. The revealed systems offer ample opportunity for further structural optimization and applications. DA - 2019/// PY - 2019/// DO - 10.1021/jacs.9b06094 VL - 141 IS - 36 SP - 14239-14248 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85072057414&partnerID=MN8TOARS ER - TY - BOOK TI - Ion Mobility-Mass Spectrometry in Metabolomic, Lipidomic, and Proteomic Analyses AU - Chouinard, C.D. AU - Nagy, G. AU - Smith, R.D. AU - Baker, E.S. AB - Ion mobility-mass spectrometry (IMS-MS) is rapidly gaining attention for improving metabolomic, lipidomic and proteomic analyses. Through the simultaneous measurement of molecular structures and mass, IMS-MS enables more complete analysis of mixtures, more confident molecular assignments, the construction of multicharacteristic molecular libraries, and the evaluation of unknown features in complex samples. Studies over the last decade have utilized IMS-MS to distinguish and study structurally similar small molecules, such as glycan anomers, polycyclic aromatic hydrocarbons, and lipid double bond isomers, leading to the discovery of new compounds with potentially high biological importance. Furthermore, IMS-MS has become an advanced proteomics tool not only for bottom-up peptide identification and quantitation but also for the study of native/intact proteins and their role in structural biology and disease progression. Additionally, recent advances in higher resolution IMS separations and its successful coupling with other preseparation, fragmentation, and characterization illustrate how IMS-MS will allow a more in-depth look into complex systems and further advance omics measurements. DA - 2019/// PY - 2019/// DO - 10.1016/bs.coac.2018.11.001 VL - 83 SE - 123-159 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85058397105&partnerID=MN8TOARS ER - TY - JOUR TI - Sex-specific effects of perinatal FireMaster® 550 (FM 550) exposure on socioemotional behavior in prairie voles AU - Gillera, S.E.A. AU - Marinello, W.P. AU - Horman, B.M. AU - Phillips, A.L. AU - Ruis, M.T. AU - Stapleton, H.M. AU - Reif, D.M. AU - Patisaul, H.B. T2 - Neurotoxicology and Teratology AB - The rapidly rising incidence of neurodevelopmental disorders with social deficits is raising concern that developmental exposure to environmental contaminants may be contributory. Firemaster 550 (FM 550) is one of the most prevalent flame-retardant (FR) mixtures used in foam-based furniture and baby products and contains both brominated and organophosphate components. We and others have published evidence of developmental neurotoxicity and sex specific effects of FM 550 on anxiety-like and exploratory behaviors. Using a prosocial animal model, we investigated the impact of perinatal FM 550 exposure on a range of socioemotional behaviors including anxiety, attachment, and memory. Virtually unknown to toxicologists, but widely used in the behavioral neurosciences, the prairie vole (Microtus ochrogaster) is a uniquely valuable model organism for examining environmental factors on sociality because this species is spontaneously prosocial, biparental, and displays attachment behaviors including pair bonding. Dams were exposed to 0, 500, 1000, or 2000 μg of FM 550 via subcutaneous (sc) injections throughout gestation, and pups were directly exposed beginning the day after birth until weaning. Adult offspring of both sexes were then subjected to multiple tasks including open field, novel object recognition, and partner preference. Effects were dose responsive and sex-specific, with females more greatly affected. Exposure-related outcomes in females included elevated anxiety, decreased social interaction, decreased exploratory motivation, and aversion to novelty. Exposed males also had social deficits, with males in all three dose groups failing to show a partner preference. Our studies demonstrate the utility of the prairie vole for investigating the impact of chemical exposures on social behavior and support the hypothesis that developmental FR exposure impacts the social brain. Future studies will probe the possible mechanisms by which these effects arise. DA - 2019/// PY - 2019/// DO - 10.1016/j.ntt.2019.106840 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85075415752&partnerID=MN8TOARS KW - Social KW - Anxiety KW - Brain KW - Neurodevelopment KW - Neural KW - Endocrine disruptors KW - Endocrine disrupting chemicals KW - Flame retardants ER - TY - JOUR TI - Multivariate modeling of engineered nanomaterial features associated with developmental toxicity AU - To, K.T. AU - Truong, L. AU - Edwards, S. AU - Tanguay, R.L. AU - Reif, D.M. T2 - NanoImpact AB - Despite the increasing prevalence of engineered nanomaterials (ENMs) in consumer products, their toxicity profiles remain to be elucidated. ENM physicochemical characteristics (PCC) are known to influence ENM behavior, however the mechanisms of these effects have not been quantified. Further confounding the question of how the PCC influence behavior is the inclusion of structural and molecular descriptors in modeling schema that minimize the effects of PCC on the toxicological endpoints. In this work, we analyze ENM physico-chemical measurements that have not previously been studied within a developmental toxicity framework using an embryonic zebrafish model. In testing a panel of diverse ENMs to build a consensus model, we found nonlinear relationships between any singular PCC and bioactivity. By using a machine learning (ML) method to characterize the information content of combinatorial PCC sets, we found that concentration, surface area, shape, and polydispersity can accurately capture the developmental toxicity profile of ENMs with consideration to whole-organism effects. DA - 2019/// PY - 2019/// DO - 10.1016/j.impact.2019.100185 VL - 16 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85074781270&partnerID=MN8TOARS KW - Engineered nanomaterials KW - Predictive modeling KW - Feature analysis KW - Developmental toxicity KW - Zebrafish ER - TY - JOUR TI - Synergistic Chemotherapy Drug Response Is a Genetic Trait in Lymphoblastoid Cell Lines AU - Roell, Kyle R. AU - Havener, Tammy M. AU - Reif, David M. AU - Jack, John AU - McLeod, Howard L. AU - Wiltshire, Tim AU - Motsinger-Reif, Alison A. T2 - FRONTIERS IN GENETICS AB - Lymphoblastoid cell lines (LCLs) are a highly successful model for evaluating the genetic etiology of cancer drug response, but applications using this model have typically focused on single drugs. Combination therapy is quite common in modern chemotherapy treatment since drugs often work synergistically, and it is an important progression in the use of the LCL model to expand work for drug combinations. In the present work, we demonstrate that synergy occurs and can be quantified in LCLs across a range of clinically important drug combinations. Lymphoblastoid cell lines have been commonly employed in association mapping in cancer pharmacogenomics, but it is so far untested as to whether synergistic effects have a genetic etiology. Here we use cell lines from extended pedigrees to demonstrate that there is a substantial heritable component to synergistic drug response. Additionally, we perform linkage mapping in these pedigrees to identify putative regions linked to this important phenotype. This demonstration supports the premise of expanding the use of the LCL model to perform association mapping for combination therapies. DA - 2019/10/15/ PY - 2019/10/15/ DO - 10.3389/fgene.2019.00829 VL - 10 SP - SN - 1664-8021 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85074258240&partnerID=MN8TOARS KW - synergy KW - heritability KW - chemotherapy KW - lymphoblastoid cell lines KW - linkage mapping ER - TY - JOUR TI - Ion Mobility Spectrometry: Fundamental Concepts, Instrumentation, Applications, and the Road Ahead AU - Dodds, James N. AU - Baker, Erin S. T2 - JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY AB - Ion mobility spectrometry (IMS) is a rapid separation technique that has experienced exponential growth as a field of study. Interfacing IMS with mass spectrometry (IMS-MS) provides additional analytical power as complementary separations from each technique enable multidimensional characterization of detected analytes. IMS separations occur on a millisecond timescale, and therefore can be readily nested into traditional GC and LC/MS workflows. However, the continual development of novel IMS methods has generated some level of confusion regarding the advantages and disadvantages of each. In this critical insight, we aim to clarify some common misconceptions for new users in the community pertaining to the fundamental concepts of the various IMS instrumental platforms (i.e., DTIMS, TWIMS, TIMS, FAIMS, and DMA), while addressing the strengths and shortcomings associated with each. Common IMS-MS applications are also discussed in this review, such as separating isomeric species, performing signal filtering for MS, and incorporating collision cross-section (CCS) values into both targeted and untargeted omics-based workflows as additional ion descriptors for chemical annotation. Although many challenges must be addressed by the IMS community before mobility information is collected in a routine fashion, the future is bright with possibilities. DA - 2019/11// PY - 2019/11// DO - 10.1007/s13361-019-02288-2 VL - 30 IS - 11 SP - 2185-2195 SN - 1879-1123 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85073982332&partnerID=MN8TOARS KW - Ion mobility spectrometry KW - IMS KW - Untargeted metabolomics KW - Mass spectrometry ER - TY - JOUR TI - Internal Energy Deposition in Infrared Matrix-Assisted Laser Desorption Electrospray Ionization With and Without the Use of Ice as a Matrix AU - Tu, Anqi AU - Muddiman, David C. T2 - JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY AB - The internal energy deposited into analytes during the ionization process largely influences the extent of fragmentation, thus the appearance of the resulting mass spectrum. The internal energy distributions of a series of para-substituted benzyl pyridinium cations in liquid and solid-state generated by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) were measured using the survival yield method, of which results were subsequently compared with conventional electrospray ionization (ESI). The comparable mean internal energy values (e.g., 1.8–1.9 eV at a collision energy of 15 eV) and peak widths obtained with IR-MALDESI and ESI support that IR-MALDESI are essentially a soft ionization technique where analytes do not gain considerable internal energy during the laser-induced desorption process and/or lose energy during uptake into charged electrospray droplets. An unusual fragment ion, protonated pyridine, was only found for solid IR-MALDESI at relatively high collision energies, which is presumably resulted from direct ionization of the pre-charged analytes in form of salts. Analysis of tissue with an ice layer consistently yielded ion populations with higher internal energy than its counterpart without an ice layer, likely due to a substantially enhanced number of IR absorbers with ice. Further measurements with holo-myoglobin show that IR-MALDESI-MS retains the noncovalently bound heme-protein complexes under both native-like and denaturing conditions, while complete loss of the heme group occurred in denaturing ESI-MS, showing that the softness of IR-MALDESI is equivalent or superior to ESI for biomolecules. DA - 2019/11// PY - 2019/11// DO - 10.1007/s13361-019-02323-2 VL - 30 IS - 11 SP - 2380-2391 SN - 1879-1123 KW - Internal energy deposition KW - IR-MALDESI KW - Mass spectrometry imaging KW - Survival yield method KW - Thermometer ions KW - Ambient ionization ER - TY - JOUR TI - C/EBP beta suppresses keratinocyte autonomous type 1 IFN response and p53 to increase cell survival and susceptibility to UVB-induced skin cancer AU - Tam, Hann W. AU - Hall, Jonathan R. AU - Messenger, Zachary J. AU - Jima, Dereje D. AU - House, John S. AU - Linder, Keith AU - Smart, Robert C. T2 - CARCINOGENESIS AB - p53 is activated by DNA damage and oncogenic stimuli to regulate senescence, apoptosis and cell-cycle arrest, which are essential to prevent cancer. Here, we utilized UVB radiation, a potent inducer of DNA damage, p53, apoptosis and skin cancer to