TY - CONF TI - Characterization of atmospheric pressure rf discharges with aqueous plasma facing surfaces AU - Lindsay, A. AU - Byrns, B. AU - Knappe, D. AU - Shannon, S. AB - Summary form only given. Plasma modification of liquids has opened a broad range of new applications ranging from wound treatment to water purification to agricultural fertigation and herbicide. Two of the primary challenges facing systems designed to modify liquid chemistry through plasma treatment have been throughput and efficient introduction of liquid species in the active plasma region. In this presentation, we present novel pathways for both source scale up and liquid incorporation that can make plasma treatment of liquids more economically viable. C2 - 2015/// C3 - ICOPS/BEAMS 2014 - 41st IEEE International Conference on Plasma Science and the 20th International Conference on High-Power Particle Beams DA - 2015/// DO - 10.1109/PLASMA.2014.7012279 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84923050875&partnerID=MN8TOARS ER - TY - RPRT TI - Removal of perfluoroalkyl substances by PAC adsorption and anion exchange AU - Dudley, L.A. AU - Arevalo, E.C. AU - Knappe, D.R.U. A3 - Water Research Foundation DA - 2015/// PY - 2015/// M1 - 4344 M3 - Executive summary PB - Water Research Foundation SN - 4344 ER - TY - RPRT TI - Removal of volatile organic contaminants (VOCs) from drinking water via granular activated carbon treatment AU - Summers, R.S. AU - Kempisty, D. AU - Daugherty, T. AU - Knappe, D. A3 - Water Research Foundation DA - 2015/// PY - 2015/// M1 - 4440 M3 - Final report PB - Water Research Foundation SN - 4440 ER - TY - CONF TI - Developing Energy and Greenhouse Gas Emission Factors for Anaerobic Digestion in U.S. EPA's Waste Reduction Model AU - Renz, B. AU - Evans, C. AU - Barlaz, M.A. AU - Levis, J.W. AU - Kollar, T. AU - Boland, C. T2 - LCA XV C2 - 2015/// CY - Vancouver, BC DA - 2015/// PY - 2015/10// ER - TY - CONF TI - Methods to measure the hydrogen sulfide production potential of sulfate-containing wastes disposed in landfills AU - Sun, W.J. AU - Sun, M. AU - Barlaz, M.A. T2 - 15th International Waste Management and Landfill Symposium C2 - 2015/// CY - S. Margherita di Pula (CA), Italy DA - 2015/// PY - 2015/10/5/ ER - TY - CONF TI - A systematic evaluation of the costs and environmental impacts associated with future municipal solid waste management AU - Levis, J. AU - Barlaz, M. AU - DeCarolis, J. AU - Ranjithan, R. T2 - 5th International Waste Management and Landfill Symposium C2 - 2015/// CY - S. Margherita di Pula (CA), Italy DA - 2015/// PY - 2015/10/5/ ER - TY - JOUR TI - Response to the letter by Gallo D., et al AU - Belcher, S.M. T2 - Endocrinology DA - 2015/// PY - 2015/// DO - 10.1210/en.2015-1484 VL - 156 IS - 8 SP - L8-L9 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84938684568&partnerID=MN8TOARS ER - TY - JOUR TI - Non-monotonic dose-response relationships and endocrine disruptors: A qualitative method of assessment -No section- AU - Lagarde, F. AU - Beausoleil, C. AU - Belcher, S.M. AU - Belzunces, L.P. AU - Emond, C. AU - Guerbet, M. AU - Rousselle, C. T2 - Environmental Health: A Global Access Science Source AB - Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that report NMDR relationships with endocrine disruptors. Fifty-one experimental studies that investigated various effects associated with endocrine disruption elicited by many substances were selected. Scoring criteria were applied by adaptation of an approach previously used for identification of hormesis-type dose-response relationships. Out of the 148 NMDR relationships analyzed, 82 were categorized with this method as having a “moderate” to “high” level of plausibility for various effects. Numerous modes of action described in the literature can explain such phenomena. NMDR can arise from numerous molecular mechanisms such as opposing effects induced by multiple receptors differing by their affinity, receptor desensitization, negative feedback with increasing dose, or dose-dependent metabolism modulation. A stepwise decision tree was developed as a tool to standardize the analysis of NMDR relationships observed in the literature with the final aim to use these results in a Risk Assessment purpose. This decision tree was finally applied to studies focused on the effects of bisphenol A. DA - 2015/// PY - 2015/// DO - 10.1186/1476-069X-14-13 VL - 14 IS - 1 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84929008164&partnerID=MN8TOARS KW - Endocrine disruptors KW - NMDR KW - Non-monotonic KW - Dose-response KW - Risk assessment KW - Bisphenol A ER - TY - JOUR TI - Estrogen receptor-β up-regulates IGF1R expression and activity to inhibit apoptosis and increase growth of medulloblastoma AU - Cookman, C.J. AU - Belcher, S.M. T2 - Endocrinology AB - Medulloblastoma (Med) is the most common malignant brain tumor in children. The role of ESR2 [estrogen receptor (ER)-β] in promoting Med growth was comprehensively examined in three in vivo models and human cell lines. In a novel Med ERβ-null knockout model developed by crossing Esr2(-/-) mice with cerebellar granule cell precursor specific Ptch1 conditional knockout mice, the tumor growth rate was significantly decreased in males and females. The absence of Esr2 resulted in increased apoptosis, decreased B-cell lymphoma 2 (BCL2), and IGF-1 receptor (IGF1R) expression, and decreased levels of active MAPKs (ERK1/2) and protein kinase B (AKT). Treatment of Med in Ptch1(+/-) Trp53(-/-) mice with the antiestrogen chemotherapeutic drug Faslodex significantly increased symptom-free survival, which was associated with increased apoptosis and decreased BCL2 and IGF1R expression and signaling. Similar effects were also observed in nude mice bearing D283Med xenografts. In vitro studies in human D283Med cells metabolically stressed by glutamine withdrawal found that 17β-estradiol and the ERβ selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile dose dependently protected Med cells from caspase-3-dependent cell death. Those effects were associated with increased phosphorylation of IGF1R, long-term increases in ERK1/2 and AKT signaling, and increased expression of IGF-1, IGF1R, and BCL2. Results of pharmacological experiments revealed that the cytoprotective actions of estradiol were dependent on ERβ and IGF1R receptor tyrosine kinase activity and independent of ERα and G protein-coupled estrogen receptor 1 (G protein coupled receptor 30). The presented results demonstrate that estrogen promotes Med growth through ERβ-mediated increases in IGF1R expression and activity, which induce cytoprotective mechanisms that decrease apoptosis. DA - 2015/// PY - 2015/// DO - 10.1210/en.2015-1141 VL - 156 IS - 7 SP - 2395-2408 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84937605783&partnerID=MN8TOARS ER - TY - JOUR TI - Bisphenol a alters autonomic tone and extracellular matrix structure and induces sex-specific effects on cardiovascular function in male and female CD-1 mice AU - Belcher, S.M. AU - Gear, R.B. AU - Kendig, E.L. T2 - Endocrinology AB - The aim of this study was to determine whether bisphenol A (BPA) has adverse effects on cardiovascular functions in CD-1 mice and define sex-specific modes of BPA action in the heart. Dams and analyzed progeny were maintained on a defined diet containing BPA (0.03, 0.3, 3, 30, or 300 ppm) that resulted in BPA exposures from 4-5 to approximately 5000 μg/kg · d or a diet containing 17α-ethinyl estradiol (EE; ∼0.02, 0.2, and 0.15 μg/kg · d) as an oral bioavailable estrogen control. Assessment of electrocardiogram parameters using noninvasive methods found that ventricular functions in both male and female mice were not altered by either BPA or EE. However, exposure-related changes in the rates of ventricular contraction, suggestive of a shift in sympathovagal balance of heart rate control toward increased parasympathetic activity, were detected in males. Decreased systolic blood pressure was observed in males exposed to BPA above 5 μg/kg · d and in females from the highest BPA exposure group. Morphometric histological measures revealed sexually dimorphic changes in the composition of the cardiac collagen extracellular matrix, increases in fibrosis, and evidence of modest exposure-related remodeling. Experiments using the α-selective adrenergic agonist phenylephrine found that BPA enhanced reflex bradycardia in females, but not males, revealed that BPA and EE exposure sex specifically altered the sympathetic regulation of the baroreflex circuits. Increased sensitivity to the cardiotoxic effects of the β-adrenergic agonist isoproterenol was observed in BPA- and EE-exposed females. This effect was not observed in males, in which BPA or EE exposures were protective of isoproterenol-induced ischemic damage and hypertrophy. The results of RNA sequence analysis identified significant sex-specific changes in gene expression in response to BPA that were consistent with the observed exposure-related phenotypic changes in the collagenous and noncollagenous extracellular matrix, cardiac remodeling, altered autonomic responses, changes in ion channel and transporter functions, and altered glycolytic and lipid metabolism. DA - 2015/// PY - 2015/// DO - 10.1210/en.2014-1847 VL - 156 IS - 3 SP - 882-895 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84923884313&partnerID=MN8TOARS ER - TY - JOUR TI - Comprehensive characterization of the Published Kinase Inhibitor Set AU - Elkins, Jonathan M AU - Fedele, Vita AU - Szklarz, Marta AU - Abdul Azeez, Kamal R AU - Salah, Eidarus AU - Mikolajczyk, Jowita AU - Romanov, Sergei AU - Sepetov, Nikolai AU - Huang, Xi-Ping AU - Roth, Bryan L AU - Al Haj Zen, Ayman AU - Fourches, Denis AU - Muratov, Eugene AU - Tropsha, Alex AU - Morris, Joel AU - Teicher, Beverly A AU - Kunkel, Mark AU - Polley, Eric AU - Lackey, Karen E AU - Atkinson, Francis L AU - Overington, John P AU - Bamborough, Paul AU - Müller, Susanne AU - Price, Daniel J AU - Willson, Timothy M AU - Drewry, David H AU - Knapp, Stefan AU - Zuercher, William J T2 - Nature Biotechnology AB - Despite the success of protein kinase inhibitors as approved therapeutics, drug discovery has focused on a small subset of kinase targets. Here we provide a thorough characterization of the Published Kinase Inhibitor Set (PKIS), a set of 367 small-molecule ATP-competitive kinase inhibitors that was recently made freely available with the aim of expanding research in this field and as an experiment in open-source target validation. We screen the set in activity assays with 224 recombinant kinases and 24 G protein-coupled receptors and in cellular assays of cancer cell proliferation and angiogenesis. We identify chemical starting points for designing new chemical probes of orphan kinases and illustrate the utility of these leads by developing a selective inhibitor for the previously untargeted kinases LOK and SLK. Our cellular screens reveal compounds that modulate cancer cell growth and angiogenesis in vitro. These reagents and associated data illustrate an efficient way forward to increasing understanding of the historically untargeted kinome. DA - 2015/10/26/ PY - 2015/10/26/ DO - 10.1038/NBT.3374 VL - 34 IS - 1 SP - 95-103 J2 - Nat Biotechnol LA - en OP - SN - 1087-0156 1546-1696 UR - http://dx.doi.org/10.1038/NBT.3374 DB - Crossref ER - TY - JOUR TI - In Response : Conservation versus functional diversification of nuclear receptors: An academic perspective AU - Kullman, Seth W. T2 - Environmental Toxicology and Chemistry AB - Environmental Toxicology and ChemistryVolume 34, Issue 3 p. 463-465 ET&C Perspectives In Response: Conservation versus functional diversification of nuclear receptors: An academic perspective Seth W. Kullman, Seth W. Kullman North Carolina State University Raleigh, North Carolina, USASearch for more papers by this author Seth W. Kullman, Seth W. Kullman North Carolina State University Raleigh, North Carolina, USASearch for more papers by this author First published: 24 February 2015 https://doi.org/10.1002/etc.2832Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume34, Issue3March 2015Pages 463-465 RelatedInformation DA - 2015/2/24/ PY - 2015/2/24/ DO - 10.1002/ETC.2832 VL - 34 IS - 3 SP - 463-465 J2 - Environ Toxicol Chem LA - en OP - SN - 0730-7268 UR - http://dx.doi.org/10.1002/ETC.2832 DB - Crossref ER - TY - CHAP TI - Mass Spectrometry for Biomarker Development AU - Wu, C. AU - Liu, T. AU - Baker, E.S. AU - Rodland, K.D. AU - Smith, R.D. T2 - General Methods in Biomarker Research and their Applications A2 - Preedy, V.R. A2 - Patel, V.B. PY - 2015/// SP - 17–48 PB - Springer ER - TY - JOUR TI - New Master of Science program emphasizing Safety Pharmacology—Results to date AU - Matlib, Abdul AU - Belcher, Scott AU - Rapoport, Robert AU - Millard, Ron AU - Wang, Hong-Sheng AU - Maggio, John T2 - Journal of Pharmacological and Toxicological Methods DA - 2015/9// PY - 2015/9// DO - 10.1016/J.VASCN.2015.08.114 VL - 75 SP - 191-192 J2 - Journal of Pharmacological and Toxicological Methods LA - en OP - SN - 1056-8719 UR - http://dx.doi.org/10.1016/J.VASCN.2015.08.114 DB - Crossref ER - TY - JOUR TI - Effects of whole life exposure to Bisphenol A or 17α-ethinyl estradiol in uterus of nulligravida CD1 mice AU - Kendziorski, Jessica A. AU - Belcher, Scott M. T2 - Data in Brief AB - Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) with known estrogenic activity. Exposure to BPA in adult mice was shown previously to increase uterine pathology with associated alterations in the immune response and fibrosis. Reported here are uterine histopathology findings from CD1 mice exposed to BPA or 17α-ethinyl estradiol at multiple doses from conception through postnatal day 90. Along with uterine pathology, impacts of exposure on collagen accumulation and F4/80 positive macrophage numbers, as an indicator of immune response in the endometrium and myometrium, are presented. These companion data are from offspring (F1) of the dams analyzed for effects of adult exposures published in the Reproductive Toxicology manuscript titled “Strain-Specific Induction of Endometrial Periglandular Fibrosis in Mice Exposed during Adulthood to the Endocrine Disrupting Chemical Bisphenol A” (doi: 10.1016/j.reprotox.2015.08.001). DA - 2015/12// PY - 2015/12// DO - 10.1016/J.DIB.2015.10.034 VL - 5 SP - 948-953 J2 - Data in Brief LA - en OP - SN - 2352-3409 UR - http://dx.doi.org/10.1016/J.DIB.2015.10.034 DB - Crossref KW - BPA KW - Estrogen KW - EDC KW - endocrine disruption KW - Collagen KW - Fibrosis KW - Immune KW - Macrophage ER - TY - JOUR TI - Phosphorylation is an on/off switch for 5-hydroxyconiferaldehyde O-methyltransferase activity in poplar monolignol biosynthesis AU - Wang, Jack P. AU - Chuang, Ling AU - Loziuk, Philip L. AU - Chen, Hao AU - Lin, Ying-Chung AU - Shi, Rui AU - Qu, Guan-Zheng AU - Muddiman, David C. AU - Sederoff, Ronald R. AU - Chiang, Vincent L. T2 - Proceedings of the National Academy of Sciences AB - Although phosphorylation has long been known to be an important regulatory modification of proteins, no unequivocal evidence has been presented to show functional control by phosphorylation for the plant monolignol biosynthetic pathway. Here, we present the discovery of phosphorylation-mediated on/off regulation of enzyme activity for 5-hydroxyconiferaldehyde O-methyltransferase 2 (PtrAldOMT2), an enzyme central to monolignol biosynthesis for lignification in stem-differentiating xylem (SDX) of Populus trichocarpa. Phosphorylation turned off the PtrAldOMT2 activity, as demonstrated in vitro by using purified phosphorylated and unphosphorylated recombinant PtrAldOMT2. Protein extracts of P. trichocarpa SDX, which contains endogenous kinases, also phosphorylated recombinant PtrAldOMT2 and turned off the recombinant protein activity. Similarly, ATP/Mn(2+)-activated phosphorylation of SDX protein extracts reduced the endogenous SDX PtrAldOMT2 activity by ∼ 60%, and dephosphorylation fully restored the activity. Global shotgun proteomic analysis of phosphopeptide-enriched P. trichocarpa SDX protein fractions identified PtrAldOMT2 monophosphorylation at Ser(123) or Ser(125) in vivo. Phosphorylation-site mutagenesis verified the PtrAldOMT2 phosphorylation at Ser(123) or Ser(125) and confirmed the functional importance of these phosphorylation sites for O-methyltransferase activity. The PtrAldOMT2 Ser(123) phosphorylation site is conserved across 93% of AldOMTs from 46 diverse plant species, and 98% of the AldOMTs have either Ser(123) or Ser(125). PtrAldOMT2 is a homodimeric cytosolic enzyme expressed more abundantly in syringyl lignin-rich fiber cells than in guaiacyl lignin-rich vessel cells. The reversible phosphorylation of PtrAldOMT2 is likely to have an important role in regulating syringyl monolignol biosynthesis of P. trichocarpa. DA - 2015/6/24/ PY - 2015/6/24/ DO - 10.1073/PNAS.1510473112 VL - 112 IS - 27 SP - 8481-8486 J2 - Proc Natl Acad Sci USA LA - en OP - SN - 0027-8424 1091-6490 UR - http://dx.doi.org/10.1073/PNAS.1510473112 DB - Crossref KW - AldOMT KW - COMT KW - lignin KW - phosphoproteomics KW - phosphoregulation ER - TY - JOUR TI - Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds AU - Alves, Vinicius M. AU - Muratov, Eugene AU - Fourches, Denis AU - Strickland, Judy AU - Kleinstreuer, Nicole AU - Andrade, Carolina H. AU - Tropsha, Alexander T2 - Toxicology and Applied Pharmacology AB - Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71-88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. DA - 2015/4// PY - 2015/4// DO - 10.1016/J.TAAP.2014.12.014 VL - 284 IS - 2 SP - 262-272 J2 - Toxicology and Applied Pharmacology LA - en OP - SN - 0041-008X UR - http://dx.doi.org/10.1016/J.TAAP.2014.12.014 DB - Crossref KW - Skin sensitization KW - QSAR KW - Virtual screening KW - Skin toxicants ER - TY - JOUR TI - Materials Cartography: Representing and Mining Materials Space Using Structural and Electronic Fingerprints AU - Isayev, Olexandr AU - Fourches, Denis AU - Muratov, Eugene N. AU - Oses, Corey AU - Rasch, Kevin AU - Tropsha, Alexander AU - Curtarolo, Stefano T2 - Chemistry of Materials AB - As the proliferation of high-throughput approaches in materials science is increasing the wealth of data in the field, the gap between accumulated-information and derived-knowledge widens. We address the issue of scientific discovery in materials databases by introducing novel analytical approaches based on structural and electronic materials fingerprints. The framework is employed to (i) query large databases of materials using similarity concepts, (ii) map the connectivity of the materials space (i.e., as a materials cartogram) for rapidly identifying regions with unique organizations/properties, and (iii) develop predictive Quantitative Materials Structure-Property Relation- ships (QMSPR) models for guiding materials design. In this study, we test these fingerprints by seeking target material properties. As a quantitative example, we model the critical temperatures of known superconductors. Our novel materials fingerprinting and materials cartography approaches contribute to the emerging field of materials informatics by enabling effective computational tools to analyze, visualize, model, and design new materials. DA - 2015/1/17/ PY - 2015/1/17/ DO - 10.1021/CM503507H VL - 27 IS - 3 SP - 735-743 J2 - Chem. Mater. LA - en OP - SN - 0897-4756 1520-5002 UR - http://dx.doi.org/10.1021/CM503507H DB - Crossref ER - TY - JOUR TI - Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization AU - Alves, Vinicius M. AU - Muratov, Eugene AU - Fourches, Denis AU - Strickland, Judy AU - Kleinstreuer, Nicole AU - Andrade, Carolina H. AU - Tropsha, Alexander T2 - Toxicology and Applied Pharmacology AB - Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R(2)=0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q(2)ext=0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. DA - 2015/4// PY - 2015/4// DO - 10.1016/J.TAAP.2014.12.013 VL - 284 IS - 2 SP - 273-280 J2 - Toxicology and Applied Pharmacology LA - en OP - SN - 0041-008X UR - http://dx.doi.org/10.1016/J.TAAP.2014.12.013 DB - Crossref KW - Skin sensitization KW - Skin permeability KW - QSAR KW - Virtual screening KW - Skin toxicants ER - TY - JOUR TI - Drug Side Effect Profiles as Molecular Descriptors for Predictive Modeling of Target Bioactivity AU - Baker, Nancy C. AU - Fourches, Denis AU - Tropsha, Alexander T2 - Molecular Informatics AB - We have explored the potential of using side effect profiles of drugs to predict their bioactivities at the receptor