investigate the mechanism of CCAAT/enhancer binding protein-β (C/EBPβ) in regulating p53-mediated apoptosis in keratinocytes and to test whether the deletion of C/EBPβ in epidermis can protect mice from UVB-induced skin cancer. UVB-treatment of C/EBPβ skin conditional knockout (CKOβ) mice increased p53 protein levels in epidermis and enhanced p53-dependent apoptotic activity 3-fold compared with UVB-treated control mice. UVB increased C/EBPβ levels through a p53-dependent pathway and stimulated the formation of a C/EBPβ-p53 protein complex; knockdown of C/EBPβ increased p53 protein stability in keratinocytes. These results suggest a p53-C/EBPβ feedback loop, whereby C/EBPβ, a transcriptional target of a p53 pathway, functions as a survival factor by negatively regulating p53 apoptotic activity in response to DNA damage. RNAseq analysis of UVB-treated CKOβ epidermis unexpectedly revealed that type 1 interferon (IFN) pathway was the most highly enriched pathway. Numerous pro-apoptotic interferon stimulated genes were upregulated including some known to enhance p53 apoptosis. Our results indicate that p53 and IFN pathways function together in response to DNA damage to result in the activation of extrinsic apoptosis pathways and caspase 8 cleavage. Last, we observed CKOβ mice were resistant to UVB-induced skin cancer. Our results suggest that C/EBPβ represses apoptosis through keratinocyte autonomous suppression of the type 1 IFN response and p53 to increase cell survival and susceptibility to UVB-induced skin cancer. DA - 2019/9// PY - 2019/9// DO - 10.1093/carcin/bgz012 VL - 40 IS - 9 SP - 1099-1109 SN - 1460-2180 ER - TY - JOUR TI - Perspectives on Data Analysis in Metabolomics: Points of Agreement and Disagreement from the 2018 ASMS Fall Workshop AU - Baker, Erin S. AU - Patti, Gary J. T2 - JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY AB - In November 2018, the American Society for Mass Spectrometry hosted the Annual Fall Workshop on informatic methods in metabolomics. The Workshop included sixteen lectures presented by twelve invited speakers. The focus of the talks was untargeted metabolomics performed with liquid chromatography/mass spectrometry. In this review, we highlight five recurring topics that were covered by multiple presenters: (i) data sharing, (ii) artifacts and contaminants, (iii) feature degeneracy, (iv) database organization, and (v) requirements for metabolite identification. Our objective here is to present viewpoints that were widely shared among participants, as well as those in which varying opinions were articulated. We note that most of the presenting speakers employed different data processing software, which underscores the diversity of informatic programs currently being used in metabolomics. We conclude with our thoughts on the potential role of reference datasets as a step towards standardizing data processing methods in metabolomics. DA - 2019/10// PY - 2019/10// DO - 10.1007/s13361-019-02295-3 VL - 30 IS - 10 SP - 2031-2036 SN - 1879-1123 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85071321181&partnerID=MN8TOARS KW - Metabolomics KW - Informatics KW - ASMS Fall Workshop KW - Metabolism ER - TY - JOUR TI - Maternal cadmium exposure in the mouse leads to increased heart weight at birth and programs susceptibility to hypertension in adulthood AU - Hudson, Kathleen M. AU - Belcher, Scott M. AU - Cowley, Michael T2 - SCIENTIFIC REPORTS AB - Abstract Cadmium (Cd) is a toxic heavy metal ubiquitous in the environment. Maternal exposure to Cd is associated with fetal growth restriction, trace element deficiencies, and congenital malformations. Cd exposure during adulthood is associated with cardiovascular disease (CVD); however, the effects of maternal Cd exposure on offspring cardiovascular development and disease are not well-understood. Utilizing a mouse model of maternal Cd exposure, we show that offspring born to Cd-exposed mothers have increased heart weights at birth and susceptibility to hypertension during adulthood. Despite inefficient maternal-fetal transfer of Cd, maternal Cd alters fetal levels of essential trace elements including a deficiency in iron, which is required for cardiovascular system development, oxygen homeostasis, and cellular metabolism. RNA-seq on newborn hearts identifies differentially expressed genes associated with maternal Cd exposure that are enriched for functions in CVD, hypertension, enlarged hearts, cellular energy, and hypoxic stress. We propose that a maternal Cd exposure-induced iron deficiency leads to altered cellular metabolic pathways and hypoxic conditions during fetal development; this stress may contribute to increased heart weight at birth and the programming of susceptibility to hypertension in adulthood. These studies will give insights into potential mechanisms through which maternal Cd exposure impacts cardiovascular development and disease. DA - 2019/9/19/ PY - 2019/9/19/ DO - 10.1038/s41598-019-49807-5 VL - 9 IS - 1 SP - SN - 2045-2322 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85072393964&partnerID=MN8TOARS ER - TY - JOUR TI - Calcium imaging of primary canine sensory neurons: Small‐diameter neurons responsive to pruritogens and algogens AU - Ganchingco, Joy Rachel C. AU - Fukuyama, Tomoki AU - Yoder, Jeffrey A. AU - Bäumer, Wolfgang T2 - Brain and Behavior AB - Abstract Introduction Rodent primary sensory neurons are commonly used for studying itch and pain neurophysiology, but translation from rodents to larger mammals and humans is not direct and requires further validation to make correlations. Methods This study developed a primary canine sensory neuron culture from dorsal root ganglia (DRG) excised from cadaver dogs. Additionally, the canine DRG cell cultures developed were used for single‐cell ratiometric calcium imaging, with the activation of neurons to the following pruritogenic and algogenic substances: histamine, chloroquine, canine protease‐activated receptor 2 (PAR2) activating peptide (SLIGKT), compound 48/80, 5‐hydroxytryptamine receptor agonist (5‐HT), bovine adrenal medulla peptide (BAM8‐22), substance P, allyl isothiocyanate (AITC), and capsaicin. Results This study demonstrates a simple dissection and rapid processing of DRG collected from canine cadavers used to create viable primary sensory neuron cultures to measure responses to pruritogens and algogens. Conclusion Ratiometric calcium imaging demonstrated that small‐diameter canine sensory neurons can be activated by multiple stimuli, and a single neuron can react to both a pruritogenic stimulation and an algogenic stimulation. DA - 2019/12// PY - 2019/12// DO - 10.1002/brb3.1428 UR - https://doi.org/10.1002/brb3.1428 KW - dorsal laminectomy dissection KW - dorsal root ganglia cell culture KW - fura-2AM KW - ratiometric calcium imaging ER - TY - JOUR TI - 4D-quantitative structure-activity relationship modeling: making a comeback AU - Fourches, Denis AU - Ash, Jeremy T2 - EXPERT OPINION ON DRUG DISCOVERY AB - Introduction: Predictive Quantitative Structure-Activity Relationship (QSAR) modeling has become an essential methodology for rapidly assessing various properties of chemicals. The vast majority of these QSAR models utilize numerical descriptors derived from the two- and/or three-dimensional structures of molecules. However, the conformation-dependent characteristics of flexible molecules and their dynamic interactions with biological target(s) is/are not encoded by these descriptors, leading to limited prediction performances and reduced interpretability. 2D/3D QSAR models are successful for virtual screening, but typically suffer at lead optimization stages. That is why conformation-dependent 4D-QSAR modeling methods were developed two decades ago. However, these methods have always suffered from the associated computational cost. Recently, 4D-QSAR has been experiencing a significant come-back due to rapid advances in GPU-accelerated molecular dynamic simulations and modern machine learning techniques. Areas covered: Herein, the authors briefly review the literature regarding 4D-QSAR modeling and describe its modern workflow called MD-QSAR. Challenges and current limitations are also highlighted. Expert opinion: The development of hyper-predictive MD-QSAR models could represent a disruptive technology for analyzing, understanding, and optimizing dynamic protein-ligand interactions with countless applications for drug discovery and chemical toxicity assessment. Therefore, there has never been a better time and relevance for molecular modeling teams to engage in hyper-predictive MD-QSAR modeling. DA - 2019/12/2/ PY - 2019/12/2/ DO - 10.1080/17460441.2019.1664467 VL - 14 IS - 12 SP - 1227-1235 SN - 1746-045X KW - 4D descriptors KW - cheminformatics KW - QSAR KW - molecular dynamics ER - TY - JOUR TI - Quantitative proteomic analysis of tomato genotypes with differential cadmium tolerance AU - Reis Borges, Karina Lima AU - Salvato, Fernanda AU - Loziuk, Philip L. AU - Muddiman, David C. AU - Azevedo, Ricardo Antunes T2 - ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH DA - 2019/9// PY - 2019/9// DO - 10.1007/s11356-019-05766-y VL - 26 IS - 25 SP - 26039-26051 SN - 1614-7499 KW - Root proteome KW - Cd stress KW - Antioxidant KW - Redox KW - Cell wall KW - Metabolism ER - TY - JOUR TI - Circulating tumor cells exit circulation while maintaining multicellularity, augmenting metastatic potential. T2 - Journal of cell science AB - Metastasis accounts for the majority of all cancer deaths, yet the process remains poorly understood. A pivotal step in the metastasis process is the exiting of tumor cells from the circulation, a process known as extravasation. However, it is unclear how tumor cells extravasate and whether multicellular clusters of tumor cells possess the ability to exit as a whole or must first disassociate. In this study, we use in vivo zebrafish and mouse models to elucidate the mechanism tumor cells use to extravasate. We found that circulating tumor cells exit the circulation using the recently identified extravasation mechanism, angiopellosis, and do so as both clusters and individual cells. We further show that when melanoma and cervical cancer cells utilize this extravasation method to exit as clusters, they exhibit an increased ability to form tumors at distant sites through the expression of unique genetic profiles. Collectively, we present a new model for tumor cell extravasation of both individual and multicellular circulating tumor cells.This article has an associated First Person interview with the first author of the paper. DA - 2019/9/9/ PY - 2019/9/9/ DO - 10.1242/jcs.231563 UR - https://doi.org/10.1242/jcs.231563 KW - Angiopellosis KW - Circulating tumor cell cluster KW - Tumor cell extravasation KW - Cancer exodus hypothesis KW - Metastasis ER - TY - JOUR TI - Approaches to fill data gaps and evaluate process completeness in LCA-perspectives from solid waste management systems AU - Henriksen, Trine AU - Levis, James W. AU - Barlaz, Morton A. AU - Damgaard, Anders T2 - INTERNATIONAL JOURNAL OF LIFE CYCLE ASSESSMENT AB - Large data amounts are required in an LCA, but often, site-specific data are missing and less representative surrogate data must be used to fill data gaps. No standardized rules exist on how to address data gaps and process completeness. We suggest a systematic evaluation of process completeness, identification of data gaps, and application of surrogate values to fill the gaps. The study focus on foreground process data. A solid waste management (SWM) scenario was used to illustrate the suggested method. The expected input and output flows in a waste incineration model were identified based on legislation and expert judgment, after which process completeness scores were calculated and missing flows identified. To illustrate the use of different types of surrogate data to fill data gaps, data gaps were selected for 16 different parameters in five SWM processes. We compared the global warming potential (GWP) from using surrogate data, and from leaving the gap, to identify the data gaps where representative surrogate data should be used. The completeness score for the material inputs to waste incineration was 78%, and the missing flows were auxiliary fuels and precipitation chemicals. The completeness score for air emissions were between 38 and 50% with and without expert judgment. If only greenhouse gases were considered (CO2, CH4, and N2O), the completeness score would be 67%. Applying weighting factors according to the greenhouse gas contribution in the USA gave a completeness score of 94%. The system-wide data gaps, where representative surrogate data should be applied, were the CH4 release from composting; electricity generation efficiency of incineration; recovery efficiencies at a material recovery facility; and composition of the plastic, metal, and paper fractions in the household waste; in these cases, leaving the gap changed the GWP results by > 5%. Completeness evaluation should take into account the relevance and importance of flows; relevance depends on the considered life cycle impact methods and importance depends on the weighting of the different flows. The set of expected flows and evaluation of relevance and importance must be documented in a transparent manner. The choice of surrogate values to fill data gaps depends on the availability of secondary data and on whether the data gap matters, i.e., significantly affects the LCA results. The suggested method can be used to properly document the identification of missing flows and to select and apply surrogate values to fill the data gaps. DA - 2019/9// PY - 2019/9// DO - 10.1007/s11367-019-01592-z VL - 24 IS - 9 SP - 1587-1601 SN - 1614-7502 KW - Completeness KW - Data gaps KW - Surrogate values KW - Representativeness KW - Waste management KW - LCA ER - TY - JOUR TI - Systematic evaluation of repeatability of IR-MALDESI-MS and normalization strategies for correcting the analytical variation and improving image quality AU - Tu, Anqi AU - Muddiman, David C. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY AB - Mass spectrometry imaging is a powerful tool widely used in biological, clinical, and forensic research, but its often poor repeatability limits its application for quantitative and large-scale analysis. A systematic evaluation of infrared matrix-assisted laser desorption electrospray ionization mass spectrometry (IR-MALDESI-MS) repeatability in absolute ion abundances during short- and long-term experiments was carried out on liver slices from the same rat with minimal biological variability to be expected. Results of median %RSDs ranging from 14 to 45, pooled %RMADs ranging from 11 to 33, and Pearson correlation coefficients ranging from 0.83 to 1.00 demonstrated an acceptable repeatability of IR-MALDESI-MS. Normalization is commonly applied for the purpose of accounting for analytical variability of spectra generated from different runs so as to reveal real biological differences. Nine data normalization strategies were performed on the rat liver data sets to examine their effects on reducing analytical variation, and further on a hen ovary data set containing more morphological features for the investigation of their impact on ion images. Results demonstrated that the majority of normalization approaches benefit data quality to some extent, and local normalization methods significantly outperform their global counterparts, resulting in a reduction of median %RSD up to 22. Local median normalization was found to be promisingly robust for both homogeneous and heterogeneous samples. DA - 2019/9// PY - 2019/9// DO - 10.1007/s00216-019-01953-5 VL - 411 IS - 22 SP - 5729-5743 SN - 1618-2650 KW - IR-MALDESI KW - Mass spectrometry imaging KW - Repeatability KW - Normalization ER - TY - JOUR TI - Presence of cerebrospinal fluid antibodies associated with autoimmune encephalitis of humans in dogs with neurologic disease AU - Stafford, Emma G. AU - Kortum, Amanda AU - Castel, Aude AU - Green, Lauren AU - Lau, Jeanie AU - Early, Peter J. AU - Muñana, Karen R. AU - Mariani, Christopher L. AU - Yoder, Jeffrey A. AU - Olby, Natasha J. T2 - Journal of Veterinary Internal Medicine AB - Abstract Background Presumed autoimmune diseases affecting the central nervous system (CNS) of dogs are common. In people, antibodies against neuronal cell surface antigens that are associated with a wide variety of neurological syndromes have been identified. The presence of cerebrospinal fluid (CSF) autoantibodies that target neuronal cell surface proteins has not been reported in dogs with neurologic disorders. Objectives Autoantibodies to neuronal cell surface antigens can be found in the CSF of dogs with inflammatory CNS disease. Our aim was to determine whether 6 neuronal cell surface autoantibodies were present in the CSF of dogs diagnosed with inflammatory and noninflammatory CNS disease. Animals Client‐owned dogs with CNS disease and complete diagnostic evaluation including magnetic resonance imaging and CSF analysis were included. One healthy dog was included as a negative control. Methods Cerebrospinal fluid was tested for 6 antigenic targets with a commercially available indirect immunofluorescence assay test kit. Results There were 32 dogs with neurological disease, 19 diagnosed with inflammatory disease (encephalitis and meningitis), 10 with noninflammatory disease (neoplasia, intervertebral disk disease, degenerative myelopathy, and epilepsy), 2 with no diagnosis, and 1 with neoplasia and meningoencephalitis. Anti‐N‐methyl‐ d ‐aspartate receptor 1 (NMDAR1) antibodies were detected in 3 dogs (3/32; 9.38%). All 3 dogs responded to treatment of meningoencephalomyelitis of unknown etiology (MUE). Conclusions and Clinical Importance Further evaluation of the prevalence and clinical relevance of CSF and serum antibodies to neuronal cell surface antigens is warranted. Defining antigenic targets associated with encephalitis in dogs might allow diagnostic categorization of MUE antemortem. DA - 2019/9// PY - 2019/9// DO - 10.1111/jvim.15616 UR - https://doi.org/10.1111/jvim.15616 KW - immunofluorescent assay KW - meningoencephalitis KW - MUE KW - NMDA receptor encephalitis ER - TY - JOUR TI - Population-based toxicity screening in human induced pluripotent stem cell-derived cardiomyocytes AU - Burnett, S.D. AU - Blanchette, A.D. AU - Grimm, F.A. AU - House, J.S. AU - Reif, D.M. AU - Wright, F.A. AU - Chiu, W.A. AU - Rusyn, I. T2 - Toxicology and Applied Pharmacology AB - The potential for cardiotoxicity is carefully evaluated for pharmaceuticals, as it is a major safety liability. However, environmental chemicals are seldom tested for their cardiotoxic potential. Moreover, there is a large variability in both baseline and drug-induced cardiovascular risk in humans, but data are lacking on the degree to which susceptibility to chemically-induced cardiotoxicity may also vary. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes have become an important in vitro model for drug screening. Thus, we hypothesized that a population-based model of iPSC-derived cardiomyocytes from a diverse set of individuals can be used to assess potential hazard and inter-individual variability in chemical effects on these cells. We conducted concentration-response screening of 134 chemicals (pharmaceuticals, industrial and environmental chemicals and food constituents) in iPSC-derived cardiomyocytes from 43 individuals, comprising both sexes and diverse ancestry. We measured kinetic calcium flux and conducted high-content imaging following chemical exposure, and utilized a panel of functional and cytotoxicity parameters in concentration-response for each chemical and donor. We show reproducible inter-individual variability in both baseline and chemical-induced effects on iPSC-derived cardiomyocytes. Further, chemical-specific variability in potency and degree of population variability were quantified. This study shows the feasibility of using an organotypic population-based human in vitro model to quantitatively assess chemicals for which little cardiotoxicity information is available. Ultimately, these results advance in vitro toxicity testing methodologies by providing an innovative tool for population-based cardiotoxicity screening, contributing to the paradigm shift from traditional animal models of toxicity to in vitro toxicity testing methods. DA - 2019/10// PY - 2019/10// DO - 10.1016/j.taap.2019.114711 VL - 381 UR - http://dx.doi.org/10.1016/j.taap.2019.114711 KW - iPSC KW - In vitro KW - Alternative methods KW - Cardiotoxicity KW - High-content screening KW - Environmental chemicals ER - TY - JOUR TI - Integration of curated and high-throughput screening data to elucidate environmental influences on disease pathways AU - Kosnik, Marissa B. AU - Planchart, Antonio AU - Marvel, Skylar W. AU - Reif, David M. AU - Mattingly, Carolyn J. T2 - Computational Toxicology AB - Addressing the complex relationship between public health and environmental exposure requires multiple types and sources of data. An important source of chemical data derives from high-throughput screening (HTS) efforts, such as the Tox21/ToxCast program, which aim to identify chemical hazard using primarily in vitro assays to probe toxicity. While most of these assays target specific genes, assessing the disease-relevance of these assays remains challenging. Integration with additional data sets may help to resolve these questions by providing broader context for individual assay results. The Comparative Toxicogenomics Database (CTD), a publicly available database that builds networks of chemical, gene, and disease information from manually curated literature sources, offers a promising solution for contextual integration with HTS data. Here, we tested the value of integrating data across Tox21/ToxCast and CTD by linking elements common to both databases (i.e., assays, genes, and chemicals). Using polymarcine and Parkinson’s disease as a case study, we found that their union significantly increased chemical-gene associations and disease-pathway coverage. Integration also enabled new disease associations to be made with HTS assays, expanding coverage of chemical-gene data associated with diseases. We demonstrate how integration enables development of predictive adverse outcome pathways using 4-nonylphenol, branched as an example. Thus, we demonstrate enhancements to each data source through database integration, including scenarios where HTS data can efficiently probe chemical space that may be understudied in the literature, as well as how CTD can add biological context to those results. DA - 2019/11// PY - 2019/11// DO - 10.1016/j.comtox.2019.100094 VL - 12 SP - 100094 J2 - Computational Toxicology LA - en OP - SN - 2468-1113 UR - http://dx.doi.org/10.1016/j.comtox.2019.100094 DB - Crossref ER - TY - JOUR TI - Student-Guided Three-Dimensional Printing Activity in Large Lecture Courses: A Practical Guideline AU - Fourches, Denis AU - Feducia, Jeremiah T2 - JOURNAL OF CHEMICAL EDUCATION AB - Modern technology stimulates the development of innovative classroom activities. We designed a 3D printing activity in two separate Organic Chemistry lectures of at least 200 students each. This assignment required students to 3D print a molecule of their choice, relying on services made available through the university libraries. Data obtained through a survey at the end of the semester provided key information on the students’ experiences with printing 3D models for the first time. A summary of this feedback and constructive remarks on the best practices regarding 3D printing assignments in large lecture courses are presented. DA - 2019/2// PY - 2019/2// DO - 10.1021/acs.jchemed.8b00346 VL - 96 IS - 2 SP - 291-295 SN - 1938-1328 KW - Chemoinformatics KW - Organic Chemistry KW - Hands-On Learning/Manipulatives KW - First-Year Undergraduate/General KW - Second-Year Undergraduate ER - TY - JOUR TI - Heterogeneous antiretroviral drug distribution and HIV/SHIV detection in the gut of three species AU - Thompson, Corbin G. AU - Rosen, Elias P. AU - Prince, Heather M. A. AU - White, Nicole AU - Sykes, Craig AU - Cruz, Gabriela AU - Mathews, Michelle AU - Deleage, Claire AU - Estes, Jacob D. AU - Charlins, Paige AU - Mulder, Leila R. AU - Kovarova, Martina AU - Adamson, Lourdes AU - Arora, Shifali AU - Dellon, Evan S. AU - Peery, Anne F. AU - Shaheen, Nicholas J. AU - Gay, Cynthia AU - Muddiman, David C. AU - Akkina, Ramesh AU - Garcia, J. Victor AU - Luciw, Paul AU - Kashuba, Angela D. M. T2 - SCIENCE TRANSLATIONAL MEDICINE AB - Imaging reveals that antiretroviral drugs are not distributed evenly in the mammalian gut, with potential implications for HIV replication. DA - 2019/7/3/ PY - 2019/7/3/ DO - 10.1126/scitranslmed.aap8758 VL - 11 IS - 499 SP - SN - 1946-6242 ER - TY - JOUR TI - Evaluating the structural complexity of isomeric bile acids with ion mobility spectrometry AU - Zheng, Xueyun AU - Smith, Francesca B. AU - Aly, Noor A. AU - Cai, Jingwei AU - Smith, Richard D. AU - Patterson, Andrew D. AU - Baker, Erin S. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY AB - Bile acids (BAs) play an integral role in digestion through the absorption of nutrients, emulsification of fats and fat-soluble vitamins, and maintenance of cholesterol levels. Metabolic disruption, diabetes, colorectal cancer, and numerous other diseases have been linked with BA disruption, making improved BA analyses essential. To date, most BA measurements are performed using liquid chromatography separations in conjunction with mass spectrometry measurements (LC-MS). However, 10–40 min LC gradients are often used for BA analyses and these may not even be sufficient for distinguishing all the important isomers present in the human body. Ion mobility spectrometry (IMS) is a promising tool for BA evaluations due to its ability to quickly separate isomeric molecules with subtle structural differences. In this study, we utilized drift tube IMS (DTIMS) coupled with MS to characterize 56 different unlabeled BA standards and 16 deuterated versions. In the DTIMS-MS analyses of 12 isomer groups, BAs with smaller m/z values were easily separated in either their deprotonated or sodiated forms (or both). However, as the BAs grew in m/z value, they became more difficult to separate with two isomer groups being inseparable. Metal ions such as copper and zinc were then added to the overlapping BAs, and due to different binding sites, the resulting complexes were separable. Thus, the rapid structural measurements possible with DTIMS-MS show great potential for BAs measurements with and without prior LC separations. DA - 2019/7// PY - 2019/7// DO - 10.1007/s00216-019-01869-0 VL - 411 IS - 19 SP - 4673-4682 SN - 1618-2650 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85066032454&partnerID=MN8TOARS KW - Ion mobility spectrometry KW - Bile acids KW - Collisional cross sections ER - TY - JOUR TI - Evaluation of optimal model parameters for prediction of methane generation from selected US landfills AU - Sun, Wenjie AU - Wang, Xiaoming AU - DeCarolis, Joseph F. AU - Barlaz, Morton A. T2 - WASTE MANAGEMENT AB - In practice, methane generation at U.S. landfills is typically predicted by using the EPA's Landfill Gas Emissions Model (LandGEM), which includes two parameters, the methane production potential (L0, m3 CH4 Mg-1 wet waste) and the first-order decay rate constant (k, yr-1). Default parameters in LandGEM (L0 = 100 and k = 0.04) were determined using data that reflect landfill management practices in the 1990s. In this study, methane collection data from 21 U.S. landfills were used to estimate the best fit k by inverse modeling of measured methane collection data in consideration of a time-varying gas collection efficiency. Optimal values of k were identified at a range of L0s between 55 and 160. The best fit k was greater than the U.S. EPA's default parameter of 0.04 yr-1 at 14 of the 21 landfills studied. Surprisingly, the best fit k was often observed at L0 values greater than 100 m3 CH4 Mg-1 wet waste which again is the U.S. EPA default. The results show that there is wide variation in the best estimate of k. While there was a tendency for landfills, or sections of landfills that received more moisture to exhibit higher decay rates, the results were not consistent. Some landfills exhibited high decay rates even though the data suggested that they were relatively dry while some wet landfills exhibited low decay rates. The results suggest that L0 captures many factors and that the data may be most useful for site specific analysis as opposed to general landfill predictions. DA - 2019/5/15/ PY - 2019/5/15/ DO - 10.1016/j.wasman.2019.05.004 VL - 91 SP - 120-127 SN - 0956-053X KW - Landfills KW - Landfill gas KW - Methane KW - Gas collection efficiency KW - LandGEM ER - TY - JOUR TI - Label-Free Quantitative Proteomics of Enriched Nuclei from Sugarcane (Saccharum ssp) Stems in Response to Drought Stress AU - Salvato, Fernando AU - Loziuk, Philip AU - Kiyota, Eduardo AU - Daneluzzi, Gabriel Silva AU - Araujo, Pedro AU - Muddiman, David C. AU - Mazzafera, Paulo T2 - PROTEOMICS AB - Abstract Drought is considered the major abiotic stress limiting crop productivity. This study seeks to identify proteins involved in the drought response in sugarcane stems submitted to drought stress. The integration of nuclei enrichment sample preparation with the shotgun proteomic approach results in great coverage of the sugarcane stem proteome with 5381 protein groups identified. A total of 1204 differentially accumulated proteins are detected in response to drought, among which 586 and 618 are increased and reduced in abundance, respectively. A total of 115 exclusive proteins are detected, being 41 exclusives of drought‐stressed plants and 74 exclusives of control plants. In the control plants, most of these proteins are related to cell wall metabolism, indicating that drought affects negatively the cell wall metabolism. Also, 37 transcription factors (TFs) are identified, which are low abundant nuclear proteins and are differentially accumulated in response to drought stress. These TFs are associated to protein domains such as leucine‐rich (bZIP), C2H2, NAC, C3H, LIM, Myb‐related, heat shock factor (HSF) and auxin response factor (ARF). Increased abundance of chromatin remodeling and RNA processing proteins are also observed. It is suggested that these variations result from an imbalance of protein synthesis and degradation processes induced by drought. DA - 2019/7// PY - 2019/7// DO - 10.1002/pmic.201900004 VL - 19 IS - 14 SP - SN - 1615-9861 KW - drought KW - RNA regulation KW - Saccharum spp KW - shotgun proteomics KW - transcription factors ER - TY - JOUR TI - Determination of chemical-disease risk values to prioritize connections between environmental factors, genetic variants, and human diseases AU - Kosnik, Marissa B. AU - Reif, David M. T2 - Toxicology and Applied Pharmacology AB - Traditional methods for chemical risk assessment are too time-consuming and resource-intensive to characterize either the diversity of chemicals to which humans are exposed or how that diversity may manifest in population susceptibility differences. The advent of novel toxicological data sources and their integration with bioinformatic databases affords opportunities for modern approaches that consider gene-environment (GxE) interactions in population risk assessment. Here, we present an approach that systematically links multiple data sources to relate chemical risk values to diseases and gene-disease variants. These data sources include high-throughput screening (HTS) results from Tox21/ToxCast, chemical-disease relationships from the Comparative Toxicogenomics Database (CTD), hazard data from resources like the Integrated Risk Information System, exposure data from the ExpoCast initiative, and gene-variant-disease information from the DisGeNET database. We use these integrated data to identify variants implicated in chemical-disease enrichments and develop a new value that estimates the risk of these associations toward differential population responses. Finally, we use this value to prioritize chemical-disease associations by exploring the genomic distribution of variants implicated in high-risk diseases. We offer this modular approach, termed DisQGOS (Disease Quotient Genetic Overview Score), for relating overall chemical-disease risk to potential for population variable responses, as a complement to methods aiming to modernize aspects of risk assessment. DA - 2019/9// PY - 2019/9// DO - 10.1016/j.taap.2019.114674 VL - 379 SP - 114674 UR - https://doi.org/10.1016/j.taap.2019.114674 KW - Data integration KW - Risk assessment KW - New approach methodologies KW - Gene-environment interactions ER - TY - JOUR TI - Effects of Co-occurring Species Present in Swine Lagoons on Adsorption of Copper on Eggshell AU - Hess, Brianna J. AU - Kolar, Praveen AU - Classen, John J. AU - Knappe, Detlef AU - Cheng, Jay J. T2 - INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH DA - 2019/8// PY - 2019/8// DO - 10.1007/s41742-019-00203-x VL - 13 IS - 4 SP - 613-622 SN - 2008-2304 KW - Adsorption KW - Eggshell KW - Copper KW - Swine lagoons KW - Acetate KW - Ammonia ER - TY - JOUR TI - Cheminformatics approach to exploring and modeling trait-associated metabolite profiles AU - Ash, Jeremy R. AU - Kuenemann, Melaine A. AU - Rotroff, Daniel AU - Motsinger-Reif, Alison AU - Fourches, Denis T2 - JOURNAL OF CHEMINFORMATICS AB - Developing predictive and transparent approaches to the analysis of metabolite profiles across patient cohorts is of critical importance for understanding the events that trigger or modulate traits of interest (e.g., disease progression, drug metabolism, chemical risk assessment). However, metabolites’ chemical structures are still rarely used in the statistical modeling workflows that establish these trait-metabolite relationships. Herein, we present a novel cheminformatics-based approach capable of identifying predictive, interpretable, and reproducible trait-metabolite relationships. As a proof-of-concept, we utilize a previously published case study consisting of metabolite profiles from non-small-cell lung cancer (NSCLC) adenocarcinoma patients and healthy controls. By characterizing each structurally annotated metabolite using both computed molecular descriptors and patient metabolite concentration profiles, we show that these complementary features enhance the identification and understanding of key metabolites associated with cancer. Ultimately, we built multi-metabolite classification models for assessing patients’ cancer status using specific groups of metabolites identified based on high structural similarity through chemical clustering. We subsequently performed a metabolic pathway enrichment analysis to identify potential mechanistic relationships between metabolites and NSCLC adenocarcinoma. This cheminformatics-inspired approach relies on the metabolites’ structural features and chemical properties to provide critical information about metabolite-trait associations. This method could ultimately facilitate biological understanding and advance research based on metabolomics data, especially with respect to the identification of novel biomarkers. DA - 2019/6/24/ PY - 2019/6/24/ DO - 10.1186/s13321-019-0366-3 VL - 11 SP - SN - 1758-2946 KW - Metabolomics KW - Data mining KW - Cheminformatics KW - Molecular fragmentation KW - Statistics KW - Visualization KW - Chemical structure ER - TY - JOUR TI - Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen AU - Menden, Michael P. AU - Wang, Dennis AU - Mason, Mike J. AU - Szalai, Bence AU - Bulusu, Krishna C. AU - Guan, Yuanfang AU - Yu, Thomas AU - Kang, Jaewoo AU - Jeon, Minji AU - Wolfinger, Russ AU - Nguyen, Tin AU - Zaslavskiy, Mikhail AU - Jang, In Sock AU - Ghazoui, Zara AU - Ahsen, Mehmet Eren AU - Vogel, Robert AU - Neto, Elias Chaibub AU - Norman, Thea AU - Tang, Eric K. Y. AU - Garnett, Mathew J. AU - Di Veroli, Giovanni Y. AU - Fawell, Stephen AU - Stolovitzky, Gustavo AU - Guinney, Justin AU - Dry, Jonathan R. AU - Saez-Rodriguez, Julio AU - Abante, Jordi AU - Abecassis, Barbara Schmitz AU - Aben, Nanne AU - Aghamirzaie, Delasa AU - Aittokallio, Tero AU - Akhtari, Farida S. AU - Al-lazikani, Bissan AU - Alam, Tanvir AU - Allam, Amin AU - Allen, Chad AU - Almeida, Mariana Pelicano AU - Altarawy, Doaa AU - Alves, Vinicius AU - Amadoz, Alicia AU - Anchang, Benedict AU - Antolin, Albert A. AU - Ash, Jeremy R. AU - Romeo Aznar, Victoria AU - Ba-alawi, Wail AU - Bagheri, Moeen AU - Bajic, Vladimir AU - Ball, Gordon AU - Ballester, Pedro J. AU - Baptista, Delora AU - Bare, Christopher AU - Bateson, Mathilde AU - Bender, Andreas AU - Bertrand, Denis AU - Wijayawardena, Bhagya AU - Boroevich, Keith A. AU - Bosdriesz, Evert AU - Bougouffa, Salim AU - Bounova, Gergana AU - Brouwer, Thomas AU - Bryant, Barbara AU - Calaza, Manuel AU - Calderone, Alberto AU - Calza, Stefano AU - Capuzzi, Stephen AU - Carbonell-Caballero, Jose AU - Carlin, Daniel AU - Carter, Hannah AU - Castagnoli, Luisa AU - Celebi, Remzi AU - Cesareni, Gianni AU - Chang, Hyeokyoon AU - Chen, Guocai AU - Chen, Haoran AU - Chen, Huiyuan AU - Cheng, Lijun AU - Chernomoretz, Ariel AU - Chicco, Davide AU - Cho, Kwang-Hyun AU - Cho, Sunghwan AU - Choi, Daeseon AU - Choi, Jaejoon AU - Choi, Kwanghun AU - Choi, Minsoo AU - De Cock, Martine AU - Coker, Elizabeth AU - Cortes-Ciriano, Isidro AU - Cserzo, Miklos AU - Cubuk, Cankut AU - Curtis, Christina AU - Van Daele, Dries AU - Dang, Cuong C. AU - Dijkstra, Tjeerd AU - Dopazo, Joaquin AU - Draghici, Sorin AU - Drosou, Anastasios AU - Dumontier, Michel AU - Ehrhart, Friederike AU - Eid, Fatma-Elzahraa AU - ElHefnawi, Mahmoud AU - Elmarakeby, Haitham AU - Engelen, Bo AU - Engin, Hatice Billur AU - Esch, Iwan AU - Evelo, Chris AU - Falcao, Andre O. AU - Farag, Sherif AU - Fernandez-Lozano, Carlos AU - Fisch, Kathleen AU - Flobak, Asmund AU - Fornari, Chiara AU - Foroushani, Amir B. K. AU - Fotso, Donatien Chedom AU - Fourches, Denis AU - Friend, Stephen AU - Frigessi, Arnoldo AU - Gao, Feng AU - Gao, Xiaoting AU - Gerold, Jeffrey M. AU - Gestraud, Pierre AU - Ghosh, Samik AU - Gillberg, Jussi AU - Godoy-Lorite, Antonia AU - Godynyuk, Lizzy AU - Godzik, Adam AU - Goldenberg, Anna AU - Gomez-Cabrero, David AU - Gonen, Mehmet AU - Graaf, Chris AU - Gray, Harry AU - Grechkin, Maxim AU - Guimera, Roger AU - Guney, Emre AU - Haibe-Kains, Benjamin AU - Han, Younghyun AU - Hase, Takeshi AU - He, Di AU - He, Liye AU - Heath, Lenwood S. AU - Hellton, Kristoffer H. AU - Helmer-Citterich, Manuela AU - Hidalgo, Marta R. AU - Hidru, Daniel AU - Hill, Steven M. AU - Hochreiter, Sepp AU - Hong, Seungpyo AU - Hovig, Eivind AU - Hsueh, Ya-Chih AU - Hu, Zhiyuan AU - Huang, Justin K. AU - Huang, R. Stephanie AU - Hunyady, Laszlo AU - Hwang, Jinseub AU - Hwang, Tae Hyun AU - Hwang, Woochang AU - Hwang, Yongdeuk AU - Isayev, Olexandr AU - Walk, Oliver Bear Don't AU - Jack, John AU - Jahandideh, Samad AU - Ji, Jiadong AU - Jo, Yousang AU - Kamola, Piotr J. AU - Kanev, Georgi K. AU - Karacosta, Loukia AU - Karimi, Mostafa AU - Kaski, Samuel AU - Kazanov, Marat AU - Khamis, Abdullah M. AU - Khan, Suleiman Ali AU - Kiani, Narsis A. AU - Kim, Allen AU - Kim, Jinhan AU - Kim, Juntae AU - Kim, Kiseong AU - Kim, Kyung AU - Kim, Sunkyu AU - Kim, Yongsoo AU - Kim, Yunseong AU - Kirk, Paul D. W. AU - Kitano, Hiroaki AU - Klambauer, Gunter AU - Knowles, David AU - Ko, Melissa AU - Kohn-Luque, Alvaro AU - Kooistra, Albert J. AU - Kuenemann, Melaine A. AU - Kuiper, Martin AU - Kurz, Christoph AU - Kwon, Mijin AU - Laarhoven, Twan AU - Laegreid, Astrid AU - Lederer, Simone AU - Lee, Heewon AU - Lee, Jeon AU - Lee, Yun Woo AU - Leppaho, Eemeli AU - Lewis, Richard AU - Li, Jing AU - Li, Lang AU - Liley, James AU - Lim, Weng Khong AU - Lin, Chieh AU - Liu, Yiyi AU - Lopez, Yosvany AU - Low, Joshua AU - Lysenko, Artem AU - Machado, Daniel AU - Madhukar, Neel AU - De Maeyer, Dries AU - Malpartida, Ana Belen AU - Mamitsuka, Hiroshi AU - Marabita, Francesco AU - Marchal, Kathleen AU - Marttinen, Pekka AU - Mason, Daniel AU - Mazaheri, Alireza AU - Mehmood, Arfa AU - Mehreen, Ali AU - Michaut, Magali AU - Miller, Ryan A. AU - Mitsopoulos, Costas AU - Modos, Dezso AU - Van Moerbeke, Marijke AU - Moo, Keagan AU - Motsinger-Reif, Alison AU - Movva, Rajiv AU - Muraru, Sebastian AU - Muratov, Eugene AU - Mushthofa, Mushthofa AU - Nagarajan, Niranjan AU - Nakken, Sigve AU - Nath, Aritro AU - Neuvial, Pierre AU - Newton, Richard AU - Ning, Zheng AU - De Niz, Carlos AU - Oliva, Baldo AU - Olsen, Catharina AU - Palmeri, Antonio AU - Panesar, Bhawan AU - Papadopoulos, Stavros AU - Park, Jaesub AU - Park, Seonyeong AU - Park, Sungjoon AU - Pawitan, Yudi AU - Peluso, Daniele AU - Pendyala, Sriram AU - Peng, Jian AU - Perfetto, Livia AU - Pirro, Stefano AU - Plevritis, Sylvia AU - Politi, Regina AU - Poon, Hoifung AU - Porta, Eduard AU - Prellner, Isak AU - Preuer, Kristina AU - Angel Pujana, Miguel AU - Ramnarine, Ricardo AU - Reid, John E. AU - Reyal, Fabien AU - Richardson, Sylvia AU - Ricketts, Camir AU - Rieswijk, Linda AU - Rocha, Miguel AU - Rodriguez-Gonzalvez, Carmen AU - Roell, Kyle AU - Rotroff, Daniel AU - Ruiter, Julian R. AU - Rukawa, Ploy AU - Sadacca, Benjamin AU - Safikhani, Zhaleh AU - Safitri, Fita AU - Sales-Pardo, Marta AU - Sauer, Sebastian AU - Schlichting, Moritz AU - Seoane, Jose A. AU - Serra, Jordi AU - Shang, Ming-Mei AU - Sharma, Alok AU - Sharma, Hari AU - Shen, Yang AU - Shiga, Motoki AU - Shin, Moonshik AU - Shkedy, Ziv AU - Shopsowitz, Kevin AU - Sinai, Sam AU - Skola, Dylan AU - Smirnov, Petr AU - Soerensen, Izel Fourie AU - Soerensen, Peter AU - Song, Je-Hoon AU - Song, Sang Ok AU - Soufan, Othman AU - Spitzmueller, Andreas AU - Steipe, Boris AU - Suphavilai, Chayaporn AU - Tamayo, Sergio Pulido AU - Tamborero, David AU - Tang, Jing AU - Tanoli, Zia-ur-Rehman AU - Tarres-Deulofeu, Marc AU - Tegner, Jesper AU - Thommesen, Liv AU - Tonekaboni, Seyed Ali Madani AU - Tran, Hong AU - De Troyer, Ewoud AU - Truong, Amy AU - Tsunoda, Tatsuhiko AU - Turu, Gabor AU - Tzeng, Guang-Yo AU - Verbeke, Lieven AU - Videla, Santiago AU - Vis, Daniel AU - Voronkov, Andrey AU - Votis, Konstantinos AU - Wang, Ashley AU - Wang, Hong-Qiang Horace AU - Wang, Po-Wei AU - Wang, Sheng AU - Wang, Wei AU - Wang, Xiaochen AU - Wang, Xin AU - Wennerberg, Krister AU - Wernisch, Lorenz AU - Wessels, Lodewyk AU - Westen, Gerard J. P. AU - Westerman, Bart A. AU - White, Simon Richard AU - Willighagen, Egon AU - Wurdinger, Tom AU - Xie, Lei AU - Xie, Shuilian AU - Xu, Hua AU - Yadav, Bhagwan AU - Yau, Christopher AU - Yeerna, Huwate AU - Yin, Jia Wei AU - Yu, Michael AU - Yu, MinHwan AU - Yun, So Jeong AU - Zakharov, Alexey AU - Zamichos, Alexandros AU - Zanin, Massimiliano AU - Zeng, Li AU - Zenil, Hector AU - Zhang, Frederick AU - Zhang, Pengyue AU - Zhang, Wei AU - Zhao, Hongyu AU - Zhao, Lan AU - Zheng, Wenjin AU - Zoufir, Azedine AU - Zucknick, Manuela T2 - NATURE COMMUNICATIONS AB - The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells. DA - 2019/6/17/ PY - 2019/6/17/ DO - 10.1038/s41467-019-09799-2 VL - 10 SP - SN - 2041-1723 ER - TY - JOUR TI - Challenges in Identifying the Dark Molecules of Life AU - Eugenia Monge, Maria AU - Dodds, James N. AU - Baker, Erin S. AU - Edison, Arthur S. AU - Fernandez, Facundo M. T2 - ANNUAL REVIEW OF ANALYTICAL CHEMISTRY, VOL 12 AB - Metabolomics is the study of the metabolome, the collection of small molecules in living organisms, cells, tissues, and biofluids. Technological advances in mass spectrometry, liquid- and gas-phase separations, nuclear magnetic resonance spectroscopy, and big data analytics have now made it possible to study metabolism at an omics or systems level. The significance of this burgeoning scientific field cannot be overstated: It impacts disciplines ranging from biomedicine to plant science. Despite these advances, the central bottleneck in metabolomics remains the identification of key metabolites that play a class-discriminant role. Because metabolites do not follow a molecular alphabet as proteins and nucleic acids do, their identification is much more time consuming, with a high failure rate. In this review, we critically discuss the state-of-the-art in metabolite identification with specific applications in metabolomics and how technologies such as mass spectrometry, ion mobility, chromatography, and nuclear magnetic resonance currently contribute to this challenging task. DA - 2019/// PY - 2019/// DO - 10.1146/annurev-anchem-061318-114959 VL - 12 SP - 177-199 SN - 1936-1327 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85067284122&partnerID=MN8TOARS KW - metabolomics KW - metabolite identification KW - chromatography KW - ion mobility KW - tandem mass spectrometry KW - nuclear magnetic resonance spectroscopy ER - TY - JOUR TI - High Temperature Co-pyrolysis Thermal Air Activation Enhances Biochar Adsorption of Herbicides from Surface Water AU - Kearns, Joshua P. AU - Shimabuku, Kyle K. AU - Knappe, Detlef R. U. AU - Summers, R. Scott T2 - ENVIRONMENTAL ENGINEERING SCIENCE AB - Recent interest has arisen in the use of biochar as a low-cost adsorbent for control of organic micropollutants in water. However, compared with activated carbon (AC), biochar adsorption capacity is typically one to two orders of magnitude lower. This study reports batch mode adsorption of anionic (2,4-D, C0 100 μg/L) and neutral (simazine [SZN], C0 1.5 μg/L) herbicides from surface water containing dissolved organic matter at 4 mg/L total organic carbon concentration. Enhanced adsorption was observed by biochars generated from updraft gasifiers under conditions of simultaneous co-pyrolysis thermal air activation (CPTA). 2,4-D adsorption by ≥850°C CPTA biochars was more than 10 times greater on a mass basis compared with biochars generated from a conventional anoxic pyrolysis (CAP) reactor and was equivalent to AC reference adsorbents on a surface area normalized basis. Biochars generated at ≥850°C under CPTA conditions had similar micropore surface area to CAP biochars (∼330 m2/g) but about 2.5 times the mesopore surface area (∼110 m2/g CPTA, ∼40 m2/g CAP), suggestive of increased pore accessibility generated by thermochemical widening of pores and/or removal of pyrolysis tars by CPTA. 2,4-D adsorption from surface water was shown to correlate strongly with biochar H:C molar ratio within but not between biochars grouped by CAP and CPTA generation conditions. Comparing adsorption of 2,4-D and SZN by biochars generated from CAP and CPTA conditions suggested that herbicide interaction with biochar surface functional groups through formation of charge-assisted H-bonds did not play a significant role in herbicide uptake from surface water. DA - 2019/6/1/ PY - 2019/6/1/ DO - 10.1089/ees.2018.0476 VL - 36 IS - 6 SP - 710-723 SN - 1557-9018 KW - 2 KW - 4-D KW - adsorption KW - aerobic pyrolysis KW - biochar KW - simazine ER - TY - JOUR TI - Ion mobility spectrometry and the omics: Distinguishing isomers, molecular classes and contaminant ions in complex samples AU - Burnum-Johnson, Kristin E. AU - Zheng, Xueyun AU - Dodds, James N. AU - Ash, Jeremy AU - Fourches, Denis AU - Nicora, Carrie D. AU - Wendler, Jason P. AU - Metz, Thomas O. AU - Waters, Katrina M. AU - Jansson, Janet K. AU - Smith, Richard D. AU - Baker, Erin S. T2 - TRAC-TRENDS IN ANALYTICAL CHEMISTRY AB - Ion mobility spectrometry (IMS) is a widely used analytical technique providing rapid gas phase separations. IMS alone is useful, but its coupling with mass spectrometry (IMS-MS) and various front-end separation techniques has greatly increased the molecular information achievable from different omic analyses. IMS-MS analyses are specifically gaining attention for improving metabolomic, lipidomic, glycomic, proteomic and exposomic analyses by increasing measurement sensitivity (e.g. S/N ratio), lowering the detection limit, and amplifying peak capacity. Numerous studies including national security-related analyses, disease screenings and environmental evaluations are illustrating that IMS-MS is able to extract information not possible with MS alone. Furthermore, IMS-MS has shown great utility in salvaging molecular information for low abundance molecules of interest when high concentration contaminant ions are present in the sample by reducing detector suppression. This review highlights how IMS-MS is currently being used in omic analyses to distinguish structurally similar molecules, isomers, molecular classes and contaminant ions. DA - 2019/7// PY - 2019/7// DO - 10.1016/j.trac.2019.04.022 VL - 116 SP - 292-299 SN - 1879-3142 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85065908529&partnerID=MN8TOARS KW - Ion mobility spectrometry KW - Mass spectrometry KW - Omics KW - Proteomics KW - Lipidomics KW - Metabolomics KW - Glycomics KW - Exposomics ER - TY - JOUR TI - Inappropriate Citation of Vaccine Article. T2 - The Journal of infectious diseases DA - 2019/6/3/ PY - 2019/6/3/ DO - 10.1093/infdis/jiz287 UR - https://doi.org/10.1093/infdis/jiz287 ER - TY - JOUR TI - Animal production, insecticide use and self-reported symptoms and diagnoses of COPD, including chronic bronchitis, in the Agricultural Health Study AU - Rinsky, Jessica L. AU - Richardson, David B. AU - Kreiss, Kathleen AU - Nylander-French, Leena AU - Freeman, Laura E. Beane AU - London, Stephanie J. AU - Henneberger, Paul K. AU - Hoppin, Jane A. T2 - ENVIRONMENT INTERNATIONAL AB - Occupational exposure to animal production is associated with chronic bronchitis symptoms; however, few studies consider associations with chronic obstructive pulmonary disease (COPD). We estimated associations between animal production activities and prevalence of self-reported COPD among farmers in the Agricultural Health Study.During a 2005-2010 interview, farmers self-reported information about: their operations (i.e., size, type, number of animals, insecticide use), respiratory symptoms, and COPD diagnoses (i.e., COPD, chronic bronchitis, emphysema). Operations were classified as small or medium/large based on regulatory definitions. Farmers were classified as having a COPD diagnosis, chronic bronchitis symptoms (cough and phlegm for ≥3 months during 2 consecutive years), or both. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).Of 22,491 participating farmers (median age: 59 years), 922 (4%) reported a COPD diagnosis only, 254 (1%) reported a diagnosis and symptoms, and 962 (4%) reported symptoms only. Compared to raising no commercial animals, raising animals on a medium/large operation was positively associated with chronic bronchitis symptoms with (OR: 1.59; 95% CI: 1.16, 2.18) and without a diagnosis (OR: 1.69; 95% CI: 1.42, 2.01). Ever use of multiple organophosphates, carbaryl, lindane, and permethrin were positively associated with chronic bronchitis symptoms.Animal production work, including insecticide use, was positively associated with chronic bronchitis symptoms; but not consistently with COPD diagnosis alone. Our results support the need for further investigation into the role of animal production-related exposures in the etiology of COPD and better respiratory protection for agricultural workers. DA - 2019/6// PY - 2019/6// DO - 10.1016/j.envint.2019.02.049 VL - 127 SP - 764-772 SN - 1873-6750 KW - Epidemiology KW - Occupational health KW - Environmental health KW - Pesticide ER - TY - JOUR TI - Does Granular Activated Carbon with Chlorination Produce Safer Drinking Water? From Disinfection Byproducts and Total Organic Halogen to Calculated Toxicity AU - Cuthbertson, Amy A. AU - Kimura, Susana Y. AU - Liberatore, Hannah K. AU - Summers, R. Scott AU - Knappe, Detlef R. U. AU - Stanford, Benjamin D. AU - Maness, J. Clark AU - Mulhern, Riley E. AU - Selbes, Meric AU - Richardson, Susan D. T2 - ENVIRONMENTAL SCIENCE & TECHNOLOGY DA - 2019/// PY - 2019/// DO - 10.1021/acs.est.9600023 VL - 53 IS - 10 SP - 5987-5999 ER - TY - JOUR TI - Maternal vitamin D deficiency and developmental origins of health and disease (DOHaD) AU - Ideraabdullah, Folami Y. AU - Belenchia, Anthony M. AU - Rosenfeld, Cheryl S. AU - Kullman, Seth W. AU - Knuth, Megan AU - Mahapatra, Debabrata AU - Bereman, Michael AU - Levinlo, Edward D. AU - Peterson, Catherine A. T2 - JOURNAL OF ENDOCRINOLOGY AB - Vitamin D is an essential nutrient that is metabolized in the body to generate an active metabolite (1,25(OH) 2 D) with hormone-like activity and highly diverse roles in cellular function. Vitamin D deficiency (VDD) is a prevalent but easily preventable nutritional disturbance. Emerging evidence demonstrates the importance of sufficient vitamin D concentrations during fetal life with deficiencies leading to long-term effects into adulthood. Here, we provide a detailed review and perspective of evidence for the role of maternal VDD in offspring long-term health, particularly as it relates to developmental origins of health and disease (DOHaD). We focus on the roles in neurobehavioral and cardiometabolic disorders in humans and highlight recent findings from zebrafish and rodent models that probe potential mechanisms linking early life VDD to later life health outcomes. Moreover, we explore evidence implicating epigenetic mechanisms as a mediator of this link. Gaps in our current understanding of how maternal VDD might result in deleterious offspring outcomes later in life are also addressed. DA - 2019/5// PY - 2019/5// DO - 10.1530/JOE-18-0541 VL - 241 IS - 2 SP - R65-R80 SN - 1479-6805 KW - vitamin D deficiency KW - DOHAD KW - metabolic disorders KW - autism KW - neurobehavioral disorders KW - animal models ER - TY - JOUR TI - Systematic determination of the relationship between nanoparticle core diameter and toxicity for a series of structurally analogous gold nanoparticles in zebrafish AU - Truong, Lisa AU - Zaikova, Tatiana AU - Baldock, Brandi L AU - Balik-Meisner, Michele AU - To, Kimberly AU - Reif, David M AU - Kennedy, Zachary C AU - Hutchison, James E AU - Tanguay, Robert L T2 - Nanotoxicology AB - Predictive models for the impact of nanomaterials on biological systems remain elusive. Although there is agreement that physicochemical properties (particle diameter, shape, surface chemistry, and core material) influence toxicity, there are limited and often contradictory, data relating structure to toxicity, even for core diameter. Given the importance of size in determining nanoscale properties, we aimed to address this data gap by examining the biological effects of a defined series of gold nanoparticles (AuNPs) on zebrafish embryos. Five AuNPs samples with narrowly spaced core diameters (0.8–5.8 nm) were synthesized and functionalized with positively charged N,N,N-trimethylammonium ethanethiol (TMAT) ligands. We assessed the bioactivity of these NPs in a high-throughput developmental zebrafish assay at eight concentrations (0.5–50 µg/mL) and observed core diameter-dependent bioactivity. The smaller diameter AuNPs were the most toxic when expressing exposures based on an equal mass. However, when expressing exposures based on total surface area, toxicity was independent of the core diameter. When holding the number of nanoparticles per volume constant (at 6.71 × 1013/mL) in the exposure medium across AuNPs diameters, only the 5.8 nm AuNPs exhibited toxic effects. Under these exposure conditions, the uptake of AuNPs in zebrafish was only weakly associated with core diameter, suggesting that differential uptake of TMAT-AuNPs was not responsible for toxicity associated with the 5.8 nm core diameter. Our results indicate that larger NPs may be the most toxic on a per particle basis and highlight the importance of using particle number and surface area, in addition to mass, when evaluating the size-dependent bioactivity of NPs. DA - 2019/// PY - 2019/// DO - 10.1080/17435390.2019.1592259 VL - 4 SP - 1—15 UR - https://doi.org/10.1080/17435390.2019.1592259 KW - Size-dependency KW - gold nanoparticles KW - zebrafish KW - uptake KW - ligands ER - TY - JOUR TI - Predicting Ion Mobility Collision Cross-Sections Using a Deep Neural Network: DeepCCS AU - Plante, Pier-Luc AU - Francovic-Fontaine, Elina AU - May, Jody C. AU - McLean, John A. AU - Baker, Erin S. AU - Laviolette, Francois AU - Marchand, Mario AU - Corbeil, Jacques T2 - ANALYTICAL CHEMISTRY AB - Untargeted metabolomic measurements using mass spectrometry are a powerful tool for uncovering new small molecules with environmental and biological importance. The small molecule identification step, however, still remains an enormous challenge due to fragmentation difficulties or unspecific fragment ion information. Current methods to address this challenge are often dependent on databases or require the use of nuclear magnetic resonance (NMR), which have their own difficulties. The use of the gas-phase collision cross section (CCS) values obtained from ion mobility spectrometry (IMS) measurements were recently demonstrated to reduce the number of false positive metabolite identifications. While promising, the amount of empirical CCS information currently available is limited, thus predictive CCS methods need to be developed. In this article, we expand upon current experimental IMS capabilities by predicting the CCS values using a deep learning algorithm. We successfully developed and trained a prediction model for CCS values requiring only information about a compound's SMILES notation and ion type. The use of data from five different laboratories using different instruments allowed the algorithm to be trained and tested on more than 2400 molecules. The resulting CCS predictions were found to achieve a coefficient of determination of 0.97 and median relative error of 2.7% for a wide range of molecules. Furthermore, the method requires only a small amount of processing power to predict CCS values. Considering the performance, time, and resources necessary, as well as its applicability to a variety of molecules, this model was able to outperform all currently available CCS prediction algorithms. DA - 2019/4/16/ PY - 2019/4/16/ DO - 10.1021/acs.analchem.8b05821 VL - 91 IS - 8 SP - 5191-5199 SN - 1520-6882 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85064178745&partnerID=MN8TOARS ER - TY - JOUR TI - An algorithm for quantitatively estimating non-occupational pesticide exposure intensity for spouses in the Agricultural Health Study AU - Deziel, Nicole C. AU - Freeman, Laura E. Beane AU - Hoppin, Jane A. AU - Thomas, Kent AU - Lerro, Catherine C. AU - Jones, Rena R. AU - Hines, Cynthia J. AU - Blair, Aaron AU - Graubard, Barry I AU - Lubin, Jay H. AU - Sandler, Dale P. AU - Chen, Honglei AU - Andreotti, Gabriella AU - Alavanja, Michael C. AU - Friesen, Melissa C. T2 - JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY AB - Residents of agricultural areas experience pesticide exposures from sources other than direct agricultural work. We developed a quantitative, active ingredient-specific algorithm for cumulative (adult, married lifetime) non-occupational pesticide exposure intensity for spouses of farmers who applied pesticides in the Agricultural Health Study (AHS). The algorithm addressed three exposure pathways: take-home, agricultural drift, and residential pesticide use. Pathway-specific equations combined (i) weights derived from previous meta-analyses of published pesticide exposure data and (ii) information from the questionnaire on frequency and duration of pesticide use by applicators, home proximity to treated fields, residential pesticide usage (e.g., termite treatments), and spouse’s off-farm employment (proxy for time at home). The residential use equation also incorporated a published probability matrix that documented the likelihood active ingredients were used in home pest treatment products. We illustrate use of these equations by calculating exposure intensities for the insecticide chlorpyrifos and herbicide atrazine for 19,959 spouses. Non-zero estimates for ≥1 pathway were found for 78% and 77% of spouses for chlorpyrifos and atrazine, respectively. Variability in exposed spouses’ intensity estimates was observed for both pesticides, with 75th to 25th percentile ratios ranging from 7.1 to 7.3 for take-home, 6.5 to 8.5 for drift, 2.4 to 2.8 for residential use, and 3.8 to 7.0 for the summed pathways. Take-home and drift estimates were highly correlated (≥0.98), but were not correlated with residential use (0.01‒0.02). This algorithm represents an important advancement in quantifying non-occupational pesticide relative exposure differences and will facilitate improved etiologic analyses in the AHS spouses. The algorithm could be adapted to studies with similar information. DA - 2019/4// PY - 2019/4// DO - 10.1038/s41370-018-0088-z VL - 29 IS - 3 SP - 344-357 SN - 1559-064X ER - TY - JOUR TI - Evidence for Aryl hydrocarbon Receptor-Mediated Inhibition of Osteoblast Differentiation in Human Mesenchymal Stem Cells AU - Watson, AtLee T. D. AU - Nordberg, Rachel C. AU - Loboa, Elizabeth G. AU - Kullman, Seth W. T2 - TOXICOLOGICAL SCIENCES AB - Multipotent mesenchymal stem cells (MSCs) maintain the ability to differentiate into adipogenic, chondrogenic, or osteogenic cell lineages. There is increasing concern that exposure to environmental agents such as aryl hydrocarbon receptor (AhR) ligands, may perturb the osteogenic pathways responsible for normal bone