level. Serotonin 5-HT6 binding and dopamine antagonism were investigated in separate studies. A set of 5-HT6 binders and non-binders was retrieved from the PDSP Ki database, whereas dopamine antagonists were retrieved from the MeSH Pharmaceutical Action file. The side effect data was extracted from ChemoText, a data repository containing MeSH annotations pulled from MEDLINE records. These side effects profiles were treated as molecular descriptors enabling a QSAR-like approach to build models that could reliably discriminate different classes of molecules, e.g., binders versus non-binders, and dopamine antagonists versus non-antagonists. Selected models with the best external prediction performances were applied to a library of ca. 1000 chemicals with known side effects profiles in order to predict their potential 5-HT6 binding and/or dopamine antagonism. In each case the virtual screening process was able to identify putatively active compounds that through subsequent literature-based validation were found to be likely or known 5-HT6 binders or dopamine antagonists. These results demonstrate that side effect profiles can be utilized to predict a drug's unknown molecular activity, thus representing a valuable opportunity in repositioning the drug for a new indications. DA - 2015/2// PY - 2015/2// DO - 10.1002/MINF.201400134 VL - 34 IS - 2-3 SP - 160-170 J2 - Mol. Inf. LA - en OP - SN - 1868-1743 UR - http://dx.doi.org/10.1002/MINF.201400134 DB - Crossref KW - Side effects KW - Machine learning KW - QSAR KW - Drug repurposing ER - TY - JOUR TI - Strain-specific induction of endometrial periglandular fibrosis in mice exposed during adulthood to the endocrine disrupting chemical bisphenol A AU - Kendziorski, Jessica A. AU - Belcher, Scott M. T2 - Reproductive Toxicology AB - The aim of this study was to compare effects of bisphenol A (BPA) on collagen accumulation in uteri of two mouse strains. Adult C57Bl/6N and CD-1 mice were exposed to dietary BPA (0.004-40mg/kg/day) or 17α-ethinyl estradiol (0.00002-0.001mg/kg/day) as effect control. An equine endometrosis-like phenotype with increased gland nesting and periglandular collagen accumulation was characteristic of unexposed C57Bl/6N, but not CD-1, endometrium. BPA non-monotonically increased gland nest density and periglandular collagen accumulation in both strains. Increased collagen I and III expression, decreased matrix metalloproteinase 2 (MMP2) and MMP14 expression, and increased immune response were associated with the endometrosis phenotype in the C57Bl/6N strain and the 30ppm BPA CD-1 group. The association between the pro-collagen shift in increased collagen expression and decreased MMP2 expression and activity implies that strain differences and BPA exposure alter regulation of endometrial remodeling and contribute to increased fibrosis, a component of several human uterine diseases. DA - 2015/12// PY - 2015/12// DO - 10.1016/J.REPROTOX.2015.08.001 VL - 58 SP - 119-130 J2 - Reproductive Toxicology LA - en OP - SN - 0890-6238 UR - http://dx.doi.org/10.1016/J.REPROTOX.2015.08.001 DB - Crossref KW - BPA KW - Endocrine disruptor KW - Uterus KW - Mouse KW - Collagen KW - Dose response KW - Endometrial periglandular fibrosis KW - Equine endometrosis KW - Matrix metalloproteinase KW - Non-monotonic ER - TY - JOUR TI - Phosphoproteome Analysis Links Protein Phosphorylation to Cellular Remodeling and Metabolic Adaptation during Magnaporthe oryzae Appressorium Development AU - Franck, William L. AU - Gokce, Emine AU - Randall, Shan M. AU - Oh, Yeonyee AU - Eyre, Alex AU - Muddiman, David C. AU - Dean, Ralph A. T2 - Journal of Proteome Research AB - The rice pathogen, Magnaporthe oryzae, undergoes a complex developmental process leading to formation of an appressorium prior to plant infection. In an effort to better understand phosphoregulation during appressorium development, a mass spectrometry based phosphoproteomics study was undertaken. A total of 2924 class I phosphosites were identified from 1514 phosphoproteins from mycelia, conidia, germlings, and appressoria of the wild type and a protein kinase A (PKA) mutant. Phosphoregulation during appressorium development was observed for 448 phosphosites on 320 phosphoproteins. In addition, a set of candidate PKA targets was identified encompassing 253 phosphosites on 227 phosphoproteins. Network analysis incorporating regulation from transcriptomic, proteomic, and phosphoproteomic data revealed new insights into the regulation of the metabolism of conidial storage reserves and phospholipids, autophagy, actin dynamics, and cell wall metabolism during appressorium formation. In particular, protein phosphorylation appears to play a central role in the regulation of autophagic recycling and actin dynamics during appressorium formation. Changes in phosphorylation were observed in multiple components of the cell wall integrity pathway providing evidence that this pathway is highly active during appressorium development. Several transcription factors were phosphoregulated during appressorium formation including the bHLH domain transcription factor MGG_05709. Functional analysis of MGG_05709 provided further evidence for the role of protein phosphorylation in regulation of glycerol metabolism and the metabolic reprogramming characteristic of appressorium formation. The data presented here represent a comprehensive investigation of the M. oryzae phosphoproteome and provide key insights on the role of protein phosphorylation during infection-related development. DA - 2015/5/15/ PY - 2015/5/15/ DO - 10.1021/PR501064Q VL - 14 IS - 6 SP - 2408-2424 J2 - J. Proteome Res. LA - en OP - SN - 1535-3893 1535-3907 UR - http://dx.doi.org/10.1021/PR501064Q DB - Crossref KW - Magnaporthe oryzae KW - quantitative phosphoproteomics KW - appressorium formation KW - network analysis KW - transcription factors ER - TY - JOUR TI - Leachate Quality Monitoring from Conventional, Retrofit, and Bio-Reactor Landfill Cells AU - Abichou, Tarek AU - Barlaz, Morton A. AU - Goldsmith, Doug AU - Green, Roger AU - Hater, Gary T2 - Journal of Hazardous, Toxic, and Radioactive Waste AB - The recirculation of leachate is a common strategy to accelerate the decomposition of municipal solid waste in landfills. In this study, leachates from a conventional landfill cell without supplemental liquid addition (Control cell), a new landfill area that had a piping network installed as waste was being placed (As-Built cell), and a conventional landfill that was modified to allow for the recirculation of liquids (Retrofit cell) were monitored at the outer loop landfill bioreactor (OLLB) in Louisville, Kentucky. In general, leachates from the Retrofit cells were statistically different from leachates from the As-Built and Control cells. This is likely because the waste in Retrofit cells was about 6 years old when liquids were first introduced and the waste had already reached a more mature state prior to supplemental liquids addition. Based on time series data, the Retrofit cells, which received nitrified leachate, did not show signs of accelerated waste decomposition based on the leachate chemistry. In contrast, there were significant differences in parameters affected by waste biodegradation [temperature, pH, biological oxygen demand (BOD), chemical oxygen demand (COD), volatile organic acid (VOA), total organic carbon (TOC)] between the As-Built and Control cells, suggesting that the introduction of liquids accelerated waste decomposition in the As-Built cells. Trends were generally similar in the As-Built cells compared to the Control cells, even though concentrations of some parameters were higher in the As-Built cells. The elevated temperature in the As-Built cells suggests more active decomposition. DA - 2015/10// PY - 2015/10// DO - 10.1061/(asce)hz.2153-5515.0000288 VL - 19 IS - 4 SP - 04015009 J2 - J. Hazard. Toxic Radioact. Waste LA - en OP - SN - 2153-5493 2153-5515 UR - http://dx.doi.org/10.1061/(asce)hz.2153-5515.0000288 DB - Crossref ER - TY - JOUR TI - A framework for incorporating ecological releases in single reservoir operation AU - Wang, Hui AU - Brill, Earl D. AU - Ranjithan, Ranji S. AU - Sankarasubramanian, A. T2 - Advances in Water Resources AB - Most reservoir operation practices consider downstream environmental flow as a constraint to meet a minimum release. The resulting flow regime may not necessarily provide downstream aquatic conditions to support healthy ecosystems. These effects can be quantified in terms of changes in values of parameters that represent the flow regimes. Numerous studies have focused on determining the ecological response to hydrological alteration caused by reservoir operation. To mitigate hydrological alteration and restore the natural flow regime as much as possible, a reservoir operation framework is proposed to explicitly incorporate ecological flow requirements. A general optimization-based decision model is presented to consider simultaneously the multiple anthropogenic uses of the reservoir and desirable ecological releases represented by parameters that capture the flow regime. Multiple uses of the reservoir, including water supply, hydropower generation, etc., are modeled as a mixed integer programming problem. Hydropower generation, which is represented by a nonlinear function that usually depends on head and water flow, is linearized using a two-dimensional function. Investigations using a reservoir in Virginia, located in the southeastern United States, demonstrate that compared to standard releases based on current operation practice, releases simulated using this framework perform better in mimicking pre-development flows. The tradeoff between anthropogenic use and ecological releases is investigated. The framework is first demonstrated for instances with perfect stream flow information. To examine the flexibility of this framework in reservoir release management, monthly flow forecasts and disaggregated daily flow conditions are incorporated. Retrospective monthly flow forecasts are obtained through regression models that use gridded precipitation forecasts and gridded soil moisture estimates as predictors. A nonparametric method is chosen to disaggregate monthly flow forecasts to daily flow conditions. Compared with daily flow climatology, forecasted monthly and daily flow better preserves flow variability and result in lower changes of flow parameters under the proposed framework. DA - 2015/4// PY - 2015/4// DO - 10.1016/j.advwatres.2015.01.006 VL - 78 SP - 9-21 J2 - Advances in Water Resources LA - en OP - SN - 0309-1708 UR - http://dx.doi.org/10.1016/j.advwatres.2015.01.006 DB - Crossref KW - Ecological flow requirements KW - Natural flow regime KW - Sustainable reservoir operation KW - Mixed integer linear programming ER - TY - JOUR TI - Role of multimodel combination and data assimilation in improving streamflow prediction over multiple time scales AU - Li, Weihua AU - Sankarasubramanian, A. AU - Ranjithan, R. S. AU - Sinha, Tushar T2 - Stochastic Environmental Research and Risk Assessment DA - 2015/9/24/ PY - 2015/9/24/ DO - 10.1007/s00477-015-1158-6 VL - 30 IS - 8 SP - 2255-2269 J2 - Stoch Environ Res Risk Assess LA - en OP - SN - 1436-3240 1436-3259 UR - http://dx.doi.org/10.1007/s00477-015-1158-6 DB - Crossref ER - TY - JOUR TI - Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma AU - Igartua, Catherine AU - Myers, Rachel A. AU - Mathias, Rasika A. AU - Pino-Yanes, Maria AU - Eng, Celeste AU - Graves, Penelope E. AU - Levin, Albert M. AU - Del-Rio-Navarro, Blanca E. AU - Jackson, Daniel J. AU - Livne, Oren E. AU - Rafaels, Nicholas AU - Edlund, Christopher K. AU - Yang, James J. AU - Huntsman, Scott AU - Salam, Muhammad T. AU - Romieu, Isabelle AU - Mourad, Raphael AU - Gern, James E. AU - Lemanske, Robert F. AU - Wyss, Annah AU - Hoppin, Jane A. AU - Barnes, Kathleen C. AU - Burchard, Esteban G. AU - Gauderman, W. James AU - Martinez, Fernando D. AU - Raby, Benjamin A. AU - Weiss, Scott T. AU - Williams, L. Keoki AU - London, Stephanie J. AU - Gilliland, Frank D. AU - Nicolae, Dan L. AU - Ober, Carole T2 - Nature Communications AB - Abstract Common variants at many loci have been robustly associated with asthma but explain little of the overall genetic risk. Here we investigate the role of rare (<1%) and low-frequency (1–5%) variants using the Illumina HumanExome BeadChip array in 4,794 asthma cases, 4,707 non-asthmatic controls and 590 case–parent trios representing European Americans, African Americans/African Caribbeans and Latinos. Our study reveals one low-frequency missense mutation in the GRASP gene that is associated with asthma in the Latino sample ( P =4.31 × 10 −6 ; OR=1.25; MAF=1.21%) and two genes harbouring functional variants that are associated with asthma in a gene-based analysis: GSDMB at the 17q12–21 asthma locus in the Latino and combined samples ( P =7.81 × 10 −8 and 4.09 × 10 −8 , respectively) and MTHFR in the African ancestry sample ( P =1.72 × 10 −6 ). Our results suggest that associations with rare and low-frequency variants are ethnic specific and not likely to explain a significant proportion of the ‘missing heritability’ of asthma. DA - 2015/1/16/ PY - 2015/1/16/ DO - 10.1038/ncomms6965 VL - 6 IS - 1 J2 - Nat Commun LA - en OP - SN - 2041-1723 UR - http://dx.doi.org/10.1038/ncomms6965 DB - Crossref ER - TY - JOUR TI - Associations of Ozone and PM2.5 Concentrations With Parkinsonʼs Disease Among Participants in the Agricultural Health Study AU - Kirrane, Ellen F. AU - Bowman, Christal AU - Davis, J. Allen AU - Hoppin, Jane A. AU - Blair, Aaron AU - Chen, Honglei AU - Patel, Molini M. AU - Sandler, Dale P. AU - Tanner, Caroline M. AU - Vinikoor-Imler, Lisa AU - Ward, Mary H. AU - Luben, Thomas J. AU - Kamel, Freya T2 - Journal of Occupational and Environmental Medicine AB - Objective: This study describes associations of ozone and fine particulate matter with Parkinson's disease observed among farmers in North Carolina and Iowa. Methods: We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants' geocoded addresses. Results: We observed positive associations of Parkinson's disease with ozone (odds ratio = 1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95% CI: 0.93 to 1.93) in North Carolina but not in Iowa. Conclusions: The plausibility of an effect of ambient concentrations of these pollutants on Parkinson's disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed. DA - 2015/5// PY - 2015/5// DO - 10.1097/JOM.0000000000000451 VL - 57 IS - 5 SP - 509-517 J2 - Journal of Occupational and Environmental Medicine LA - en OP - SN - 1076-2752 UR - http://dx.doi.org/10.1097/JOM.0000000000000451 DB - Crossref ER - TY - JOUR TI - IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans AU - Pearce, Neil AU - Blair, Aaron AU - Vineis, Paolo AU - Ahrens, Wolfgang AU - Andersen, Aage AU - Anto, Josep M. AU - Armstrong, Bruce K. AU - Baccarelli, Andrea A. AU - Beland, Frederick A. AU - Berrington, Amy AU - Bertazzi, Pier Alberto AU - Birnbaum, Linda S. AU - Brownson, Ross C. AU - Bucher, John R. AU - Cantor, Kenneth P. AU - Cardis, Elisabeth AU - Cherrie, John W. AU - Christiani, David C. AU - Cocco, Pierluigi AU - Coggon, David AU - Comba, Pietro AU - Demers, Paul A. AU - Dement, John M. AU - Douwes, Jeroen AU - Eisen, Ellen A. AU - Engel, Lawrence S. AU - Fenske, Richard A. AU - Fleming, Lora E. AU - Fletcher, Tony AU - Fontham, Elizabeth AU - Forastiere, Francesco AU - Frentzel-Beyme, Rainer AU - Fritschi, Lin AU - Gerin, Michel AU - Goldberg, Marcel AU - Grandjean, Philippe AU - Grimsrud, Tom K. AU - Gustavsson, Per AU - Haines, Andy AU - Hartge, Patricia AU - Hansen, Johnni AU - Hauptmann, Michael AU - Heederik, Dick AU - Hemminki, Kari AU - Hemon, Denis AU - Hertz-Picciotto, Irva AU - Hoppin, Jane A. AU - Huff, James AU - Jarvholm, Bengt AU - Kang, Daehee AU - Karagas, Margaret R. AU - Kjaerheim, Kristina AU - Kjuus, Helge AU - Kogevinas, Manolis AU - Kriebel, David AU - Kristensen, Petter AU - Kromhout, Hans AU - Laden, Francine AU - Lebailly, Pierre AU - LeMasters, Grace AU - Lubin, Jay H. AU - Lynch, Charles F. AU - Lynge, Elsebeth AU - ‘t Mannetje, Andrea AU - McMichael, Anthony J. AU - McLaughlin, John R. AU - Marrett, Loraine AU - Martuzzi, Marco AU - Merchant, James A. AU - Merler, Enzo AU - Merletti, Franco AU - Miller, Anthony AU - Mirer, Franklin E. AU - Monson, Richard AU - Nordby, Karl-Cristian AU - Olshan, Andrew F. AU - Parent, Marie-Elise AU - Perera, Frederica P. AU - Perry, Melissa J. AU - Pesatori, Angela Cecilia AU - Pirastu, Roberta AU - Porta, Miquel AU - Pukkala, Eero AU - Rice, Carol AU - Richardson, David B. AU - Ritter, Leonard AU - Ritz, Beate AU - Ronckers, Cecile M. AU - Rushton, Lesley AU - Rusiecki, Jennifer A. AU - Rusyn, Ivan AU - Samet, Jonathan M. AU - Sandler, Dale P. AU - de Sanjose, Silvia AU - Schernhammer, Eva AU - Costantini, Adele Seniori AU - Seixas, Noah AU - Shy, Carl AU - Siemiatycki, Jack AU - Silverman, Debra T. AU - Simonato, Lorenzo AU - Smith, Allan H. AU - Smith, Martyn T. AU - Spinelli, John J. AU - Spitz, Margaret R. AU - Stallones, Lorann AU - Stayner, Leslie T. AU - Steenland, Kyle AU - Stenzel, Mark AU - Stewart, Bernard W. AU - Stewart, Patricia A. AU - Symanski, Elaine AU - Terracini, Benedetto AU - Tolbert, Paige E. AU - Vainio, Harri AU - Vena, John AU - Vermeulen, Roel AU - Victora, Cesar G. AU - Ward, Elizabeth M. AU - Weinberg, Clarice R. AU - Weisenburger, Dennis AU - Wesseling, Catharina AU - Weiderpass, Elisabete AU - Zahm, Shelia Hoar T2 - Environmental Health Perspectives AB - Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed.We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health. DA - 2015/6// PY - 2015/6// DO - 10.1289/ehp.1409149 VL - 123 IS - 6 SP - 507-514 J2 - Environmental Health Perspectives LA - en OP - SN - 0091-6765 1552-9924 UR - http://dx.doi.org/10.1289/ehp.1409149 DB - Crossref ER - TY - JOUR TI - Enhancing bottom-up and top-down proteomic measurements with ion mobility separations AU - Baker, E.S. AU - Burnum-Johnson, K.E. AU - Ibrahim, Y.M. AU - Orton, D.J. AU - Monroe, M.E. AU - Kelly, R.T. AU - Moore, R.J. AU - Zhang, X. AU - Théberge, R. AU - Costello, C.E. AU - Smith, R.D. T2 - Proteomics AB - Proteomic measurements with greater throughput, sensitivity, and structural information are essential for improving both in-depth characterization of complex mixtures and targeted studies. While LC separation coupled with MS (LC-MS) measurements have provided information on thousands of proteins in different sample types, the introduction of a separation stage that provides further component resolution and rapid structural information has many benefits in proteomic analyses. Technical advances in ion transmission and data acquisition have made ion mobility separations an opportune technology to be easily and effectively incorporated into LC-MS proteomic measurements for enhancing their information content. Herein, we report on applications illustrating increased sensitivity, throughput, and structural information by utilizing IMS-MS and LC-IMS-MS measurements for both bottom-up and top-down proteomics measurements. DA - 2015/// PY - 2015/// DO - 10.1002/pmic.201500048 VL - 15 IS - 16 SP - 2766-2776 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84938738882&partnerID=MN8TOARS KW - Ion mobility separations KW - Ion mobility spectrometry KW - Mass spectrometry KW - Proteomics ER - TY - JOUR TI - Enhancing biological analyses with three dimensional field asymmetric ion mobility, low field drift tube ion mobility and mass spectrometry (μFAIMS/IMS-MS) separations AU - Zhang, X. AU - Ibrahim, Y.M. AU - Chen, T.