formation. The objective of the current study was to evaluate the potential of the prototypic AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to disrupt osteogenic differentiation of human bone-derived MSCs (hBMSCs) in vitro. Primary hBMSCs from three donors were exposed to 10 nM TCDD and differentiation was interrogated using select histological, biochemical, and transcriptional markers of osteogenesis. Exposure to 10 nM TCDD resulted in an overall consistent attenuation of alkaline phosphatase (ALP) activity and matrix mineralization at terminal stages of differentiation in primary hBMSCs. At the transcriptional level, the transcriptional regulator DLX5 and additional osteogenic markers (ALP, OPN, and IBSP) displayed attenuated expression; conversely, FGF9 and FGF18 were consistently upregulated in each donor. Expression of stem cell potency markers SOX2, NANOG, and SALL4 decreased in the osteogenic controls, whereas expression in TCDD-treated cells resembled that of undifferentiated cells. Coexposure with the AhR antagonist GNF351 blocked TCDD-mediated attenuation of matrix mineralization, and either fully or partially rescued expression of genes associated with osteogenic regulation, extracellular matrix, and/or maintenance of multipotency. Thus, experimental evidence from this study suggests that AhR transactivation likely attenuates osteoblast differentiation in multipotent hBMSCs. This study also underscores the use of primary human MSCs to evaluate osteoinductive or osteotoxic potential of chemical and pharmacologic agents in vitro. DA - 2019/1// PY - 2019/1// DO - 10.1093/toxsci/kfy225 VL - 167 IS - 1 SP - 145-156 SN - 1096-0929 KW - aryl hydrocarbon receptor KW - 2,3,7,8-tetrachlorodibenzo-p-dioxin KW - TCDD KW - mesenchymal stem cell KW - osteoblast differentiation KW - skeletal toxicity KW - bone toxicity ER - TY - JOUR TI - Associations between access to healthcare, environmental quality, and end-stage renal disease survival time: Proportional-hazards models of over 1,000,000 people over 14 years AU - Kosnik, Marissa B. AU - Reif, David M. AU - Lobdell, Danelle T. AU - Astell-Burt, Thomas AU - Feng, Xiaoqi AU - Hader, John D. AU - Hoppin, Jane A. T2 - PLOS ONE AB - Prevalence of end-stage renal disease (ESRD) in the US increased by 74% from 2000 to 2013. To investigate the role of the broader environment on ESRD survival time, we evaluated average distance to the nearest hospital by county (as a surrogate for access to healthcare) and the Environmental Quality Index (EQI), an aggregate measure of ambient environmental quality composed of five domains (air, water, land, built, and sociodemographic), at the county level across the US. Associations between average hospital distance, EQI, and survival time for 1,092,281 people diagnosed with ESRD between 2000 and 2013 (age 18+, without changes in county residence) from the US Renal Data System were evaluated using proportional-hazards models adjusting for gender, race, age at first ESRD service date, BMI, alcohol and tobacco use, and rurality. The models compared the average distance to the nearest hospital (<10, 10–20, >20 miles) and overall EQI percentiles [0–5), [5–20), [20–40), [40–60), [60–80), [80–95), and [95–100], where lower percentiles are interpreted as better EQI. In the full, non-stratified model with both distance and EQI, there was increased survival for patients over 20 miles from a hospital compared to those under 10 miles from a hospital (hazard ratio = 1.14, 95% confidence interval = 1.12–1.15) and no consistent direction of association across EQI strata. In the full model stratified by average hospital distance, under 10 miles from a hospital had increased survival in the worst EQI strata (median survival 3.0 vs. 3.5 years for best vs. worst EQI, respectively), however for people over 20 miles from a hospital, median survival was higher in the best (4.2 years) vs worst (3.4 years) EQI. This association held across different rural/urban categories and age groups. These results demonstrate the importance of considering multiple factors when studying ESRD survival and future efforts should consider additional components of the broader environment. DA - 2019/3/21/ PY - 2019/3/21/ DO - 10.1371/journal.pone.0214094 VL - 14 IS - 3 SP - SN - 1932-6203 UR - https://doi.org/10.1371/journal.pone.0214094 ER - TY - JOUR TI - The Comparative Toxicogenomics Database: update 2019 AU - Davis, Allan Peter AU - Grondin, Cynthia J. AU - Johnson, Robin J. AU - Sciaky, Daniela AU - McMorran, Roy AU - Wiegers, Jolene AU - Wiegers, Thomas C. AU - Mattingly, Carolyn J. T2 - NUCLEIC ACIDS RESEARCH AB - The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) is a premier public resource for literature-based, manually curated associations between chemicals, gene products, phenotypes, diseases, and environmental exposures. In this biennial update, we present our new chemical–phenotype module that codes chemical-induced effects on phenotypes, curated using controlled vocabularies for chemicals, phenotypes, taxa, and anatomical descriptors; this module provides unique opportunities to explore cellular and system-level phenotypes of the pre-disease state and allows users to construct predictive adverse outcome pathways (linking chemical–gene molecular initiating events with phenotypic key events, diseases, and population-level health outcomes). We also report a 46% increase in CTD manually curated content, which when integrated with other datasets yields more than 38 million toxicogenomic relationships. We describe new querying and display features for our enhanced chemical–exposure science module, providing greater scope of content and utility. As well, we discuss an updated MEDIC disease vocabulary with over 1700 new terms and accession identifiers. To accommodate these increases in data content and functionality, CTD has upgraded its computational infrastructure. These updates continue to improve CTD and help inform new testable hypotheses about the etiology and mechanisms underlying environmentally influenced diseases. DA - 2019/1/8/ PY - 2019/1/8/ DO - 10.1093/nar/gky868 VL - 47 IS - D1 SP - D948-D954 SN - 1362-4962 ER - TY - JOUR TI - Improving understanding of carbon storage in wood in landfills: Evidence from reactor studies AU - Ximenes, Fabiano A. AU - Bjordal, Charlotte AU - Kathuria, Amrit AU - Barlaz, Morton A. AU - Cowie, Annette L. T2 - WASTE MANAGEMENT AB - Approximately 1.5 million tonnes (Mt) of wood waste are disposed of in Australian landfills annually. Recent studies have suggested that anaerobic decay levels of wood in landfills are low, although knowledge of the decay of individual wood species is limited. The objective of this study was to establish the extent of carbon loss for wood species of commercial importance in Australia including radiata pine, blackbutt, spotted gum and mountain ash. Experiments were conducted under laboratory conditions designed to simulate optimal anaerobic biodegradation in a landfill. Bacterial degradation, identified by both light microscopy and electron microscopy, occurred to a varying degree in mountain ash and spotted gum wood. Fungal decay was not observed in any wood samples. Mountain ash, the species with the highest methane yield (20.9 mL CH4/g) also had the highest holocellulose content and the lowest acid-insoluble lignin and extractive content. As the decay levels for untreated radiata pine were very low, it was not possible to determine whether impregnation of radiata pine with chemical preservatives had any impact on decay. Carbon losses estimated from gas generation were below 5% for all species tested. Carbon losses as estimated by gas generation were lower than those derived by mass balance in most reactors, suggesting that mass loss does not necessarily equate to carbon emissions. There was no statistical difference between decay of blackbutt derived from plantation and older, natural forests. Addition of paper as an easily digestible feedstock did not increase carbon loss for the two wood species tested and the presence of radiata pine had an inhibitory effect on copy paper decay. Although differences between some of the wood types were found to be statistically significant, these differences were detected for wood with carbon losses that did not exceed 5%. The suggested factor for carbon loss for wood in landfills in Australia is 1.4%. This study confirms that disposal of wood in landfills in Australia results in long-term storage of carbon, with only minimal conversion of carbon to gaseous end products. DA - 2019/2/15/ PY - 2019/2/15/ DO - 10.1016/j.wasman.2019.01.004 VL - 85 SP - 341-350 SN - 0956-053X KW - Wood KW - Carbon KW - Landfill KW - Methane KW - Decay KW - Bacteria ER - TY - JOUR TI - Identifying individual risk rare variants using protein structure guided local tests (POINT) AU - West, Rachel Marceau AU - Lu, Wenbin AU - Rotroff, Daniel M. AU - Kuenemann, Melaine A. AU - Chang, Sheng-Mao AU - Wu, Michael C. AU - Wagner, Michael J. AU - Buse, John B. AU - Motsinger-Reif, Alison A. AU - Fourches, Denis AU - Tzeng, Jung-Ying T2 - PLOS COMPUTATIONAL BIOLOGY AB - Rare variants are of increasing interest to genetic association studies because of their etiological contributions to human complex diseases. Due to the rarity of the mutant events, rare variants are routinely analyzed on an aggregate level. While aggregation analyses improve the detection of global-level signal, they are not able to pinpoint causal variants within a variant set. To perform inference on a localized level, additional information, e.g., biological annotation, is often needed to boost the information content of a rare variant. Following the observation that important variants are likely to cluster together on functional domains, we propose a protein structure guided local test (POINT) to provide variant-specific association information using structure-guided aggregation of signal. Constructed under a kernel machine framework, POINT performs local association testing by borrowing information from neighboring variants in the 3-dimensional protein space in a data-adaptive fashion. Besides merely providing a list of promising variants, POINT assigns each variant a p-value to permit variant ranking and prioritization. We assess the selection performance of POINT using simulations and illustrate how it can be used to prioritize individual rare variants in PCSK9, ANGPTL4 and CETP in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial data. DA - 2019/2// PY - 2019/2// DO - 10.1371/journal.pcbi.1006722 VL - 15 IS - 2 SP - SN - 1553-7358 ER - TY - JOUR TI - CAD1 and CCR2 protein complex formation in monolignol biosynthesis in Populus trichocarpa AU - Yan, Xiaojing AU - Liu, Jie AU - Kim, Hoon AU - Liu, Baoguang AU - Huang, Xiong AU - Yang, Zhichang AU - Lin, Ying-Chung Jimmy AU - Chen, Hao AU - Yang, Chenmin AU - Wang, Jack P. AU - Muddiman, David C. AU - Ralph, John AU - Sederoff, Ronald R. AU - Li, Quanzi AU - Chiang, Vincent L. T2 - NEW PHYTOLOGIST AB - Lignin is the major phenolic polymer in plant secondary cell walls and is polymerized from monomeric subunits, the monolignols. Eleven enzyme families are implicated in monolignol biosynthesis. Here, we studied the functions of members of the cinnamyl alcohol dehydrogenase (CAD) and cinnamoyl-CoA reductase (CCR) families in wood formation in Populus trichocarpa, including the regulatory effects of their transcripts and protein activities on monolignol biosynthesis. Enzyme activity assays from stem-differentiating xylem (SDX) proteins showed that RNAi suppression of PtrCAD1 in P. trichocarpa transgenics caused a reduction in SDX CCR activity. RNAi suppression of PtrCCR2, the only CCR member highly expressed in SDX, caused a reciprocal reduction in SDX protein CAD activities. The enzyme assays of mixed and coexpressed recombinant proteins supported physical interactions between PtrCAD1 and PtrCCR2. Biomolecular fluorescence complementation and pull-down/co-immunoprecipitation experiments supported a hypothesis of PtrCAD1/PtrCCR2 heterodimer formation. These results provide evidence for the formation of PtrCAD1/PtrCCR2 protein complexes in monolignol biosynthesis in planta. DA - 2019/4// PY - 2019/4// DO - 10.1111/nph.15505 VL - 222 IS - 1 SP - 244-260 SN - 1469-8137 