-C. AU - Kyle, J.E. AU - Norheim, R.V. AU - Monroe, M.E. AU - Smith, R.D. AU - Baker, E.S. T2 - Analyst AB - Novel μFAIMS/IMS-MS three dimensional separations were optimized to enhance separation power and selectivity in biological analyses. DA - 2015/// PY - 2015/// DO - 10.1039/c5an00897b VL - 140 IS - 20 SP - 6955-6963 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84942612537&partnerID=MN8TOARS ER - TY - JOUR TI - Development of a new ion mobility (quadrupole) time-of-flight mass spectrometer AU - Ibrahim, Y.M. AU - Baker, E.S. AU - Danielson, W.F. AU - Norheim, R.V. AU - Prior, D.C. AU - Anderson, G.A. AU - Belov, M.E. AU - Smith, R.D. T2 - International Journal of Mass Spectrometry AB - A new ion mobility spectrometer (IMS) platform was developed to improve upon the sensitivity and reproducibility of our previous platforms, and further enhance IMS-MS utility for broad 'pan-omics' measurements. The new platform incorporated an improved electrospray ionization source and interface for enhanced sensitivity, and providing the basis for further benefits based upon implementation of multiplexed IMS. The ion optics included electrodynamic ion funnels at both the entrance and exit of the IMS, an ion funnel trap for ion injection, and a design in which nearly all ion optics (e.g. drift rings, ion funnels) were fabricated using printed circuit board technology. The IMS resolving power achieved was ~73 for singly-charged ions, very close to the predicted diffusion-limited resolving power (~75). The platform's performance evaluation (e.g. for proteomics measurements) include LC-IMS-TOF MS datasets for 30 technical replicates for a trypsin digested human serum, and included platform performance in each dimension (LC, IMS and MS) separately. DA - 2015/// PY - 2015/// DO - 10.1016/j.ijms.2014.07.034 VL - 377 IS - 1 SP - 655-662 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85027921067&partnerID=MN8TOARS ER - TY - JOUR TI - Muscle Segment Homeobox Genes Direct Embryonic Diapause by Limiting Inflammation in the Uterus AU - Cha, Jeeyeon AU - Burnum-Johnson, Kristin E. AU - Bartos, Amanda AU - Li, Yingju AU - Baker, Erin S. AU - Tilton, Susan C. AU - Webb-Robertson, Bobbie-Jo M. AU - Piehowski, Paul D. AU - Monroe, Matthew E. AU - Jegga, Anil G. AU - Murata, Shigeo AU - Hirota, Yasushi AU - Dey, Sudhansu K. T2 - Journal of Biological Chemistry AB - Embryonic diapause is a reproductive strategy widespread in the animal kingdom. This phenomenon is defined by a temporary arrest in blastocyst growth and metabolic activity within a quiescent uterus without implantation until the environmental and maternal milieu become favorable for pregnancy to progress. We found that uterine Msx expression persists during diapause across species; their inactivation in the mouse uterus results in termination of diapause with the development of implantation-like responses (“pseudoimplantation”) that ultimately succumbed to resorption. To understand the cause of this failure, we compared proteome profiles between floxed and Msx-deleted uteri. In deleted uteri, several functional networks, including transcription/translation, ubiquitin-proteasome, inflammation, and endoplasmic reticulum stress, were dysregulated. Computational modeling predicted intersection of these pathways on an enhanced inflammatory signature. Further studies showed that this signature was reflected in increased phosphorylated IκB levels and nuclear NFκB in deleted uteri. This was associated with enhanced proteasome activity and endoplasmic reticulum stress. Interestingly, treatment with anti-inflammatory glucocorticoid (dexamethasone) reduced the inflammatory signature with improvement of the diapause phenotype. These findings highlight an unexpected role of uterine Msx in limiting aberrant inflammatory responses to maintain embryonic diapause. Embryonic diapause is a reproductive strategy widespread in the animal kingdom. This phenomenon is defined by a temporary arrest in blastocyst growth and metabolic activity within a quiescent uterus without implantation until the environmental and maternal milieu become favorable for pregnancy to progress. We found that uterine Msx expression persists during diapause across species; their inactivation in the mouse uterus results in termination of diapause with the development of implantation-like responses (“pseudoimplantation”) that ultimately succumbed to resorption. To understand the cause of this failure, we compared proteome profiles between floxed and Msx-deleted uteri. In deleted uteri, several functional networks, including transcription/translation, ubiquitin-proteasome, inflammation, and endoplasmic reticulum stress, were dysregulated. Computational modeling predicted intersection of these pathways on an enhanced inflammatory signature. Further studies showed that this signature was reflected in increased phosphorylated IκB levels and nuclear NFκB in deleted uteri. This was associated with enhanced proteasome activity and endoplasmic reticulum stress. Interestingly, treatment with anti-inflammatory glucocorticoid (dexamethasone) reduced the inflammatory signature with improvement of the diapause phenotype. These findings highlight an unexpected role of uterine Msx in limiting aberrant inflammatory responses to maintain embryonic diapause. DA - 2015/// PY - 2015/// DO - 10.1074/jbc.M115.655001 VL - 290 IS - 24 SP - 15337-15349 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000356177300044&KeyUID=WOS:000356177300044 ER - TY - BOOK TI - Mass spectrometry for biomarker development AU - Wu, C. AU - Liu, T. AU - Baker, E.S. AU - Rodland, K.D. AU - Smith, R.D. AB - Biomarkers potentially play a crucial role in early disease diagnosis, prognosis, and targeted therapy. In the past decade, mass spectrometry-based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g., shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy across the different stages of biomarker development, with a particular emphasis on blood-based biomarker development. DA - 2015/// PY - 2015/// DO - 10.1007/978-94-007-7696-8_21 VL - 1-2 SE - 17-48 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84958696691&partnerID=MN8TOARS ER - TY - JOUR TI - Ion manipulations in structures for lossless ion manipulations (SLIM): computational evaluation of a 90° turn and a switch. AU - Garimella, Sandilya V B AU - Ibrahim, Yehia M AU - Webb, Ian K AU - Ipsen, Andreas B AU - Chen, Tsung-Chi AU - Tolmachev, Aleksey V AU - Baker, Erin S AU - Anderson, Gordon A AU - Smith, Richard D T2 - The Analyst AB - The process of redirecting ions through 90° turns and 'tee' switches utilizing Structures for Lossless Ion Manipulations (SLIM) was evaluated at 4 Torr pressure using SIMION simulations and theoretical methods. The nature of pseudo-potential in SLIM-tee structures has also been explored. Simulations show that 100% transmission efficiency in SLIM devices can be achieved with guard electrode voltages lower than ∼10 V. The ion plume width in these conditions is ∼1.6 mm while at lower guard voltages lead to greater plume widths. Theoretical calculations show marginal loss of ion mobility resolving power (<5%) during ion turn due to the finite plume widths (i.e. race track effect). More robust SLIM designs that reduce the race track effect while maximizing ion transmission are also reported. In addition to static turns, the dynamic switching of ions into orthogonal channels was also evaluated both using SIMION ion trajectory simulations and experimentally. Simulations and theoretical calculations were in close agreement with experimental results and were used to develop more refined SLIM designs. DA - 2015/// PY - 2015/// DO - 10.1039/c5an00844a VL - 140 IS - 20 SP - 6845-52 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=MEDLINE&KeyUT=MEDLINE:26289106&KeyUID=MEDLINE:26289106 ER - TY - JOUR TI - Ion Trapping, Storage, and Ejection in Structures for Lossless Ion Manipulations AU - Zhang, X. AU - Garimella, S.V.B. AU - Prost, S.A. AU - Webb, I.K. AU - Chen, T.-C. AU - Tang, K. AU - Tolmachev, A.V. AU - Norheim, R.V. AU - Baker, E.S. AU - Anderson, G.A. AU - Ibrahim, Y.M. AU - Smith, R.D. T2 - Analytical Chemistry AB - A new Structures for Lossless Ion Manipulations (SLIM) module, having electrode arrays patterned on a pair of parallel printed circuit boards (PCB), was constructed and utilized to investigate capabilities for ion trapping at a pressure of 4 Torr. Positive ions were confined by application of RF voltages to a series of inner rung electrodes with alternating phase on adjacent electrodes, in conjunction with positive DC potentials on surrounding guard electrodes on each PCB. An axial DC field was also introduced by stepwise varying the DC potentials applied to the inner rung electrodes to control the ion transport and accumulation inside the ion trapping region. We show that ions can be trapped and accumulated with up to 100% efficiency, stored for at least 5 h with no significant losses, and then could be rapidly ejected from the SLIM trap. The present results provide a foundation for the development of much more complex SLIM devices that facilitate extended ion manipulations. DA - 2015/// PY - 2015/// DO - 10.1021/acs.analchem.5b00214 VL - 87 IS - 12 SP - 6010-6016 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000356755100023&KeyUID=WOS:000356755100023 ER - TY - JOUR TI - Pesticide use and risk of end-stage renal disease among licensed pesticide applicators in the Agricultural Health Study AU - Lebov, Jill F AU - Engel, Lawrence S AU - Richardson, David AU - Hogan, Susan L AU - Hoppin, Jane A AU - Sandler, Dale P T2 - Occupational and Environmental Medicine AB - Experimental studies suggest a relationship between pesticide exposure and renal impairment, but epidemiological evidence is limited. We evaluated the association between exposure to 39 specific pesticides and end-stage renal disease (ESRD) incidence in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina.Via linkage to the US Renal Data System, we identified 320 ESRD cases diagnosed between enrolment (1993-1997) and December 2011 among 55 580 male licensed pesticide applicators. Participants provided information on use of pesticides via self-administered questionnaires. Lifetime pesticide use was defined as the product of duration and frequency of use and then modified by an intensity factor to account for differences in pesticide application practices. Cox proportional hazards models, adjusted for age and state, were used to estimate associations between ESRD and: (1) ordinal categories of intensity-weighted lifetime use of 39 pesticides, (2) poisoning and high-level pesticide exposures and (3) pesticide exposure resulting in a medical visit or hospitalisation.Positive exposure-response trends were observed for the herbicides alachlor, atrazine, metolachlor, paraquat, and pendimethalin, and the insecticide permethrin. More than one medical visit due to pesticide use (HR=2.13; 95% CI 1.17 to 3.89) and hospitalisation due to pesticide use (HR=3.05; 95% CI 1.67 to 5.58) were significantly associated with ESRD.Our findings support an association between ESRD and chronic exposure to specific pesticides, and suggest pesticide exposures resulting in medical visits may increase the risk of ESRD.Clinicaltrials.gov NCT00352924. DA - 2015/7/15/ PY - 2015/7/15/ DO - 10.1136/oemed-2014-102615 VL - 73 IS - 1 SP - 3-12 J2 - Occup Environ Med LA - en OP - SN - 1351-0711 1470-7926 UR - http://dx.doi.org/10.1136/oemed-2014-102615 DB - Crossref ER - TY - CONF TI - Integrating literature-based curated data to predict mechanisms of toxicity AU - Mattingly, C.J. T2 - OpenTox USA 2015 C2 - 2015/// CY - Baltimore, MD DA - 2015/// PY - 2015/2/10/ ER - TY - JOUR TI - Impact of low-dose oral exposure to bisphenol A (BPA) on Juvenile and adult rat exploratory and anxiety behavior: A CLARITY-BPA Consortium Study AU - Rebuli, M.E. AU - Camacho, L. AU - Adonay, M.E. AU - Reif, D.M. AU - Aylor, D.L. AU - Patisaul, H.B. T2 - Toxicological Sciences AB - Bisphenol A (BPA) is a high volume production chemical and has been identified as an endocrine disruptor, prompting concern that developmental exposure could impact brain development and behavior. Rodent and human studies suggest that early life BPA exposure may result in an anxious, hyperactive phenotype but results are conflicting and data from studies using multiple doses below the no-observed-adverse-effect level are limited. To address this, the present studies were conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program. The impact of perinatal BPA exposure (2.5, 25, or 2500 µg/kg body weight (bw)/day) on behaviors related to anxiety and exploratory activity was assessed in juvenile (prepubertal) and adult NCTR Sprague-Dawley rats of both sexes. Ethinyl estradiol (0.5 µg/kg bw/day) was used as a reference estrogen. Exposure spanned gestation and lactation with dams gavaged from gestational day 6 until birth and then the offspring gavaged directly through weaning (n = 12/sex/group). Behavioral assessments included open field, elevated plus maze, and zero maze. Anticipated sex differences in behavior were statistically identified or suggested in most cases. No consistent effects of BPA were observed for any endpoint, in either sex, at either age compared to vehicle controls; however, significant differences between BPA-exposed and ethinyl estradiol-exposed groups were identified for some endpoints. Limitations of this study are discussed and include suboptimal statistical power and low concordance across behavioral tasks. These data do not indicate BPA-related effects on anxiety or exploratory activity in these developmentally exposed rats. DA - 2015/// PY - 2015/// DO - 10.1093/toxsci/kfv163 VL - 148 IS - 2 SP - 341-354 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84952932385&partnerID=MN8TOARS KW - bisphenol A KW - CLARITY KW - behavior KW - anxiety KW - exploratory activity KW - endocrine disruption KW - EDC KW - sexually dimorphic KW - brain KW - BPA KW - plastic ER - TY - JOUR TI - Food for Thought...: Toxicity testing in the 21st century beyond environmental chemicals AU - Rovida, C. AU - Asakura, S. AU - Daneshian, M. AU - Hofman-Huether, H. AU - Leist, M. AU - Meunier, L. AU - Reif, D. AU - Rossi, A. AU - Schmutz, M. AU - Valentin, J.-P. AU - Zurlo, J. AU - Hartung, T. T2 - Altex AB - After the publication of the report titled Toxicity Testing in the 21st Century – A Vision and a Strategy, many initiatives started to foster a major paradigm shift for toxicity testing – from apical endpoints in animal-based tests to mechanistic endpoints through delineation of pathways of toxicity (PoT) in human cell based systems. The US EPA has funded an important project to develop new high throughput technologies based on human cell based in vitro technologies. These methods are currently being incorporated into the chemical risk assessment process. In the pharmaceutical industry, the efficacy and toxicity of new drugs are evaluated during preclinical investigations that include drug metabolism, pharmacokinetics, pharmacodynamics and safety toxicology studies. The results of these studies are analyzed and extrapolated to predict efficacy and potential adverse effects in humans. However, due to the high failure rate of drugs during the clinical phases, a new approach for a more predictive assessment of drugs both in terms of efficacy and adverse effects is getting urgent. The food industry faces the challenge of assessing novel foods and food ingredients for the general population, while using animal safety testing for extrapolation purposes is often of limited relevance. The question is whether the latest paradigm shift proposed by the Tox21c report for chemicals may provide a useful tool to improve the risk assessment approach also for drugs and food ingredients. DA - 2015/// PY - 2015/// DO - 10.14573/altex.1506201 VL - 32 IS - 3 SP - 171-181 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84938603406&partnerID=MN8TOARS KW - food ingredients KW - drugs KW - Tox21c KW - safety assessment ER - TY - BOOK TI - Embracing complexity: Searching for gene-gene and gene environment interactions in genetic epidemiology AU - Motsinger, A.A. AU - Reif, D.M. DA - 2015/// PY - 2015/// DO - 10.1201/b18597 SE - 19-58 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85053966420&partnerID=MN8TOARS ER - TY - JOUR TI - Data-driven asthma endotypes defined from blood biomarker and gene expression data AU - George, B.J. AU - Reif, D.M. AU - Gallagher, J.E. AU - Williams-DeVane, C.R. AU - Heidenfelder, B.L. AU - Hudgens, E.E. AU - Jones, W. AU - Neas, L. AU - Cohen Hubal, E.A. AU - Edwards, S.W. T2 - PLoS ONE AB - The diagnosis and treatment of childhood asthma is complicated by its mechanistically distinct subtypes (endotypes) driven by genetic susceptibility and modulating environmental factors. Clinical biomarkers and blood gene expression were collected from a stratified, cross-sectional study of asthmatic and non-asthmatic children from Detroit, MI. This study describes four distinct asthma endotypes identified via a purely data-driven method. Our method was specifically designed to integrate blood gene expression and clinical biomarkers in a way that provides new mechanistic insights regarding the different asthma endotypes. For example, we describe metabolic syndrome-induced systemic inflammation as an associated factor in three of the four asthma endotypes. Context provided by the clinical biomarker data was essential in interpreting gene expression patterns and identifying putative endotypes, which emphasizes the importance of integrated approaches when studying complex disease etiologies. These synthesized patterns of gene expression and clinical markers from our research may lead to development of novel serum-based biomarker panels. DA - 2015/// PY - 2015/// DO - 10.1371/journal.pone.0117445 VL - 10 IS - 2 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84922569392&partnerID=MN8TOARS ER - TY - BOOK TI - Computational Methods Used in Systems Biology AU - Meisner, M. AU - Reif, D.M. AB - The overarching theme of systems biology is that of complex interactions between multiscale systems, so it follows that computational methods used in systems biology aim to integrate data and originate from an interdisciplinary slate of scientific fields. To deal with “omic” data generation discussed in previous chapters, suitable analysis methods for systems biology must account for measurements made across scales of time, space, and biological organization. Importantly, analysis methods must first account for the specifics (and peculiarities) of individual technology platforms. For the more established platforms, such as chip hybridization and sequencing techniques, progress in computational methods research has resulted in a trend toward standardization, where coalescence of statistical methods into powerful software packages handle early stages of analysis in a generally accepted manner. For emerging platforms, computational methods remain diffuse, although popular approaches share many statistical similarities with more mature methods. Once individual data components have been analyzed, integration into a systems framework can begin. DA - 2015/// PY - 2015/// DO - 10.1016/B978-0-12-801564-3.00005-5 SE - 85-115 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84940026164&partnerID=MN8TOARS ER - TY - JOUR TI - Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing AU - Ducharme, N.A. AU - Reif, D.M. AU - Gustafsson, J.-A. AU - Bondesson, M. T2 - Reproductive Toxicology AB - With the high cost and slow pace of toxicity testing in mammals, the vertebrate zebrafish has become a tractable model organism for high throughput toxicity testing. We present here a meta-analysis of 600 chemicals tested for toxicity in zebrafish embryos and larvae. Nineteen aggregated and 57 individual toxicity endpoints were recorded from published studies yielding 2695 unique data points. These data points were compared to lethality and reproductive toxicology endpoints analyzed in rodents and rabbits and to exposure values for humans. We show that although many zebrafish endpoints did not correlate to rodent or rabbit acute toxicity data, zebrafish could be used to accurately predict relative acute toxicity through the rat inhalation, rabbit dermal, and rat oral exposure routes. Ranking of the chemicals based on toxicity and teratogenicity in zebrafish, as well as human exposure levels, revealed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene, and chlorpyrifos ranked in the top nine of all chemicals for these three categories, and as such should be considered high priority chemicals for testing in higher vertebrates. DA - 2015/// PY - 2015/// DO - 10.1016/j.reprotox.2014.09.005 VL - 55 SP - 3-10 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84939415843&partnerID=MN8TOARS KW - Meta-analysis KW - Toxicity KW - Teratogen KW - Zebrafish KW - Human exposure ER - TY - JOUR TI - Carcinogenicity of lindane, DDT, and 2,4-dichlorophenoxyacetic acid. AU - Loomis, D AU - Guyton, K AU - Grosse, Y AU - El, Ghissasi F AU - Bouvard, V AU - Benbrahim-Tallaa, L AU - Guha, N AU - Mattock, H AU - Straif, K AU - France T2 - The Lancet. Oncology AB - Lancet Oncology, The - In Press.Proof corrected by the author Available online since mercredi 24 juin 2015 DA - 2015/8// PY - 2015/8// DO - 10.1016/s1470-2045(15)00081-9 VL - 8 UR - http://europepmc.org/abstract/med/26111929 ER - TY - JOUR TI - Part 2: Sensitivity comparisons of the mayfly Centroptilum triangulifer to Ceriodaphnia dubia and Daphnia magna using standard reference toxicants; NaCl, KCl and CuSO4 AU - Struewing, Katherine A. AU - Lazorchak, James M. AU - Weaver, Paul C. AU - Johnson, Brent R. AU - Funk, David H. AU - Buchwalter, David B. T2 - CHEMOSPHERE AB - Criteria for establishing water quality standards that are protective for 95% of the native species are generally based upon laboratory toxicity tests. These tests utilize common model organisms that have established test methods. However, for invertebrates these species represent mostly the zooplankton community and are not inclusive of all taxa. In order to examine a potential under-representation in emerging aquatic invertebrates the US Environmental Protection Agency has cultured a parthenogenetic mayfly, Centroptilum triangulifer (Ephemeroptera: Baetidae). This study established a 48 h acute and a 14-day short-term chronic testing procedure for C. triangulifer and compared its sensitivity to two model invertebrates, Ceriodaphnia dubia and Daphnia magna. Toxicity tests were conducted to determine mortality and growth effects using standard reference toxicants: NaCl, KCl and CuSO4. In 48-h acute tests, the average LC50 for the mayfly was 659 mg L−1 NaCl, 1957 mg L−1 KCl, and 11 μg L−1 CuSO4. IC25 values, using dry weight as the endpoint, were 228 mg L−1 NaCl, 356 mg L−1 KCl and 5 μg L−1 CuSO4. C. triangulifer was the most sensitive species in NaCl acute and chronic growth tests. At KCl concentrations tested, C. triangulifer was less sensitive for acute tests but was equally or more sensitive than C. dubia and D. magna for growth measurements. This study determined C. triangulifer has great potential and benefits for use in ecotoxicological studies. DA - 2015/11// PY - 2015/11// DO - 10.1016/j.chemosphere.2014.04.096 VL - 139 SP - 597-603 SN - 1879-1298 KW - Mayfly KW - Comparative toxicity KW - NaCl KW - KCl KW - CuSO4 ER - TY - JOUR TI - Part 1: Laboratory culture of Centroptilum triangulifer (Ephemeroptera: Baetidae) using a defined diet of three diatoms AU - Weaver, Paul C. AU - Lazorchak, James M. AU - Struewing, Katherine A. AU - DeCelles, Susanna J. AU - Funk, David H. AU - Buchwalter, David B. AU - Johnson, Brent R. T2 - CHEMOSPHERE AB - Development of methods for assessing exposure and effects of waterborne toxicants on stream invertebrate species is important to elucidate environmentally relevant information. Current protocols for freshwater invertebrate toxicity testing almost exclusively utilize cladocerans, amphipods or chironomids rather than the more typical aquatic insect taxa found in lotic systems. Centroptilum triangulifer is a parthenogenetic mayfly occurring in depositional habitats of streams and rivers of the Eastern U.S. and Canada. C. triangulifer is an ideal stream insect for toxicity testing under field and laboratory conditions because of its short life cycle, parthenogenetic mode of reproduction, and it represents a group considered sensitive to environmental stressors. In this study, a colony of C. triangulifer was reared using a defined diet of three diatoms, Mayamaea atomus var. permitis, Nitzschia cf. pusilla, and Achnanthidium minutissimum. Percent survival (⩾80%), fecundity measurements (⩾1000 eggs) and pre-egg laying weights were used as indicators of overall colony health and fitness in our laboratory water (Lab-line) and in Moderately Hard Reconstituted Water (MHRW). Lab-line reared C. triangulifer had average survival rate of 92.69% for eleven generations and 82.99% over thirteen generations. MHRW reared C. triangulifer had an average survival rate of 80.65% for four generations and three generations of fecundities greater than 1000 eggs per individual. Pre-egg laying weight and fecundity were highly correlated and a best-fit model equation was derived to estimate egg counts for future generations. Establishment of this culturing protocol provides a more ecologically relevant species for toxicity testing and aids in further stressor identification for stream bioassessments. DA - 2015/11// PY - 2015/11// DO - 10.1016/j.chemosphere.2014.04.092 VL - 139 SP - 589-596 SN - 1879-1298 KW - Benthic macroinvertebrates KW - Water quality criteria KW - Ecotoxicology KW - Parthenogenetic mayfly KW - Culture method KW - Diatoms ER - TY - JOUR TI - Opinions of clinical veterinarians at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections AU - Jacob, Megan E. AU - Hoppin, Jane A. AU - Steers, Nicola AU - Davis, Jennifer L. AU - Davidson, Gigi AU - Hansen, Bernie AU - Lunn, Katharine F. AU - Murphy, K. Marcia AU - Papich, Mark G. T2 - Journal of the American Veterinary Medical Association AB - Abstract Objective —To determine opinions of faculty members with clinical appointments, clinical veterinarians, residents, and interns at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections. Design —Cross-sectional survey. Sample —71 veterinarians. Procedures —An online questionnaire was sent to all veterinarians with clinical service responsibilities at the North Carolina State University veterinary teaching hospital (n = 167). The survey included 23 questions regarding demographic information, educational experiences, current prescribing practices, and personal opinions related to antimicrobial selection, antimicrobial use, restrictions on antimicrobial use, and antimicrobial resistance. Results —Of the 167 veterinarians eligible to participate, 71 (43%) responded. When respondents were asked to rate their level of concern (very concerned = 1; not concerned = 5) about antimicrobial-resistant infections, most (41/70 [59%]) assigned a score of 1, with mean score for all respondents being 1.5. Most survey participants rated their immediate colleagues (mean score, 1.9) as more concerned than other veterinary medical professionals (mean score, 2.3) and their clients (mean score, 3.4). Fifty-nine of 67 (88%) respondents felt that antimicrobials were overprescribed at the hospital, and 32 of 69 (46%) respondents felt uncomfortable prescribing at least one class of antimicrobials (eg, carbapenems or glycopeptides) because of public health concerns. Conclusions and Clinical Relevance —Findings indicated that veterinarians at this teaching hospital were concerned about antimicrobial resistance, thought antimicrobials were overprescribed, and supported restricting use of certain antimicrobial classes in companion animals. Findings may be useful in educating future veterinarians and altering prescribing habits and antimicrobial distribution systems in veterinary hospitals. DA - 2015/10/15/ PY - 2015/10/15/ DO - 10.2460/javma.247.8.938 VL - 247 IS - 8 SP - 938-944 J2 - Journal of the American Veterinary Medical Association LA - en OP - SN - 0003-1488 UR - http://dx.doi.org/10.2460/javma.247.8.938 DB - Crossref ER - TY - JOUR TI - Meeting multiple water quality objectives through treatment using locally generated char: improving organoleptic properties and removing synthetic organic contaminants and disinfection by-products AU - Kearns, Joshua P. AU - Shimabuku, Kyle K. AU - Mahoney, Ryan B. AU - Knappe, Detlef R. U. AU - Summers, R. Scott T2 - JOURNAL OF WATER SANITATION AND HYGIENE FOR DEVELOPMENT AB - A variety of natural and anthropogenic contaminants can compromise the safety and esthetics of surface water collected for drinking and disinfected using chlorine by households in developing communities. While household chlorination is effective against most microbial pathogens, many users find the taste and odor of chlorine unacceptable and revert to drinking untreated water. Moreover, reactions between chlorine and the dissolved organic matter form harmful disinfection by-products (DBPs) such as trihalomethanes (THMs). Char adsorbers have been used to treat drinking water for thousands of years and are still widely used today. Results obtained here demonstrate that locally produced biomass chars (biochars) exhibit removal capacities comparable to those of activated carbon for removal of THMs, synthetic organic chemicals (SOCs) such as warfarin (WFN) (anticoagulant pharmaceutical, rodenticide), and naturally occurring trace organics such as the taste-and-odor compound 2-methylisoborneol (cyanobacterial metabolite). Results show chars can be used effectively to remove objectionable tastes and odors related to chlorine and cyanobacteria, DBPs, and SOCs. The use of char may lead to microbial risk reduction through greater acceptance of chlorine-based disinfection due to improved water esthetics, as well as chemical risk reduction associated with DBP and SOC exposure. DA - 2015/// PY - 2015/// DO - 10.2166/washdev.2015.172 VL - 5 IS - 3 SP - 359-372 SN - 2043-9083 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84940023189&partnerID=MN8TOARS KW - adsorption KW - biochar KW - charcoal KW - chemical water contaminants KW - point-of-use water treatment ER - TY - JOUR TI - Influence of C-Trap Ion Accumulation Time on the Detectability of Analytes in IR-MALDESI MSI AU - Rosen, Elias P. AU - Bokhart, Mark T. AU - Nazari, Milad AU - Muddiman, David C. T2 - ANALYTICAL CHEMISTRY AB - Laser desorption followed by post electrospray ionization requires synchronized timing of the key events (sample desorption/ionization, mass spectrometry analysis, and sample translation) necessary to conduct mass spectrometry imaging (MSI) with adequate analyte sensitivity. In infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI analyses, two laser pulses are used for analysis at each volumetric element, or voxel, of a biological sample and ion accumulation in the C-trap exceeding 100 ms is necessary to capture all sample-associated ions using an infrared laser with a 20 Hz repetition rate. When coupled to an Orbitrap-based mass spectrometer like the Q Exactive Plus, this time window for ion accumulation exceeds dynamically controlled trapping of samples with comparable ion flux by Automatic Gain Control (AGC), which cannot be used during MSI analysis. In this work, a next-generation IR-MALDESI source has been designed and constructed that incorporates a mid-infrared OPO laser capable of operating at 100 Hz and allows requisite C-trap inject time during MSI to be reduced to 30 ms. Analyte detectability of the next-generation IR-MALDESI integrated source has been evaluated as a function of laser repetition rate (100-20 Hz) with corresponding C-trap ion accumulation times (30-110 ms) in both untargeted and targeted analysis of biological samples. Reducing the C-trap ion accumulation time resulted in increased ion abundance by up to 3 orders of magnitude for analytes ranging from xenobiotics to endogenous lipids, and facilitated the reduction of voxel-to-voxel variability by more than 3-fold. DA - 2015/10/20/ PY - 2015/10/20/ DO - 10.1021/acs.analchem.5b02641 VL - 87 IS - 20 SP - 10483-10490 SN - 1520-6882 ER - TY - JOUR TI - Feasibility of Using Traditional Kiln Charcoals in Low-Cost Water Treatment: Role of Pyrolysis Conditions on 2,4-D Herbicide Adsorption AU - Kearns, Joshua P. AU - Knappe, Detlef R. U. AU - Summers, R. Scott T2 - ENVIRONMENTAL ENGINEERING SCIENCE AB - Prior research has established that pyrolysis temperature during charcoal production is the primary variable influencing adsorption capacity. The first objective of this work was to monitor thermal conditions during charcoal production within three common traditional kiln models. Then, a programmable laboratory furnace pyrolyzer was used to generate chars from eucalyptus, pine, and longan woods and bamboo under a similar range of thermal conditions as identified in the field study. Using chars produced from the furnace, the second objective of this study was to investigate the influence of biomass feedstock and grain size, peak pyrolysis temperature, and duration of thermal treatment on 2,4-D herbicide sorption capacity. A third objective was to determine if chars produced in the laboratory furnace using thermal profiles similar to those observed in the horizontal drum kiln would exhibit similar adsorbent characteristics to kiln charcoals. Field observations revealed significant variability in temperature profiles during pyrolysis in traditional charcoal kilns, and laboratory experiments indicated corresponding variability in equilibrium 2,4-D uptake from surface water ranging from virtually no adsorption to around 10% of the adsorption capacity of commercial activated carbon. Increasing pyrolysis temperature or duration increased 2,4-D adsorption capacity, whereas feedstock did not affect adsorption capacity for the materials studied. Similar herbicide adsorption capacity was observed for furnace chars and kiln charcoals generated using similar thermal profiles. The difficulty of achieving precise temperature control with traditional charcoal production systems contributes to wide thermal variability within and between batches, which translates to wide variability in adsorption of organic compounds. DA - 2015/11/1/ PY - 2015/11/1/ DO - 10.1089/ees.2015.0243 VL - 32 IS - 11 SP - 912-921 SN - 1557-9018 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84946830926&partnerID=MN8TOARS KW - 2,4-D KW - adsorption KW - biochar KW - charcoal KW - decentralized water treatment KW - engineering for developing communities KW - low cost adsorbents ER - TY - JOUR TI - Cancer incidence and metolachlor use in the Agricultural Health Study: An update AU - Silver, Sharon R. AU - Bertke, Steven J. AU - Hines, Cynthia J. AU - Alavanja, Michael C.R. AU - Hoppin, Jane A. AU - Lubin, Jay H. AU - Rusiecki, Jennifer A. AU - Sandler, Dale P. AU - Beane Freeman, Laura E. T2 - International Journal of Cancer AB - Metolachlor, a widely used herbicide, is classified as a Group C carcinogen by the U.S. Environmental Protection Agency based on increased liver neoplasms in female rats. Epidemiologic studies of the health effects of metolachlor have been limited. The Agricultural Health Study (AHS) is a prospective cohort study including licensed private and commercial pesticide applicators in Iowa and North Carolina enrolled 1993-1997. We evaluated cancer incidence through 2010/2011 (NC/IA) for 49,616 applicators, 53% of whom reported ever using metolachlor. We used Poisson regression to evaluate relations between two metrics of metolachlor use (lifetime days, intensity-weighted lifetime days) and cancer incidence. We saw no association between metolachlor use and incidence of all cancers combined (n = 5,701 with a 5-year lag) or most site-specific cancers. For liver cancer, in analyses restricted to exposed workers, elevations observed at higher categories of use were not statistically significant. However, trends for both lifetime and intensity-weighted lifetime days of metolachor use were positive and statistically significant with an unexposed reference group. A similar pattern was observed for follicular cell lymphoma, but no other lymphoma subtypes. An earlier suggestion of increased lung cancer risk at high levels of metolachlor use in this cohort was not confirmed in this update. This suggestion of an association between metolachlor and liver cancer among pesticide applicators is a novel finding and echoes observation of increased liver neoplasms in some animal studies. However, our findings for both liver cancer and follicular cell lymphoma warrant follow-up to better differentiate effects of metolachlor use from other factors. DA - 2015/6/25/ PY - 2015/6/25/ DO - 10.1002/ijc.29621 VL - 137 IS - 11 SP - 2630-2643 J2 - Int. J. Cancer LA - en OP - SN - 0020-7136 UR - http://dx.doi.org/10.1002/ijc.29621 DB - Crossref KW - cancer KW - epidemiology KW - pesticide KW - occupation ER - TY - JOUR TI - Predicting characteristics of rainfall driven estrogen runoff and transport from swine AFO spray fields AU - Lee, Boknam AU - Kullman, Sethw. AU - Yost, Erin E. AU - Meyer, Michael T. AU - Worley-Davis, Lynn AU - Williams, C. Michael AU - Reckhow, Kenneth H. T2 - SCIENCE OF THE TOTAL ENVIRONMENT AB - Animal feeding operations (AFOs) have been implicated as potentially major sources of estrogenic contaminants into the aquatic environment due to the relatively minimal treatment of waste and potential mobilization and transport of waste components from spray fields. In this study a Bayesian network (BN) model was developed to inform management decisions and better predict the transport and fate of natural steroidal estrogens from these sites. The developed BN model integrates processes of surface runoff and sediment loss with the modified universal soil loss equation (MUSLE) and the soil conservation service curve number (SCS-CN) runoff model. What-if scenario simulations of lagoon slurry wastes to the spray fields were conducted for the most abundant natural estrogen estrone (E1) observed in the system. It was found that E1 attenuated significantly after 2 months following waste slurry application in both spring and summer seasons, with the overall attenuation rate predicted to be higher in the summer compared to the spring. Using simulations of rainfall events in conjunction with waste slurry application rates, it was predicted that the magnitude of E1 runoff loss is significantly higher in the spring as compared to the summer months, primarily due to spray field crop management plans. Our what-if scenario analyses suggest that planting Bermuda grass in the spray fields is likely to reduce runoff losses of natural estrogens near the water bodies and ecosystems, as compared to planting of soybeans. DA - 2015/11/1/ PY - 2015/11/1/ DO - 10.1016/j.scitotenv.2015.06.051 VL - 532 SP - 571-580 SN - 1879-1026 KW - Estrogen runoff and transport KW - Bayesian network model KW - Swine animal feeding operation KW - Spray fields ER - TY - JOUR TI - Pesticide exposure and end-stage renal disease risk among wives of pesticide applicators in the Agricultural Health Study AU - Lebov, Jill F. AU - Engel, Lawrence S. AU - Richardson, David AU - Hogan, Susan L. AU - Sandler, Dale P. AU - Hoppin, Jane A. T2 - Environmental Research AB - Pesticide exposure has been found to cause renal damage and dysfunction in experimental studies, but epidemiological research on the renal effects of chronic low-level pesticide exposure is limited. We investigated the relationships between end-stage renal disease (ESRD) among wives of licensed pesticide applicators (N=31,142) in the Agricultural Health Study (AHS) and (1) personal pesticide use, (2) exposure to the husband's pesticide use, and (3) other pesticide-associated farming and household activities. AHS participants reported pesticide exposure via self-administered questionnaires at enrollment (1993–1997). ESRD cases were identified via linkage to the United States Renal Data System. Associations between ESRD and pesticide exposures were estimated with Cox proportional hazard regression models controlling for age at enrollment. Models of associations with farming and household factors were additionally adjusted for personal use of pesticides. We identified 98 ESRD cases diagnosed between enrollment and 31 December 2011. Although women who ever applied pesticides (56% of cohort) were less likely than those who did not apply to develop ESRD (Hazard Ratio (HR): 0.42; 95% CI: 0.28, 0.64), among women who did apply pesticides, the rate of ESRD was significantly elevated among those who reported the highest (vs. lowest) cumulative general pesticide use (HR: 4.22; 95% CI: 1.26, 14.20). Among wives who never applied pesticides, ESRD was associated with husbands' ever use of paraquat (HR=1.99; 95% CI: 1.14, 3.47) and butylate (HR=1.71; 95% CI: 1.00, 2.95), with a positive exposure–response pattern for husband’s cumulative use of these pesticides. ESRD may be associated with direct and/or indirect exposure to pesticides among farm women. Future studies should evaluate indirect exposure risk among other rural populations. DA - 2015/11// PY - 2015/11// DO - 10.1016/j.envres.2015.10.002 VL - 143 SP - 198-210 J2 - Environmental Research LA - en OP - SN - 0013-9351 UR - http://dx.doi.org/10.1016/j.envres.2015.10.002 DB - Crossref KW - Pesticide exposure KW - End-stage renal disease KW - Farm women KW - Agricultural exposures ER - TY - JOUR TI - Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study AU - Lerro, Catherine C AU - Koutros, Stella AU - Andreotti, Gabriella AU - Friesen, Melissa C AU - Alavanja, Michael C AU - Blair, Aaron AU - Hoppin, Jane A AU - Sandler, Dale P AU - Lubin, Jay H AU - Ma, Xiaomei AU - Zhang, Yawei AU - Beane Freeman, Laura E T2 - Occupational and Environmental Medicine AB -