KW - co-immunoprecipitation KW - enzyme activity KW - monolignol biosynthetic pathway KW - nuclear magnetic resonance (NMR) KW - Populus trichocarpa KW - stem-differentiating xylem protein ER - TY - JOUR TI - Solid Waste Management Policy Implications on Waste Process Choices and Systemwide Cost and Greenhouse Gas Performance AU - Jaunich, Megan K. AU - Levis, James W. AU - DeCarolis, Joseph F. AU - Barlaz, Morton A. AU - Ranjithan, S. Ranji T2 - ENVIRONMENTAL SCIENCE & TECHNOLOGY AB - Solid waste management (SWM) is a key function of local government and is critical to protecting human health and the environment. Development of effective SWM strategies should consider comprehensive SWM process choices and policy implications on system-level cost and environmental performance. This analysis evaluated cost and select environmental implications of SWM policies for Wake County, North Carolina using a life-cycle approach. A county-specific data set and scenarios were developed to evaluate alternatives for residential municipal SWM, which included combinations of a mixed waste material recovery facility (MRF), anaerobic digestion, and waste-to-energy combustion in addition to existing SWM infrastructure (composting, landfilling, single stream recycling). Multiple landfill diversion and budget levels were considered for each scenario. At maximum diversion, the greenhouse gas (GHG) mitigation costs ranged from 30 to 900 $/MTCO2e; the lower values were when a mixed waste MRF was used, and the higher values when anaerobic digestion was used. Utilization of the mixed waste MRF was sensitive to the efficiency of material separation and operating cost. Maintaining the current separate collection scheme limited the potential for cost and GHG reductions. Municipalities seeking to cost-effectively increase landfill diversion while reducing GHGs should consider waste-to-energy, mixed waste separation, and changes to collection. DA - 2019/2/19/ PY - 2019/2/19/ DO - 10.1021/acs.est.8b04589 VL - 53 IS - 4 SP - 1766-1775 SN - 1520-5851 ER - TY - JOUR TI - Binding of peanut allergen Ara h 2 with Vaccinium fruit polyphenols AU - Plundrich, Nathalie J. AU - Cook, Bethany T. AU - Maleki, Soheila J. AU - Fourches, Denis AU - Lila, Mary Ann T2 - FOOD CHEMISTRY AB - The potential for 42 different polyphenols found in Vaccinium fruits to bind to peanut allergen Ara h 2 and inhibit IgE binding epitopes was investigated using cheminformatics techniques. Out of 12 predicted binders, delphinidin-3-glucoside, cyanidin-3-glucoside, procyanidin C1, and chlorogenic acid were further evaluated in vitro. Circular dichroism, UV-Vis spectroscopy, and immunoblotting determined their capacity to (i) bind to Ara h 2, (ii) induce protein secondary structural changes, and (iii) inhibit IgE binding epitopes. UV-Vis spectroscopy clearly indicated that procyanidin C1 and chlorogenic acid interacted with Ara h 2, and circular dichroism results suggested that interactions with these polyphenols resulted in changes to Ara h 2 secondary structures. Immunoblotting showed that procyanidin C1 and chlorogenic acid bound to Ara h 2 significantly decreased the IgE binding capacity by 37% and 50%, respectively. These results suggest that certain polyphenols can inhibit IgE recognition of Ara h 2 by obstructing linear IgE epitopes. DA - 2019/6/30/ PY - 2019/6/30/ DO - 10.1016/j.foodchem.2019.01.081 VL - 284 SP - 287-295 SN - 1873-7072 KW - Ara h 2 KW - Molecular docking KW - Polyphenol KW - IgE binding KW - Circular dichroism (CD) KW - Food allergy ER - TY - JOUR TI - Discriminating normal regions within cancerous hen ovarian tissue using multivariate hyperspectral image analysis AU - Lakeh, Mahsa Akbari AU - Tu, Anqi AU - Muddiman, David C. AU - Abdollahi, Hamid T2 - RAPID COMMUNICATIONS IN MASS SPECTROMETRY AB - Identification of subregions under different pathological conditions on cancerous tissue is of great significance for understanding cancer progression and metastasis. Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry (IR-MALDESI-MS) can be potentially used for diagnostic purposes since it can monitor spatial distribution and abundance of metabolites and lipids in biological tissues. However, the large size and high dimensionality of hyperspectral data make analysis and interpretation challenging. To overcome these barriers, multivariate methods were applied to IR-MALDESI data for the first time, aiming at efficiently resolving mass spectral images, from which these results were then used to identify normal regions within cancerous tissue.Molecular profiles of healthy and cancerous hen ovary tissues were generated by IR-MALDESI-MS. Principal component analysis (PCA) combined with color-coding built a single tissue image which summarizes the high-dimensional data features. Pixels with similar color indicated similar composition. PCA results from healthy tissue were further used to test each pixel in cancerous tissue to determine if it is healthy. Multivariate curve resolution-alternating least squares (MCR-ALS) was used to obtain major spatial features existing in ovary tissues, and group molecules with the same distribution patterns simultaneously.PCA as the predominating dimensionality reduction approach captured over 90% spectral variances by the first three PCs. The PCA images show the cancerous tissue is more chemically heterogeneous than healthy tissue, where at least four regions with different m/z profiles can be differentiated. PCA modeling assigns top regions of cancerous tissue as healthy-like. MCR-ALS extracted three and four major compounds from healthy and cancerous tissue, respectively. Evaluating similarities of resolved spectra uncovered the chemical components that were distinct in some regions on cancerous tissue, serving as a supplementary way to differentiate healthy and cancerous regions.Two unsupervised chemometric methods including PCA and MCR-ALS were applied for resolving and visualizing IR-MALDESI-MS data acquired from hen ovary tissues, improving the interpretation of mass spectrometry imaging results. Then possible normal regions were differentiated from cancerous tissue sections. No prior knowledge is required using either chemometric method, so our approach is readily suitable for unstained tissue samples, which allows one to reveal the molecular events happening during disease progression. DA - 2019/2/28/ PY - 2019/2/28/ DO - 10.1002/rcm.8362 VL - 33 IS - 4 SP - 381-391 SN - 1097-0231 ER - TY - JOUR TI - Characterizing sources of variability in zebrafish embryo screening protocols AU - Hamm, Jon 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 - Tai, 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 - 2019/// PY - 2019/// DO - 10.14573/altex.1804162 VL - 36 IS - 1 SP - 103–120 SN - 1868-596X UR - http://dx.doi.org/10.14573/altex.1804162 ER - TY - JOUR TI - Elevated metabolites of acetaminophen in cord blood of children with obesity AU - Sorrow, P. AU - Maguire, R. AU - Murphy, S. K. AU - Belcher, S. M. AU - Hoyo, C. T2 - PEDIATRIC OBESITY AB - High-throughput metabolomics has been used cross-sectionally to evaluate differential metabolic profiles associated with human obesity.This study longitudinally assessed the cord blood metabolome to explore if metabolic signatures of obesity at age 3-5 are apparent at birth.In a nested case-control design, metabolomics analysis was performed on umbilical cord blood of 25 children who developed obesity by age 3-5 years, compared with 25 sex-matched non-obese children enrolled as part of an ongoing birth cohort. Logistic regression models were used to identify significant metabolites, adjusting for maternal pre-pregnancy obesity.Children who had obesity by age 3-5 years had elevated levels of medium and long chain fatty acids including stearate, oleate and palmitate at birth. Children with obesity were also more likely to have elevated levels of acetaminophen metabolites at birth, specifically: 3-(N-acetyl-L-cystein-S-yl) acetaminophen, 2-hydroxyacetaminophen sulfate, 2-methoxyacetaminophen glucuronide and p-acetamidophenyl glucuronide.Although the observed increases in lipids are consistent with previous metabolomic studies of obesity, this study is the first to report associations between acetaminophen metabolites and obesity in children; however, we lack mechanistic insights for this link. Larger human studies with longer follow-up and laboratory-controlled animal experiments are needed to clarify associations. DA - 2019/1// PY - 2019/1// DO - 10.1111/ijpo.12465 VL - 14 IS - 1 SP - SN - 2047-6302 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85053785805&partnerID=MN8TOARS KW - Acetaminophen KW - children KW - metabolomics KW - obesity ER - TY - JOUR TI - Are sulfate effects in the mayfly Neocloeon triangulifer driven by the cost of ion regulation? AU - Buchwalter, David AU - Scheibener, Shane AU - Chou, Hsuan AU - Soucek, David AU - Elphick, James T2 - PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES AB - Elevated major ion concentrations in streams are commonly observed as a consequence of resource extraction, de-icing and other anthropogenic activities. Ecologists report biodiversity losses associated with increasing salinity, with mayflies typically being highly responsive to increases of different major ions. In this study, we evaluated the performance of the mayfly Neocloeon triangulifer reared for its entire larval phase in a gradient of sulfate concentrations. Two natural waters were amended with SO 4 as a blend of CaSO 4 and MgSO 4 and exposures ranged from 5 to 1500 mg l –1 SO 4. Survival (per cent successful emergence to the subimago stage) was significantly reduced at the highest SO 4 concentration in both waters, while development was significantly delayed at 667 mg l −1 SO 4 . Final sub-adult body weights were consistent across treatments, except at the highest treatment concentration. Despite evidence for sulfate uptake rates increasing with exposure concentrations and not being saturated at even extremely high SO 4 concentrations, total body sulfur changed little in subimagos. Together, these results suggest that elevated SO 4 imposes an energetic demand associated with maintaining homeostasis that is manifested primarily as reduced growth rates and associated developmental delays. We identified two genes related to sulfate transport in N. triangulifer . This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’. DA - 2019/1/21/ PY - 2019/1/21/ DO - 10.1098/rstb.2018.0013 VL - 374 IS - 1764 SP - SN - 1471-2970 KW - salinity stress KW - ion transport KW - mayfly KW - development KW - freshwater ecosystem ER - TY - JOUR TI - Discovery and quantification of bioactive peptides in fermented cucumber by direct analysis IR-MALDESI mass spectrometry and LC-QQQ-MS AU - Fideler, Jennifer AU - Johanningsmeier, Suzanne D. AU - Ekelof, Mans AU - Muddiman, David C. T2 - FOOD CHEMISTRY AB - Bioactive peptides have been identified in lactic acid bacteria fermented foods including cultured milk, sourdough, and cured meats; however, their presence has not been investigated in fermented vegetables. In this study, infrared, matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry (MS) was employed to identify bioactive peptides in fermented cucumber. Natural and starter culture fermented cucumbers were prepared in triplicate in sodium chloride brines and compared to acidified cucumbers. Putative matches of known food-derived bioactive peptides were identified by direct analysis using IR-MALDESI-MS. Peptides were confirmed by IR-MALDESI MS/MS and quantified by LC-MS/MS. Three angiotensin converting enzyme (ACE) inhibitory peptides, IPP (0.42–0.49 mg/kg), LPP (0.30–0.33 mg/kg), and VPP (0.32–0.35 mg/kg) were formed in fermented cucumbers. A fourth ACE inhibitory peptide, KP (0.93–1.5 mg/kg), was enhanced 3–5 fold in fermented cucumbers compared with acidified cucumbers. This work demonstrates that lactic acid bacteria fermentation can enhance bioactive peptide content in vegetables. DA - 2019/1/15/ PY - 2019/1/15/ DO - 10.1016/j.foodchem.2018.07.187 VL - 271 SP - 715-723 SN - 1873-7072 KW - Lactic acid fermentation KW - ACE-inhibitory peptides KW - Isoleucine-proline-proline KW - Leucine-proline-proline KW - Valine-proline-proline KW - Vegetable composition ER -