Objectives

Organophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. We evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort.

Methods

At enrolment (1993–1997), spouses provided information about ever use of specific pesticides, including 10 OPs, demographic information, reproductive health history and other potential confounders. We used Poisson regression to estimate relative risks (RRs) and 95% CIs for all cancers diagnosed through 2010 for North Carolina and through 2011 for Iowa.

Results

Among 30 003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR=1.20, 95% CI 1.01 to 1.43). Malathion, the most commonly reported OP, was associated with increased risk of thyroid cancer (RR=2.04, 95% CI 1.14 to 3.63) and decreased risk of non-Hodgkin lymphoma (RR=0.64, 95% CI 0.41 to 0.99). Diazinon use was associated with ovarian cancer (RR=1.87, 95% CI 1.02 to 3.43).

Conclusions

We observed increased risk with OP use for several hormonally-related cancers, including breast, thyroid and ovary, suggesting potential for hormonally-mediated effects. This study represents the first comprehensive analysis of OP use and cancer risk among women, and thus demonstrates a need for further evaluation. DA - 2015/7/6/ PY - 2015/7/6/ DO - 10.1136/oemed-2014-102798 VL - 72 IS - 10 SP - 736-744 J2 - Occup Environ Med LA - en OP - SN - 1351-0711 1470-7926 UR - http://dx.doi.org/10.1136/oemed-2014-102798 DB - Crossref ER - TY - JOUR TI - In-depth LC-MS/MS analysis of the chicken ovarian cancer proteome reveals conserved and novel differentially regulated proteins in humans AU - Nepomuceno, Angelito I. AU - Shao, Huanjie AU - Jing, Kai AU - Ma, Yibao AU - Petitte, James N. AU - Idowu, Michael O. AU - Muddiman, David C. AU - Fang, Xianjun AU - Hawkridge, Adam M. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY AB - Ovarian cancer (OVC) remains the most lethal gynecological malignancy in the world due to the combined lack of early-stage diagnostics and effective therapeutic strategies. The development and application of advanced proteomics technology and new experimental models has created unique opportunities for translational studies. In this study, we investigated the ovarian cancer proteome of the chicken, an emerging experimental model of OVC that develops ovarian tumors spontaneously. Matched plasma, ovary, and oviduct tissue biospecimens derived from healthy, early-stage OVC, and late-stage OVC birds were quantitatively characterized by label-free proteomics. Over 2600 proteins were identified in this study, 348 of which were differentially expressed by more than twofold (p ≤ 0.05) in early- and late-stage ovarian tumor tissue specimens relative to healthy ovarian tissues. Several of the 348 proteins are known to be differentially regulated in human cancers including B2M, CLDN3, EPCAM, PIGR, S100A6, S100A9, S100A11, and TPD52. Of particular interest was ovostatin 2 (OVOS2), a novel 165-kDa protease inhibitor found to be strongly upregulated in chicken ovarian tumors (p = 0.0005) and matched plasma (p = 0.003). Indeed, RT-quantitative PCR and Western blot analysis demonstrated that OVOS2 mRNA and protein were also upregulated in multiple human OVC cell lines compared to normal ovarian epithelia (NOE) cells and immunohistochemical staining confirmed overexpression of OVOS2 in primary human ovarian cancers relative to non-cancerous tissues. Collectively, these data provide the first evidence for involvement of OVOS2 in the pathogenesis of both chicken and human ovarian cancer. DA - 2015/9// PY - 2015/9// DO - 10.1007/s00216-015-8862-4 VL - 407 IS - 22 SP - 6851-6863 SN - 1618-2650 KW - Mass spectrometry KW - Proteomics KW - Ovarian Cancer KW - Chicken KW - Ovostatin 2 KW - OVOS2 ER - TY - JOUR TI - Global Proteomic Analysis of Functional Compartments in Immature Avian Follicles Using Laser Microdissection Coupled to LC-MS/MS AU - Nepomuceno, Angelito I. AU - Muddiman, David C. AU - Petitte, James N. T2 - JOURNAL OF PROTEOME RESEARCH AB - Laser microdissection (LMD) was utilized for the separation of the yolk, follicular wall (granulosa and theca), and surrounding stromal cells of small white follicles (SWF) obtained from reproductively active domestic fowl. Herein, we provide an in situ proteomics-based approach to studying follicular development through the use of LMD and mass spectrometry. This study resulted in a total of 2889 proteins identified from the three specific isolated compartments. White yolk from the smallest avian follicles resulted in the identification of 1984 proteins, while isolated follicular wall and ovarian stroma yielded 2470 and 2456 proteins, respectively. GO annotations highlighted the functional differences between the compartments. Among the three compartments examined, the relative abundance of vitellogenins, steroidogenic enzymes, anti-Mullerian hormone, transcription factors, and proteins involved in retinoic acid receptors/retinoic acid synthesis, transcription factors, and cell surface receptors such as EGFR and their associated signaling pathways reflected known cellular function of the ovary. This study has provided a global proteome for SWF, white yolk, and ovarian stroma of the avian ovary that can be used as a baseline for future studies and verifies that the coupling of LMD with proteomic analysis can be used to evaluate proteins from small, physiologically functional compartments of complex tissue. DA - 2015/9// PY - 2015/9// DO - 10.1021/acs.jproteome.5b00346 VL - 14 IS - 9 SP - 3912-3923 SN - 1535-3907 KW - microdissection KW - proteomics KW - ovary KW - follicle KW - avian KW - chicken KW - yolk KW - steroidogenesis KW - vitellogenin ER - TY - JOUR TI - Decomposition and carbon storage of selected paper products in laboratory-scale landfills AU - Wang, Xiaoming AU - Cruz, Florentino B. AU - Ximenes, Fabiano AU - Barlaz, Morton A. T2 - SCIENCE OF THE TOTAL ENVIRONMENT AB - The objective of this study was to measure the anaerobic biodegradation of different types of paper products in laboratory-scale landfill reactors. The study included (a) measurement of the loss of cellulose, hemicellulose, organic carbon, and (b) measurement of the methane yields for each paper product. The test materials included two samples each of newsprint (NP), copy paper (CP), and magazine paper (MG), and one sample of diaper (DP). The methane yields, carbon storage factors and the extent of cellulose and hemicellulose decomposition all consistently show that papers made from mechanical pulps (e.g., NPs) are less degradable than those made from chemical pulps where essentially all lignin was chemically removed (e.g., CPs). The diaper, which is not only made from chemical pulp but also contains some gel and plastic, exhibited limited biodegradability. The extent of biogenic carbon conversion varied from 21 to 96% among papers, which contrasts with the uniform assumption of 50% by the Intergovernmental Panel on Climate Change (IPCC) for all degradable materials discarded in landfills. Biochemical methane potential tests also showed that the solids to liquid ratio used in the test can influence the results. DA - 2015/11/1/ PY - 2015/11/1/ DO - 10.1016/j.scitotenv.2015.05.132 VL - 532 SP - 70-79 SN - 1879-1026 KW - Landfills KW - Municipal solid waste KW - Paper products KW - Anaerobic decomposition KW - Biochemical methane potential KW - Carbon storage ER - TY - JOUR TI - A nonclassical MHC class I U lineage locus in zebrafish with a null haplotypic variant AU - Dirscherl, Hayley AU - Yoder, Jeffrey A. T2 - Immunogenetics AB - Three sequence lineages of MHC class I genes have been described in zebrafish (Danio rerio): U, Z, and L. The U lineage genes encoded on zebrafish chromosome 19 are predicted to provide the classical function of antigen presentation. This MHC class I locus displays significant haplotypic variation and is the only MHC class I locus in zebrafish that shares conserved synteny with the core mammalian MHC. Here, we describe two MHC class I U lineage genes, mhc1ula and mhc1uma, that map to chromosome 22. Unlike the U lineage proteins encoded on chromosome 19, Ula and Uma likely play a nonclassical role as they lack conservation of key peptide binding residues, display limited polymorphic variation, and exhibit tissue-specific expression. We also describe a null haplotype at this chromosome 22 locus in which the mhc1ula and mhc1uma genes are absent due to a ~30 kb deletion with no other MHC class I sequences present. Functional and non-functional transcripts of mhc1ula and mhc1uma were identified; however, mhc1uma transcripts were often not amplified or amplified at low levels from individuals possessing an apparently bona fide gene. These distinct U lineage genes may be restricted to the superorder Ostariophysi as similar sequences only could be identified from the blind cavefish (Astyanax mexicanus), fathead minnow (Pimephales promelas), goldfish (Carassius auratus), and grass carp (Ctenopharyngodon idella). DA - 2015/8/9/ PY - 2015/8/9/ DO - 10.1007/s00251-015-0862-1 VL - 67 IS - 9 SP - 501-513 J2 - Immunogenetics LA - en OP - SN - 0093-7711 1432-1211 UR - http://dx.doi.org/10.1007/s00251-015-0862-1 DB - Crossref KW - Teleost KW - MHC class I KW - Evolution KW - Polymorphism KW - Haplotype ER - TY - JOUR TI - Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples AU - Hecht, Elizabeth S. AU - Scholl, Elizabeth H. AU - Walker, S. Hunter AU - Taylor, Amber D. AU - Cliby, William A. AU - Motsinger-Reif, Alison A. AU - Muddiman, David C. T2 - JOURNAL OF PROTEOME RESEARCH AB - An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. Aberrant glycosylation by OVC has been reported, but studies have yet to identify an N-glycan with sufficiently high specificity. We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I-IV, respectively. For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. DA - 2015/10// PY - 2015/10// DO - 10.1021/acs.jproteome.5b00703 VL - 14 IS - 10 SP - 4394-4401 SN - 1535-3907 KW - N-linked glycosylation KW - INLIGHT KW - ovarian cancer KW - relative quantification KW - cancer biomarker KW - human plasma ER - TY - JOUR TI - Pred-hERG: A Novel web-Accessible Computational Tool for Predicting Cardiac Toxicity AU - Braga, Rodolpho C. AU - Alves, Vinicius M. AU - Silva, Meryck F. B. AU - Muratov, Eugene AU - Fourches, Denis AU - Liao, Luciano M. AU - Tropsha, Alexander AU - Andrade, Carolina H. T2 - MOLECULAR INFORMATICS AB - The blockage of the hERG K(+) channels is closely associated with lethal cardiac arrhythmia. The notorious ligand promiscuity of this channel earmarked hERG as one of the most important antitargets to be considered in early stages of drug development process. Herein we report on the development of an innovative and freely accessible web server for early identification of putative hERG blockers and non-blockers in chemical libraries. We have collected the largest publicly available curated hERG dataset of 5,984 compounds. We succeed in developing robust and externally predictive binary (CCR≈0.8) and multiclass models (accuracy≈0.7). These models are available as a web-service freely available for public at http://labmol.farmacia.ufg.br/predherg/. Three following outcomes are available for the users: prediction by binary model, prediction by multi-class model, and the probability maps of atomic contribution. The Pred-hERG will be continuously updated and upgraded as new information became available. DA - 2015/10// PY - 2015/10// DO - 10.1002/minf.201500040 VL - 34 IS - 10 SP - 698-701 SN - 1868-1751 KW - hERG KW - QSAR models KW - web-Server KW - Screening ER - TY - JOUR TI - Mechanisms of Egg Yolk Formation and Implications on Early Life History of White Perch (Morone americana) AU - Schilling, Justin AU - Loziuk, Philip L. AU - Muddiman, David C. AU - Daniels, Harry V. AU - Reading, Benjamin J. T2 - PLOS ONE AB - The three white perch (Morone americana) vitellogenins (VtgAa, VtgAb, VtgC) were quantified accurately and precisely in the liver, plasma, and ovary during pre-, early-, mid-, and post-vitellogenic oocyte growth using protein cleavage-isotope dilution mass spectrometry (PC-IDMS). Western blotting generally mirrored the PC-IDMS results. By PC-IDMS, VtgC was quantifiable in pre-vitellogenic ovary tissues and VtgAb was quantifiable in pre-vitellogenic liver tissues however, neither protein was detected by western blotting in these respective tissues at this time point. Immunohistochemistry indicated that VtgC was present within pre-vitellogenic oocytes and localized to lipid droplets within vitellogenic oocytes. Affinity purification coupled to tandem mass spectrometry using highly purified VtgC as a bait protein revealed a single specific interacting protein (Y-box binding protein 2a-like [Ybx2a-like]) that eluted with suramin buffer and confirmed that VtgC does not bind the ovary vitellogenin receptors (LR8 and Lrp13). Western blotting for LR8 and Lrp13 showed that both receptors were expressed during vitellogenesis with LR8 and Lrp13 expression highest in early- and mid-vitellogenesis, respectively. The VtgAa within the ovary peaked during post-vitellogenesis, while VtgAb peaked during early-vitellogenesis in both white perch and the closely related striped bass (M. saxatilis). The VtgC was steadily accumulated by oocytes beginning during pre-vitellogenesis and continued until post-vitellogenesis and its composition varies widely between striped bass and white perch. In striped bass, the VtgC accounted for 26% of the vitellogenin-derived egg yolk, however in the white perch it comprised only 4%. Striped bass larvae have an extended developmental window and these larvae have yolk stores that may enable them to survive in the absence of food for twice as long as white perch after hatch. Thus, the VtgC may play an integral role in providing nutrients to late stage fish larvae prior to the onset of exogenous feeding and its composition in the egg yolk may relate to different early life histories among this diverse group of animals. DA - 2015/11/18/ PY - 2015/11/18/ DO - 10.1371/journal.pone.0143225 VL - 10 IS - 11 SP - SN - 1932-6203 ER - TY - JOUR TI - Elucidation of Xylem-Specific Transcription Factors and Absolute Quantification of Enzymes Regulating Cellulose Biosynthesis in Populus trichocarpa AU - Loziuk, Philip L. AU - Parker, Jennifer AU - Li, Wei AU - Lin, Chien-Yuan AU - Wang, Jack P. AU - Li, Quanzi AU - Sederoff, Ronald R. AU - Chiang, Vincent L. AU - Muddiman, David C. T2 - JOURNAL OF PROTEOME RESEARCH AB - Cellulose, the main chemical polymer of wood, is the most abundant polysaccharide in nature.1 The ability to perturb the abundance and structure of cellulose microfibrils is of critical importance to the pulp and paper industry as well as for the textile, wood products, and liquid biofuels industries. Although much has been learned at the transcript level about the biosynthesis of cellulose, a quantitative understanding at the proteome level has yet to be established. The study described herein sought to identify the proteins directly involved in cellulose biosynthesis during wood formation in Populus trichocarpa along with known xylem-specific transcription factors involved in regulating these key proteins. Development of an effective discovery proteomic strategy through a combination of subcellular fractionation of stem differentiating xylem tissue (SDX) with recently optimized FASP digestion protocols, StageTip fractionation, as well as optimized instrument parameters for global proteomic analysis using the quadrupole-orbitrap mass spectrometer resulted in the deepest proteomic coverage of SDX protein from P. trichocarpa with 9,146 protein groups being identified (1% FDR). Of these, 20 cellulosic/hemicellulosic enzymes and 43 xylem-specific transcription factor groups were identified. Finally, selection of surrogate peptides led to an assay for absolute quantification of 14 cellulosic proteins in SDX of P. trichocarpa. DA - 2015/10// PY - 2015/10// DO - 10.1021/acs.jproteome.5b00233 VL - 14 IS - 10 SP - 4158-4168 SN - 1535-3907 KW - shotgun discovery proteomics KW - absolute quantification KW - PC-IDMS KW - cellulose biosynthesis KW - transcription factor KW - targeted mass spectrometiry KW - SRM ER - TY - JOUR TI - The decay of wood in landfills in contrasting climates in Australia AU - Ximenes, Fabiano AU - Bjordal, Charlotte AU - Cowie, Annette AU - Barlaz, Morton T2 - WASTE MANAGEMENT AB - Wood products in landfill are commonly assumed to decay within several decades, returning the carbon contained therein to the atmosphere, with about half the carbon released as methane. However, the rate and extent of decay is not well known, as very few studies have examined the decay of wood products in landfills. This study reports on the findings from landfill excavations conducted in the Australian cities of Sydney and Cairns located in temperate and tropical environments, respectively. The objective of this study was to determine whether burial of the wood in warmer, more tropical conditions in Cairns would result in greater levels of decay than occurs in the temperate environment of Sydney. Wood samples recovered after 16–44 years in landfill were examined through physical, chemical and microscopic analyses, and compared with control samples to determine the carbon loss. There was typically little or no decay in the wood samples analysed from the landfill in Sydney. Although there was significant decay in rainforest wood species excavated from Cairns, decay levels for wood types that were common to both Cairns and Sydney landfills were similar. The current Intergovernmental Panel on Climate Change (IPCC, 2006) default decay factor for organic materials in landfills is 50%. In contrast, the carbon loss determined for Pinus radiata recovered from Sydney and Cairns landfills was 7.9% and 4.4%, respectively, and 0% for Agathis sp. This suggests that climate did not influence decay, and that the more extensive levels of decay observed for some wood samples from Cairns indicates that those wood types were more susceptible to biodegradation. Microscopic analyses revealed that most decay patterns observed in samples analysed from Sydney were consistent with aerobic fungal decay. Only a minor portion of the microbial decay was due to erosion bacteria active in anaerobic/near anaerobic environments. The findings of this study strongly suggest that models that adopt current accepted default factors for the decay of wood in landfills greatly overestimate methane emissions. DA - 2015/7// PY - 2015/7// DO - 10.1016/j.wasman.2015.03.032 VL - 41 SP - 101-110 SN - 0956-053X KW - Wood KW - Decay KW - Landfill KW - Climate KW - Carbon KW - Methane ER - TY - JOUR TI - Physical and Biological Release of Poly- and Perfluoroalkyl Substances (PFASs) from Municipal Solid Waste in Anaerobic Model Landfill Reactors AU - Allred, B. McKay AU - Lang, Johnsie R. AU - Barlaz, Morton A. AU - Field, Jennifer A. T2 - ENVIRONMENTAL SCIENCE & TECHNOLOGY AB - A wide variety of consumer products that are treated with poly- and perfluoroalkyl substances (PFASs) and related formulations are disposed of in landfills. Landfill leachate has significant concentrations of PFASs and acts as secondary point sources to surface water. This study models how PFASs enter leachate using four laboratory-scale anaerobic bioreactors filled with municipal solid waste (MSW) and operated over 273 days. Duplicate reactors were monitored under live and abiotic conditions to evaluate influences attributable to biological activity. The biologically active reactors simulated the methanogenic conditions that develop in all landfills, producing ∼140 mL CH4/dry g refuse. The average total PFAS leaching measured in live reactors (16.7 nmol/kg dry refuse) was greater than the average for abiotic reactors (2.83 nmol/kg dry refuse), indicating biological processes were primarily responsible for leaching. The low-level leaching in the abiotic reactors was primarily due to PFCAs ≤C8 (2.48 nmol/kg dry refuse). Concentrations of known biodegradation intermediates, including methylperfluorobutane sulfonamide acetic acid and the n:2 and n:3 fluorotelomer carboxylates, increased steadily after the onset of methanogenesis, with the 5:3 fluorotelomer carboxylate becoming the single most concentrated PFAS observed in live reactors (9.53 nmol/kg dry refuse). DA - 2015/7/7/ PY - 2015/7/7/ DO - 10.1021/acs.est.5b01040 VL - 49 IS - 13 SP - 7648-7656 SN - 1520-5851 ER - TY - JOUR TI - Pesticide Use and Relative Leukocyte Telomere Length in the Agricultural Health Study AU - Andreotti, Gabriella AU - Hoppin, Jane A. AU - Hou, Lifang AU - Koutros, Stella AU - Gadalla, Shahinaz M. AU - Savage, Sharon A. AU - Lubin, Jay AU - Blair, Aaron AU - Hoxha, Mirjam AU - Baccarelli, Andrea AU - Sandler, Dale AU - Alavanja, Michael AU - Beane Freeman, Laura E. T2 - PLOS ONE AB - Some studies suggest that telomere length (TL) may be influenced by environmental exposures, including pesticides. We examined associations between occupational pesticide use reported at three time points and relative telomere length (RTL) in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators in Iowa and North Carolina. RTL was measured by qPCR using leukocyte DNA from 568 cancer-free male AHS participants aged 31-94 years with blood samples collected between 2006 and 2008. Self-reported information, including pesticide use, was collected at three time points: enrollment (1993-1997) and two follow-up questionnaires (1998-2003, 2005-2008). For each pesticide, we evaluated cumulative use (using data from all three questionnaires), and more recent use (using data from the last follow-up questionnaire). Multivariable linear regression was used to examine the associations between pesticide use (ever, lifetime days, intensity-weighted lifetime days (lifetime days*intensity score)) and RTL, adjusting for age at blood draw and use of other pesticides. Of the 57 pesticides evaluated with cumulative use, increasing lifetime days of 2,4-D (p-trend=0.001), diazinon (p-trend=0.002), and butylate (p-trend=0.01) were significantly associated with shorter RTL, while increasing lifetime days of alachlor was significantly associated with longer RTL (p-trend=0.03). Only the association with 2,4-D was significant after adjustment for multiple comparisons. Of the 40 pesticides evaluated for recent use, malathion was associated with shorter RTL (p=0.03), and alachlor with longer RTL (p=0.03). Our findings suggest that leukocyte TL may be impacted by cumulative use and recent use of certain pesticides. DA - 2015/7/21/ PY - 2015/7/21/ DO - 10.1371/journal.pone.0133382 VL - 10 IS - 7 SP - e0133382 J2 - PLoS ONE LA - en OP - SN - 1932-6203 UR - http://dx.doi.org/10.1371/journal.pone.0133382 DB - Crossref ER - TY - JOUR TI - Molecular Cloning, Functional Characterization, and Evolutionary Analysis of Vitamin D Receptors Isolated from Basal Vertebrates AU - Kollitz, Erin M. AU - Zhang, Guozhu AU - Hawkins, Mary Beth AU - Whitfield, G. Kerr AU - Reif, David M. AU - Kullman, Seth W. T2 - PLOS ONE AB - The vertebrate genome is a result of two rapid and successive rounds of whole genome duplication, referred to as 1R and 2R. Furthermore, teleost fish have undergone a third whole genome duplication (3R) specific to their lineage, resulting in the retention of multiple gene paralogs. The more recent 3R event in teleosts provides a unique opportunity to gain insight into how genes evolve through specific evolutionary processes. In this study we compare molecular activities of vitamin D receptors (VDR) from basal species that diverged at key points in vertebrate evolution in order to infer derived and ancestral VDR functions of teleost paralogs. Species include the sea lamprey (Petromyzon marinus), a 1R jawless fish; the little skate (Leucoraja erinacea), a cartilaginous fish that diverged after the 2R event; and the Senegal bichir (Polypterus senegalus), a primitive 2R ray-finned fish. Saturation binding assays and gel mobility shift assays demonstrate high affinity ligand binding and classic DNA binding characteristics of VDR has been conserved across vertebrate evolution. Concentration response curves in transient transfection assays reveal EC50 values in the low nanomolar range, however maximum transactivational efficacy varies significantly between receptor orthologs. Protein-protein interactions were investigated using co-transfection, mammalian 2-hybrid assays, and mutations of coregulator activation domains. We then combined these results with our previous study of VDR paralogs from 3R teleosts into a bioinformatics analysis. Our results suggest that 1, 25D3 acts as a partial agonist in basal species. Furthermore, our bioinformatics analysis suggests that functional differences between VDR orthologs and paralogs are influenced by differential protein interactions with essential coregulator proteins. We speculate that we may be observing a change in the pharmacodynamics relationship between VDR and 1, 25D3 throughout vertebrate evolution that may have been driven by changes in protein-protein interactions between VDR and essential coregulators. DA - 2015/4/9/ PY - 2015/4/9/ DO - 10.1371/journal.pone.0122853 VL - 10 IS - 4 SP - SN - 1932-6203 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84929469049&partnerID=MN8TOARS ER - TY - JOUR TI - Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans AU - Hecht, Elizabeth S. AU - McCord, James P. AU - Muddiman, David C. T2 - ANALYTICAL CHEMISTRY AB - High-throughput, quantitative processing of N-linked glycans would facilitate large-scale studies correlating the glycome with disease and open the field to basic and applied researchers. We sought to meet these goals by coupling filter-aided-N-glycan separation (FANGS) to the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) for analysis of plasma. A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. We demonstrate that FANGS–INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. Furthermore, to increase the depth of glycome coverage, we executed a definitive screening design of experiments (DOE) to optimize the MS parameters for glycan analyses. We optimized MS parameters across five N-glycan responses using a standard glycan mixture, translated these to plasma and achieved up to a 3-fold increase in ion abundances. DA - 2015/7/21/ PY - 2015/7/21/ DO - 10.1021/acs.analchem.5b01609 VL - 87 IS - 14 SP - 7305-7312 SN - 1520-6882 ER - TY - PCOMM TI - Curation of chemogenomics data AU - Fourches, Denis AU - Muratov, Eugene AU - Tropsha, Alexander DA - 2015/8// PY - 2015/8// DO - 10.1038/nchembio.1881 SP - 535-535 ER - TY - JOUR TI - Long noncoding RNA lincRNA-p21 is the major mediator of UVB-induced and p53-dependent apoptosis in keratinocytes AU - Hall, J. R. AU - Messenger, Z. J. AU - Tam, H. W. AU - Phillips, S. L. AU - Recio, L. AU - Smart, R. C. T2 - CELL DEATH & DISEASE AB - Abstract LincRNA-p21 is a long noncoding RNA and a transcriptional target of p53 and HIF-1α. LincRNA-p21 regulates gene expression in cis and trans , mRNA translation, protein stability, the Warburg effect, and p53-dependent apoptosis and cell cycle arrest in doxorubicin-treated mouse embryo fibroblasts. p53 plays a key role in the response of skin keratinocytes to UVB-induced DNA damage by inducing cell cycle arrest and apoptosis. In skin cancer development, UVB-induced mutation of p53 allows keratinocytes upon successive UVB exposures to evade apoptosis and cell cycle arrest. We hypothesized that lincRNA-p21 has a key functional role in UVB-induced apoptosis and/or cell cycle arrest in keratinocytes and loss of lincRNA-p21 function results in the evasion of apoptosis and/or cell cycle arrest. We observed that lincRNA-p21 transcripts are highly inducible by UVB in mouse and human keratinocytes in culture and in mouse skin in vivo . LincRNA-p21 is regulated at the transcriptional level in response to UVB, and the UVB induction of lincRNA-p21 in keratinocytes and in vivo in mouse epidermis is primarily through a p53-dependent pathway. Knockdown of lincRNA-p21 blocked UVB-induced apoptosis in mouse and human keratinocytes, and lincRNA-p21 was responsible for the majority of UVB-induced and p53-mediated apoptosis in keratinocytes. Knockdown of lincRNA-p21 had no effect on cell proliferation in untreated or UVB-treated keratinocytes. An early event in skin cancer is the mutation of a single p53 allele. We observed that a mutant p53 +/R172H allele expressed in mouse epidermis (K5Cre +/tg ;LSLp53 +/R172H ) showed a significant dominant-negative inhibitory effect on UVB-induced lincRNA-p21 transcription and apoptosis in epidermis. We conclude lincRNA-p21 is highly inducible by UVB and has a key role in triggering UVB-induced apoptotic death. We propose that the mutation of a single p53 allele provides a pro-oncogenic function early in skin cancer development through a dominant inhibitory effect on UVB-induced lincRNA-p21 expression and the subsequent evasion of UVB-induced apoptosis. DA - 2015/3// PY - 2015/3// DO - 10.1038/cddis.2015.67 VL - 6 SP - SN - 2041-4889 ER - TY - JOUR TI - Investigating landfill leachate as a source of trace organic pollutants AU - Clarke, Bradley O. AU - Anumol, Tarun AU - Barlaz, Morton AU - Snyder, Shane A. T2 - CHEMOSPHERE AB - Landfill leachate samples (n=11) were collected from five USA municipal solid waste (MSW) landfills and analyzed for ten trace organic pollutants that are commonly detected in surface and municipal wastewater effluents (viz., carbamazepine, DEET, fluoxetine, gemfibrozil, PFOA, PFOS, primidone, sucralose, sulfamethoxazole and trimethoprim). Carbamazepine, DEET, PFOA and primidone were detected in all leachate samples analyzed and gemfibrozil was detected in samples from four of the five-landfill sites. The contaminants found in the highest concentrations were DEET (6900-143000 ng L(-1)) and sucralose (<10-621000 ng L(-1)). Several compounds were not detected (fluoxetine) or detected infrequently (sulfamethoxazole, trimethoprim and PFOS). Using the average mass of DEET in leachate amongst the five landfills and scaling the mass release from the five test landfills to the USA population of landfills, an order of magnitude estimate is that over 10000 kg DEET yr(-1) may be released in leachate. Some pharmaceuticals have similar annual mean discharges to one another, with the estimated annual discharge of carbamazepine, gemfibrozil, primidone equating to 53, 151 and 128 kg year(-1). To the authors knowledge, this is the first time that primidone has been included in a landfill leachate study. While the estimates developed in this study are order of magnitude, the values do suggest the need for further research to better quantify the amount of chemicals sent to wastewater treatment facilities with landfill leachate, potential impacts on treatment processes and the significance of landfill leachate as a source of surface water contamination. DA - 2015/5// PY - 2015/5// DO - 10.1016/j.chemosphere.2015.02.030 VL - 127 SP - 269-275 SN - 1879-1298 KW - Landfill leachate KW - Contaminants of emerging concern KW - DEET KW - Sucralose KW - Primidone ER - TY - JOUR TI - Influence of Desorption Conditions on Analyte Sensitivity and Internal Energy in Discrete Tissue or Whole Body Imaging by IR-MALDESI AU - Rosen, Elias P. AU - Bokhart, Mark T. AU - Ghashghaei, H. Troy AU - Muddiman, David C. T2 - JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY AB - Analyte signal in a laser desorption/postionization scheme such as infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is strongly coupled to the degree of overlap between the desorbed plume of neutral material from a sample and an orthogonal electrospray. In this work, we systematically examine the effect of desorption conditions on IR-MALDESI response to pharmaceutical drugs and endogenous lipids in biological tissue using a design of experiments approach. Optimized desorption conditions have then been used to conduct an untargeted lipidomic analysis of whole body sagittal sections of neonate mouse. IR-MALDESI response to a wide range of lipid classes has been demonstrated, with enhanced lipid coverage received by varying the laser wavelength used for mass spectrometry imaging (MSI). Targeted MS(2) imaging (MS(2)I) of an analyte, cocaine, deposited beneath whole body sections allowed determination of tissue-specific ion response factors, and CID fragments of cocaine were monitored to comment on wavelength-dependent internal energy deposition based on the "survival yield" method. DA - 2015/6// PY - 2015/6// DO - 10.1007/s13361-015-1114-1 VL - 26 IS - 6 SP - 899-910 SN - 1879-1123 KW - IR-MALDESI KW - Mass spectrometry imaging KW - Laser desorption whole body imaging KW - Lipids KW - Xenobiotics ER - TY - JOUR TI - Activin/Nodal Signaling Switches the Terminal Fate of Human Embryonic Stem Cell-derived Trophoblasts AU - Sarkar, Prasenjit AU - Randall, Shan M. AU - Collier, Timothy S. AU - Nero, Anthony AU - Russell, Teal A. AU - Muddiman, David C. AU - Rao, Balaji M. T2 - JOURNAL OF BIOLOGICAL CHEMISTRY AB - Human embryonic stem cells (hESCs) have been routinely treated with bone morphogenetic protein and/or inhibitors of activin/nodal signaling to obtain cells that express trophoblast markers. Trophoblasts can terminally differentiate to either extravillous trophoblasts or syncytiotrophoblasts. The signaling pathways that govern the terminal fate of these trophoblasts are not understood. We show that activin/nodal signaling switches the terminal fate of these hESC-derived trophoblasts. Inhibition of activin/nodal signaling leads to formation of extravillous trophoblast, whereas loss of activin/nodal inhibition leads to the formation of syncytiotrophoblasts. Also, the ability of hESCs to form bona fide trophoblasts has been intensely debated. We have examined hESC-derived trophoblasts in the light of stringent criteria that were proposed recently, such as hypomethylation of the ELF5-2b promoter region and down-regulation of HLA class I antigens. We report that trophoblasts that possess these properties can indeed be obtained from hESCs. Human embryonic stem cells (hESCs) have been routinely treated with bone morphogenetic protein and/or inhibitors of activin/nodal signaling to obtain cells that express trophoblast markers. Trophoblasts can terminally differentiate to either extravillous trophoblasts or syncytiotrophoblasts. The signaling pathways that govern the terminal fate of these trophoblasts are not understood. We show that activin/nodal signaling switches the terminal fate of these hESC-derived trophoblasts. Inhibition of activin/nodal signaling leads to formation of extravillous trophoblast, whereas loss of activin/nodal inhibition leads to the formation of syncytiotrophoblasts. Also, the ability of hESCs to form bona fide trophoblasts has been intensely debated. We have examined hESC-derived trophoblasts in the light of stringent criteria that were proposed recently, such as hypomethylation of the ELF5-2b promoter region and down-regulation of HLA class I antigens. We report that trophoblasts that possess these properties can indeed be obtained from hESCs. DA - 2015/4/3/ PY - 2015/4/3/ DO - 10.1074/jbc.m114.620641 VL - 290 IS - 14 SP - 8834-8848 SN - 1083-351X ER - TY - JOUR TI - The importance of retaining a phylogenetic perspective in traits-based community analyses AU - Poteat, Monica D. AU - Jacobus, Luke M. AU - Buchwalter, David B. T2 - FRESHWATER BIOLOGY AB - Summary Many environmental stressors manifest their effects via physiological processes (traits) that can differ significantly among species and species groups. We compiled available data for three traits related to the bioconcentration of the toxic metal cadmium ( Cd ) from 42 species representing the aquatic insect orders E phemeroptera (mayflies), P lecoptera (stoneflies) and T richoptera (caddisflies). These traits included the propensity to take up Cd from water (uptake rate constant, k u ), the ability to excrete Cd (efflux rate constant, k e ) and the net result of these two processes (bioconcentration factor). Ranges in these Cd bioaccumulation traits varied in magnitude across clades (some clades had a greater tendency to bioaccumulate Cd than others). Overlap in the ranges of trait values among different clades was common and highlights situations where species from different lineages can share a similar trait state, but represent the high end of possible physiological values for one clade and the low end for another. Variance around the mean trait states differed widely across clades, suggesting that some groups (e.g. E phemerellidae) are inherently more variable than others (e.g. P erlidae). Thus, trait variability/lability is at least partially a function of lineage. Akaike information criterion comparisons of statistical models were more often driven by lineage than by the other tested potential biological or ecological explanations. Lineage‐driven models generally improved with increasing taxonomic resolution. Together, these findings suggest that lineage provides context for the analysis of species traits and that failure to consider lineage in community‐based analysis of traits may obscure important patterns of species responses to environmental change. DA - 2015/7// PY - 2015/7// DO - 10.1111/fwb.12571 VL - 60 IS - 7 SP - 1330-1339 SN - 1365-2427 KW - aquatic insects KW - metals KW - physiology KW - traits KW - variability ER - TY - JOUR TI - Machine learning reveals sex-specific 17β-estradiol-responsive expression patterns in white perch (Morone americana) plasma proteins AU - Schilling, Justin AU - Nepomuceno, Angelito I. AU - Planchart, Antonio AU - Yoder, Jeffrey A. AU - Kelly, Robert M. AU - Muddiman, David C. AU - Daniels, Harry V. AU - Hiramatsu, Naoshi AU - Reading, Benjamin J. T2 - PROTEOMICS AB - With growing abundance and awareness of endocrine disrupting compounds (EDCs) in the environment, there is a need for accurate and reliable detection of EDC exposure. Our objective in the present study was to observe differences within and between the global plasma proteomes of sexually mature male and female white perch ( Morone americana ) before (Initial Control, IC) and after 17β‐estradiol (E 2 ) induction. Semiquantitative nanoLC‐MS/MS data were analyzed by machine learning support vector machines (SVMs) and by two‐way ANOVA. By ANOVA, the expression levels of 44, 77, and 57 proteins varied significantly by gender, treatment, and the interaction of gender and treatment, respectively. SVMs perfectly classified male and female perch IC and E 2 ‐induced plasma samples using the protein expression data. E 2 ‐induced male and female perch plasma proteomes contained significantly higher levels of the yolk precursors vitellogenin Aa and Ab (VtgAa, VtgAb), as well as latrophilin and seven transmembrane domain‐containing protein 1 (Eltd1) and kininogen 1 (Kng1). This is the first report that Eltd1 and Kng1 may be E 2 ‐responsive proteins in fishes and therefore may be useful indicators of estrogen induction. DA - 2015/6/11/ PY - 2015/6/11/ DO - 10.1002/pmic.201400606 VL - 15 IS - 15 SP - 2678-2690 J2 - Proteomics LA - en OP - SN - 1615-9853 UR - http://dx.doi.org/10.1002/pmic.201400606 DB - Crossref KW - Animal proteomics KW - Endocrine disrupting compounds KW - Machine learning KW - Plasma KW - Semiquantitative proteomics KW - Support vector machines ER - TY - JOUR TI - Incidence of solid tumours among pesticide applicators exposed to the organophosphate insecticide diazinon in the Agricultural Health Study: an updated analysis AU - Jones, R. R. AU - Barone-Adesi, F. AU - Koutros, S. AU - Lerro, C. C. AU - Blair, A. AU - Lubin, J. AU - Heltshe, S. L. AU - Hoppin, Jane AU - Alavanja, M. C. R. AU - Freeman, L. E. B. AU - al. T2 - Occupational and Environmental Medicine AB -

Objective

Diazinon, a common organophosphate insecticide with genotoxic properties, was previously associated with lung cancer in the Agricultural Health Study (AHS) cohort, but few other epidemiological studies have examined diazinon-associated cancer risk. We used updated diazinon exposure and cancer incidence information to evaluate solid tumour risk in the AHS.

Methods

Male pesticide applicators in Iowa and North Carolina reported lifetime diazinon use at enrolment (1993–1997) and follow-up (1998–2005); cancer incidence was assessed through 2010(North Carolina)/2011(Iowa). Among applicators with usage information sufficient to evaluate exposure-response patterns, we used Poisson regression to estimate adjusted rate ratios (RRs) and 95% CI for cancer sites with ≥10 exposed cases for both lifetime (LT) exposure days and intensity-weighted (IW) lifetime exposure days (accounting for factors impacting exposure).

Results

We observed elevated lung cancer risks (N=283) among applicators with the greatest number of LT (RR=1.60; 95% CI 1.11 to 2.31; Ptrend=0.02) and IW days of diazinon use (RR=1.41; 95% CI 0.98 to 2.04; Ptrend=0.08). Kidney cancer (N=94) risks were non-significantly elevated (RRLT days=1.77; 95% CI 0.90 to 3.51; Ptrend=0.09; RRIW days 1.37; 95% CI 0.64 to 2.92; Ptrend=0.50), as were risks for aggressive prostate cancer (N=656).

Conclusions

Our updated evaluation of diazinon provides additional evidence of an association with lung cancer risk. Newly identified links to kidney cancer and associations with aggressive prostate cancer require further evaluation. DA - 2015/4/23/ PY - 2015/4/23/ DO - 10.1136/oemed-2014-102728 VL - 72 IS - 7 SP - 496-503 J2 - Occup Environ Med LA - en OP - SN - 1351-0711 1470-7926 UR - http://dx.doi.org/10.1136/oemed-2014-102728 DB - Crossref ER - TY - JOUR TI - IARC monographs: 40 years of evaluating carcinogenic hazards to humans T2 - Environmental Health Perspectives DA - 2015/// PY - 2015/// VL - 123 IS - 6 SP - 507-514 ER - TY - JOUR TI - Evaluation of Copper Oxide Oxidation for Quantification of Lignin in Municipal Solid Waste AU - De la Cruz, Florentino Banaag AU - Dittmar, Thorsten AU - Niggemann, Jutta AU - Osburn, Christopher L. AU - Barlaz, Morton A. T2 - Environmental Engineering Science AB - The ability to quantify lignin is an important tool for characterizing the extent of decomposition of municipal solid waste (MSW). Traditionally, acid insoluble Klason lignin (KL) has been used to measure lignin. However, synthetic organic materials such as plastics and rubber present in MSW interfere with the traditional KL method, resulting in artificially high measurements. Another method for lignin analysis is CuO oxidation, in which lignin is oxidatively hydrolyzed into phenolic monomers that are quantified by high-performance liquid chromatography or gas chromatography–mass spectrography. The objective of this study was to evaluate the applicability of CuO oxidation to measure the lignin content of MSW. The study demonstrated that analysis of lignin monomers can be simplified by skipping the ethyl acetate extraction step and that ball milling is not necessary to optimize CuO oxidation. Neither the MSW components (e.g., plastics and metals) nor extractives affected CuO oxidation. The ratio of cellulose (Cel) plus hemicellulose (H) to KL [(Cel+H)/KL] has traditionally been used as an indicator of the extent of MSW decomposition. The use of Cel plus H to the sum of CuO oxidation products of lignin (Λ8) [(Cel+H)/Λ8] exhibited a similar trend to the traditional metric. CuO analysis provided information on the presence of hardwood, softwood, and nonwoody material in buried MSW, but is not recommended as a substitute for KL analysis. DA - 2015/6// PY - 2015/6// DO - 10.1089/ees.2014.0402 VL - 32 IS - 6 SP - 486-496 J2 - Environmental Engineering Science LA - en OP - SN - 1092-8758 1557-9018 UR - http://dx.doi.org/10.1089/ees.2014.0402 DB - Crossref KW - municipal solid waste KW - CuO oxidation KW - lignin ER - TY - JOUR TI - Assessing drug and metabolite detection in liver tissue by UV-MALDI and IR-MALDESI mass spectrometry imaging coupled to FT-ICR MS AU - Barry, Jeremy A. AU - Groseclose, M. Reid AU - Robichaud, Guillaume AU - Castellino, Stephen AU - Muddiman, David C. T2 - INTERNATIONAL JOURNAL OF MASS SPECTROMETRY AB - Determining the distribution of a drug and its metabolites within tissue is a key facet of evaluating drug candidates. Drug distribution can have a significant implication in appraising drug efficacy and potential toxicity. The specificity and sensitivity of mass spectrometry imaging (MSI) make it a perfect complement to the analysis of drug distributions in tissue. The detection of lapatinib as well as several of its metabolites in liver tissue was determined by MSI using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) coupled to high resolving power Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers. IR-MALDESI required minimal sample preparation while maintaining high sensitivity. The effect of the electrospray solvent composition on IR-MALDESI MSI signal from tissue analysis was investigated and an empirical comparison of IR-MALDESI and UV-MALDI for MSI analysis is also presented. DA - 2015/2/1/ PY - 2015/2/1/ DO - 10.1016/j.ijms.2014.05.012 VL - 377 SP - 448-455 SN - 1873-2798 KW - MALDI KW - IR-MALDESI KW - Mass spectrometry imaging KW - Drug distribution ER - TY - JOUR TI - A Review of Nonoccupational Pathways for Pesticide Exposure in Women Living in Agricultural Areas AU - Deziel, Nicole C. AU - Friesen, Melissa C. AU - Hoppin, Jane A. AU - Hines, Cynthia J. AU - Thomas, Kent AU - Freeman, Laura E. Beane T2 - Environmental Health Perspectives AB - BackgroundWomen living in agricultural areas may experience high pesticide exposures compared with women in urban or suburban areas because of their proximity to farm activities.ObjectiveOur objective was to review the evidence in the published literature for the contribution of nonoccupational pathways of pesticide exposure in women living in North American agricultural areas.MethodsWe evaluated the following nonoccupational exposure pathways: paraoccupational (i.e., take-home or bystander exposure), agricultural drift, residential pesticide use, and dietary ingestion. We also evaluated the role of hygiene factors (e.g., house cleaning, shoe removal).ResultsAmong 35 publications identified (published 1995–2013), several reported significant or suggestive (p < 0.1) associations between paraoccupational (n = 19) and agricultural drift (n = 10) pathways and pesticide dust or biomarker levels, and 3 observed that residential use was associated with pesticide concentrations in dust. The 4 studies related to ingestion reported low detection rates of most pesticides in water; additional studies are needed to draw conclusions about the importance of this pathway. Hygiene factors were not consistently linked to exposure among the 18 relevant publications identified.ConclusionsEvidence supported the importance of paraoccupational, drift, and residential use pathways. Disentangling exposure pathways was difficult because agricultural populations are concurrently exposed to pesticides via multiple pathways. Most evidence was based on measurements of pesticides in residential dust, which are applicable to any household member and are not specific to women. An improved understanding of nonoccupational pesticide exposure pathways in women living in agricultural areas is critical for studying health effects in women and for designing effective exposure-reduction strategies.CitationDeziel NC, Friesen MC, Hoppin JA, Hines CJ, Thomas K, Beane Freeman LE. 2015. A review of nonoccupational pathways for pesticide exposure in women living in agricultural areas. Environ Health Perspect 123:515–524; http://dx.doi.org/10.1289/ehp.1408273 DA - 2015/6// PY - 2015/6// DO - 10.1289/ehp.1408273 VL - 123 IS - 6 SP - 515-524 J2 - Environmental Health Perspectives LA - en OP - SN - 0091-6765 1552-9924 UR - http://dx.doi.org/10.1289/ehp.1408273 DB - Crossref ER - TY - JOUR TI - Mass Spectrometry Imaging Reveals Heterogeneous Efavirenz Distribution within Putative HIV Reservoirs AU - Thompson, Corbin G. AU - Bokhart, Mark T. AU - Sykes, Craig AU - Adamson, Lourdes AU - Fedoriw, Yuri AU - Luciw, Paul A. AU - Muddiman, David C. AU - Kashuba, Angela D. M. AU - Rosen, Elias P. T2 - ANTIMICROBIAL AGENTS AND CHEMOTHERAPY AB - ABSTRACT Persistent HIV replication within active viral reservoirs may be caused by inadequate antiretroviral penetration. Here, we used mass spectrometry imaging with infrared matrix-assisted laser desorption–electrospray ionization to quantify the distribution of efavirenz within tissues from a macaque dosed orally to a steady state. Intratissue efavirenz distribution was heterogeneous, with the drug concentrating in the lamina propria of the colon, the primary follicles of lymph nodes, and the brain gray matter. These are the first imaging data of an antiretroviral drug in active viral reservoirs. DA - 2015/5// PY - 2015/5// DO - 10.1128/aac.04952-14 VL - 59 IS - 5 SP - 2944-2948 SN - 1098-6596 ER - TY - JOUR TI - Cellular-level mass spectrometry imaging using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) by oversampling AU - Nazari, Milad AU - Muddiman, David C. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY AB - Mass spectrometry imaging (MSI) allows for the direct and simultaneous analysis of the spatial distribution of molecular species from sample surfaces such as tissue sections. One of the goals of MSI is monitoring the distribution of compounds at the cellular resolution in order to gain insights about the biology that occurs at this spatial level. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) imaging of cervical tissue sections was performed using a spot-to-spot distance of 10 μm by utilizing the method of oversampling, where the target plate is moved by a distance that is less than the desorption radius of the laser. In addition to high spatial resolution, high mass accuracy (±1 ppm) and high mass resolving power (140,000 at m/z = 200) were achieved by coupling the IR-MALDESI imaging source to a hybrid quadrupole Orbitrap mass spectrometer. Ion maps of cholesterol in tissues were generated from voxels containing <1 cell, on average. Additionally, the challenges of imaging at the cellular level in terms of loss of sensitivity and longer analysis time are discussed. DA - 2015/3// PY - 2015/3// DO - 10.1007/s00216-014-8376-5 VL - 407 IS - 8 SP - 2265-2271 SN - 1618-2650 KW - Mass spectrometry imaging KW - Infrared KW - MALDESI KW - Cellular analysis KW - Oversampling KW - Tissue analysis KW - Lipids ER - TY - JOUR TI - Quantitative mass spectrometry imaging of emtricitabine in cervical tissue model using infrared matrix-assisted laser desorption electrospray ionization AU - Bokhart, Mark T. AU - Rosen, Elias AU - Thompson, Corbin AU - Sykes, Craig AU - Kashuba, Angela D. M. AU - Muddiman, David C. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY AB - A quantitative mass spectrometry imaging (QMSI) technique using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is demonstrated for the antiretroviral (ARV) drug emtricitabine in incubated human cervical tissue. Method development of the QMSI technique leads to a gain in sensitivity and removal of interferences for several ARV drugs. Analyte response was significantly improved by a detailed evaluation of several cationization agents. Increased sensitivity and removal of an isobaric interference was demonstrated with sodium chloride in the electrospray solvent. Voxel-to-voxel variability was improved for the MSI experiments by normalizing analyte abundance to a uniformly applied compound with similar characteristics to the drug of interest. Finally, emtricitabine was quantified in tissue with a calibration curve generated from the stable isotope-labeled analog of emtricitabine followed by cross-validation using liquid chromatography tandem mass spectrometry (LC-MS/MS). The quantitative IR-MALDESI analysis proved to be reproducible with an emtricitabine concentration of 17.2 ± 1.8 μg/gtissue. This amount corresponds to the detection of 7 fmol/voxel in the IR-MALDESI QMSI experiment. Adjacent tissue slices were analyzed using LC-MS/MS which resulted in an emtricitabine concentration of 28.4 ± 2.8 μg/gtissue. DA - 2015/3// PY - 2015/3// DO - 10.1007/s00216-014-8220-y VL - 407 IS - 8 SP - 2073-2084 SN - 1618-2650 KW - Mass spectrometry imaging KW - IR-MALDESI KW - Absolute quantification KW - Drug distribution KW - HIV KW - Selected reaction monitoring ER - TY - JOUR TI - Full- and pilot-scale GAC adsorption of organic micropollutants AU - Kennedy, Anthony M. AU - Reinert, Allison M. AU - Knappe, Detlef R. U. AU - Ferrer, Imma AU - Summers, R. Scott T2 - WATER RESEARCH AB - Granular activated carbon (GAC) adsorption of 30 environmentally relevant micropollutants (MP) from four surface waters was investigated at the pilot-scale with empty bed contact times (EBCTs) of 7 and 15 min. An increase in background dissolved organic matter resulted in more and earlier MP breakthrough. Compared to an EBCT of 7 min, MP breakthrough at an EBCT of 15 min demonstrated 52% later breakthrough on average for five MPs on a throughput basis. A regression model was developed with data from three waters to predict MP throughput in bed volumes to 10% breakthrough (BV10%) based on the influent dissolved organic carbon concentration and the MP pH-dependent octanol-water partition coefficient, polarizability, and molecular volume. The regression model over predicted full-scale BV10% values when applied to a wastewater-water impacted water source and to GAC with a larger particle diameter, for which a particle size adjustment was able to account for most of the difference. DA - 2015/1/1/ PY - 2015/1/1/ DO - 10.1016/j.watres.2014.10.010 VL - 68 SP - 238-248 SN - 0043-1354 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84908518266&partnerID=MN8TOARS KW - Granular activated carbon KW - Trace organic contaminants KW - Drinking water treatment KW - Pesticides KW - Pharmaceuticals KW - Personal care products ER - TY - JOUR TI - Analysis of trace fibers by IR-MALDESI imaging coupled with high resolving power MS AU - Cochran, Kristin H. AU - Barry, Jeremy A. AU - Robichaud, Guillaume AU - Muddiman, David C. T2 - ANALYTICAL AND BIOANALYTICAL CHEMISTRY AB - Trace evidence is a significant portion of forensic cases. Textile fibers are a common form of trace evidence that are gaining importance in criminal cases. Currently, qualitative techniques that do not yield structural information are primarily used for fiber analysis, but mass spectrometry is gaining an increasing role in this field. Mass spectrometry yields more quantitative structural information about the dye and polymer that can be used for more conclusive comparisons. Matrix-assisted laser desorption electrospray ionization (MALDESI) is a hybrid ambient ionization source being investigated for use in mass spectrometric fiber analysis. In this manuscript, IR-MALDESI was used as a source for mass spectrometry imaging (MSI) of a dyed nylon fiber cluster and single fiber. Information about the fiber polymer as well as the dye were obtained from a single fiber which was on the order of 10 μm in diameter. These experiments were performed directly from the surface of a tape lift of the fiber with a background of extraneous fibers. DA - 2015/1// PY - 2015/1// DO - 10.1007/s00216-014-8042-y VL - 407 IS - 3 SP - 813-820 SN - 1618-2650 KW - Mass spectrometry imaging KW - Forensic science KW - Trace evidence KW - Polarity switching imaging KW - MALDESI ER - TY - JOUR TI - The Comparative Toxicogenomics Database's 10th year anniversary: update 2015 AU - Davis, Allan Peter AU - Grondin, Cynthia J. AU - Lennon-Hopkins, Kelley AU - Saraceni-Richards, Cynthia AU - Sciaky, Daniela AU - King, Benjamin L. AU - Wiegers, Thomas C. AU - Mattingly, Carolyn J. T2 - NUCLEIC ACIDS RESEARCH AB - Ten years ago, the Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) was developed out of a need to formalize, harmonize and centralize the information on numerous genes and proteins responding to environmental toxic agents across diverse species. CTD's initial approach was to facilitate comparisons of nucleotide and protein sequences of toxicologically significant genes by curating these sequences and electronically annotating them with chemical terms from their associated references. Since then, however, CTD has vastly expanded its scope to robustly represent a triad of chemical-gene, chemical-disease and gene-disease interactions that are manually curated from the scientific literature by professional biocurators using controlled vocabularies, ontologies and structured notation. Today, CTD includes 24 million toxicogenomic connections relating chemicals/drugs, genes/proteins, diseases, taxa, phenotypes, Gene Ontology annotations, pathways and interaction modules. In this 10th year anniversary update, we outline the evolution of CTD, including our increased data content, new 'Pathway View' visualization tool, enhanced curation practices, pilot chemical-phenotype results and impending exposure data set. The prototype database originally described in our first report has transformed into a sophisticated resource used actively today to help scientists develop and test hypotheses about the etiologies of environmentally influenced diseases. DA - 2015/1/28/ PY - 2015/1/28/ DO - 10.1093/nar/gku935 VL - 43 IS - D1 SP - D914-D920 SN - 1362-4962 ER - TY - PCOMM TI - Michael Gross: 25 Years of Dedication and Leadership of JASMS (1990-2015) AU - Muddiman, David C. DA - 2015/1// PY - 2015/1// DO - 10.1007/s13361-014-1040-7 SP - 1-4 ER - TY - JOUR TI - 4-Coumaroyl and Caffeoyl Shikimic Acids Inhibit 4-Coumaric Acid: Coenzyme A Ligases and Modulate Metabolic Flux for 3-Hydroxylation in Monolignol Biosynthesis of Populus trichocarpa AU - Lin, Chien-Yuan AU - Wang, Jack P. AU - Li, Quanzi AU - Chen, Hsi-Chuan AU - Liu, Jie AU - Loziuk, Philip AU - Song, Jina AU - Williams, Cranos AU - Muddiman, David C. AU - Sederoff, Ronald R. AU - Chiang, Vincent L. T2 - MOLECULAR PLANT AB - Downregulation of 4-coumaric acid:coenzyme A ligase (4CL) can reduce lignin content in a number of plant species. In lignin precursor (monolignol) biosynthesis during stem wood formation in Populus trichocarpa, two enzymes, Ptr4CL3 and Ptr4CL5, catalyze the coenzyme A (CoA) ligation of 4-coumaric acid to 4-coumaroyl-CoA and caffeic acid to caffeoyl-CoA. CoA ligation of 4-coumaric acid is essential for the 3-hydroxylation of 4-coumaroyl shikimic acid. This hydroxylation results from sequential reactions of 4-hydroxycinnamoyl-CoA:shikimic acid hydroxycinnamoyl transferases (PtrHCT1 and PtrHCT6) and 4-coumaric acid 3-hydroxylase 3 (PtrC3H3). Alternatively, 3-hydroxylation of 4-coumaric acid to caffeic acid may occur through an enzyme complex of cinnamic acid 4-hydroxylase 1 and 2 (PtrC4H1 and PtrC4H2) and PtrC3H3. We found that 4-coumaroyl and caffeoyl shikimic acids are inhibitors of Ptr4CL3 and Ptr4CL5. 4-Coumaroyl shikimic acid strongly inhibits the formation of 4-coumaroyl-CoA and caffeoyl-CoA. Caffeoyl shikimic acid inhibits only the formation of 4-coumaroyl-CoA. 4-Coumaroyl and caffeoyl shikimic acids both act as competitive and uncompetitive inhibitors. Metabolic flux in wild-type and PtrC3H3 downregulated P. trichocarpa transgenics has been estimated by absolute protein and metabolite quantification based on liquid chromatography–tandem mass spectrometry, mass action kinetics, and inhibition equations. Inhibition by 4-coumaroyl and caffeoyl shikimic acids may play significant regulatory roles when these inhibitors accumulate. DA - 2015/1/5/ PY - 2015/1/5/ DO - 10.1016/j.molp.2014.12.003 VL - 8 IS - 1 SP - 176-187 SN - 1752-9867 KW - monolignol biosynthesis KW - Populus trichocarpa KW - metabolic flux KW - reaction and inhibition kinetics KW - LC-MS/MS KW - 4-coumaroyl and caffeoyl shikimic acids ER - TY - JOUR TI - Understanding the low-frequency variability in hydroclimatic attributes over the southeastern US AU - Wang, Hui AU - Sankarasubramanian, A. AU - Ranjithan, R. S. T2 - JOURNAL OF HYDROLOGY AB - Most studies on evaluating the potential in developing seasonal to interannual hydroclimatic forecasts have focused on associating low-frequency climatic conditions with basin-level precipitation/streamflow. The motivation of this study is to provide an understanding on how land surface characteristics modulate the low-frequency (interannual to decadal) variability in precipitation to develop low-frequency signal in streamflow. For this purpose, we consider basins with minimum anthropogenic impacts over southeastern United States and apply Singular Spectrum Analysis (SSA), a data-driven spectrum analysis tool, on annual precipitation and streamflow time series for detecting the dominant frequencies and for estimating the associated variability with them. Hypothesis test against an AR(1) process is carried out via Monte Carlo SSA for detecting significant (at 90% confidence level) low-frequency oscillations. Thus, the study investigates how the observed low-frequency oscillations in precipitation/streamflow vary over the southeastern United States and also their associations with climatic conditions. For most study basins, precipitation exhibits higher low-frequency oscillations than that of streamflow primarily due to reduction in variability by basin storage. Investigating this further, we found that the percentage variance accounted by low-frequency oscillations in streamflow being higher for larger basins which primarily indicates the increased role of climate and basin storage. To develop a fundamental understanding on how basin storage controls the low-frequency oscillations in streamflow, a simple annual hydrological model is employed to explore how the given low-frequency signal in precipitation being modified under different baseflow index conditions and groundwater residence time. Implications of these analyses relating to streamflow predictions and model calibration are also discussed. DA - 2015/2// PY - 2015/2// DO - 10.1016/j.jhydrol.2014.09.081 VL - 521 SP - 170-181 SN - 1879-2707 KW - Interannual variability KW - Decadal oscillations KW - Singular Spectrum Analysis KW - Basin storage effect KW - Water management ER - TY - JOUR TI - SOURCES OF ENDOCRINE-DISRUPTING COMPOUNDS IN NORTH CAROLINA WATERWAYS: A GEOGRAPHIC INFORMATION SYSTEMS APPROACH AU - Sackett, Dana K. AU - Pow, Crystal Lee AU - Rubino, Matthew J. AU - Aday, D. Derek AU - Cope, W. Gregory AU - Kullman, Seth AU - Rice, James A. AU - Kwak, Thomas J. AU - Law, Mac T2 - ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY AB - The presence of endocrine-disrupting compounds (EDCs), particularly estrogenic compounds, in the environment has drawn public attention across the globe, yet a clear understanding of the extent and distribution of estrogenic EDCs in surface waters and their relationship to potential sources is lacking. The objective of the present study was to identify and examine the potential input of estrogenic EDC sources in North Carolina water bodies using a geographic information system (GIS) mapping and analysis approach. Existing data from state and federal agencies were used to create point and nonpoint source maps depicting the cumulative contribution of potential sources of estrogenic EDCs to North Carolina surface waters. Water was collected from 33 sites (12 associated with potential point sources, 12 associated with potential nonpoint sources, and 9 reference), to validate the predictive results of the GIS analysis. Estrogenicity (measured as 17β-estradiol equivalence) ranged from 0.06 ng/L to 56.9 ng/L. However, the majority of sites (88%) had water 17β-estradiol concentrations below 1 ng/L. Sites associated with point and nonpoint sources had significantly higher 17β-estradiol levels than reference sites. The results suggested that water 17β-estradiol was reflective of GIS predictions, confirming the relevance of landscape-level influences on water quality and validating the GIS approach to characterize such relationships. DA - 2015/2// PY - 2015/2// DO - 10.1002/etc.2797 VL - 34 IS - 2 SP - 437-445 SN - 1552-8618 KW - Ecotoxicology KW - Endocrine disrupting compound KW - Estrogenicity KW - Geographic information system prediction KW - Surface water ER - TY - JOUR TI - Protective glove use and hygiene habits modify the associations of specific pesticides with Parkinson's disease AU - Furlong, Melissa AU - Tanner, Caroline M. AU - Goldman, Samuel M. AU - Bhudhikanok, Grace S. AU - Blair, Aaron AU - Chade, Anabel AU - Comyns, Kathleen AU - Hoppin, Jane A. AU - Kasten, Meike AU - Korell, Monica AU - Langston, J. William AU - Marras, Connie AU - Meng, Cheryl AU - Richards, Marie AU - Ross, G. Webster AU - Umbach, David M. AU - Sandler, Dale P. AU - Kamel, Freya T2 - Environment International AB - Pesticides have been associated with Parkinson's disease (PD), and protective gloves and workplace hygiene can reduce pesticide exposure. We assessed whether use of gloves and workplace hygiene modified associations between pesticides and PD. The Farming and Movement Evaluation (FAME) study is a nested case-control study within the Agricultural Health Study. Use of protective gloves, other PPE, and hygiene practices were determined by questionnaire (69 cases and 237 controls were included). We considered interactions of gloves and hygiene with ever-use of pesticides for all pesticides with ≥5 exposed and unexposed cases and controls in each glove-use stratum (paraquat, permethrin, rotenone, and trifluralin). 61% of respondents consistently used protective gloves and 87% consistently used ≥2 hygiene practices. Protective glove use modified the associations of paraquat and permethrin with PD: neither pesticide was associated with PD among protective glove users, while both pesticides were associated with PD among non-users (paraquat OR 3.9 [95% CI 1.3, 11.7], interaction p=0.15; permethrin OR 4.3 [95% CI 1.2, 15.6] interaction p=0.05). Rotenone was associated with PD regardless of glove use. Trifluralin was associated with PD among participants who used <2 hygiene practices (OR 5.5 [95% CI 1.1, 27.1]) but was not associated with PD among participants who used 2 or more practices (interaction p=0.02). Although sample size was limited in the FAME study, protective glove use and hygiene practices appeared to be important modifiers of the association between pesticides and PD and may reduce risk of PD associated with certain pesticides. DA - 2015/2// PY - 2015/2// DO - 10.1016/j.envint.2014.11.002 VL - 75 SP - 144-150 J2 - Environment International LA - en OP - SN - 0160-4120 UR - http://dx.doi.org/10.1016/j.envint.2014.11.002 DB - Crossref KW - Personal protective equipment KW - Parkinson's disease KW - Pesticides KW - Neurodegenerative diseases KW - Movement disorders ER - TY - JOUR TI - Neutralization of Mitochondrial Superoxide by Superoxide Dismutase 2 Promotes Bacterial Clearance and Regulates Phagocyte Numbers in Zebrafish AU - Peterman, E. M. AU - Sullivan, C. AU - Goody, M. F. AU - Rodriguez-Nunez, I. AU - Yoder, J. A. AU - Kim, C. H. T2 - INFECTION AND IMMUNITY AB - Mitochondria are known primarily as the location of the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as by-products of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Because of the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multiorgan failure or death. Pseudomonas aeruginosa is an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated with P. aeruginosa are capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response to P. aeruginosa infection. sod2 is upregulated in mammalian macrophages and neutrophils in response to lipopolysaccharide in vitro, and sod2 knockdown in zebrafish results in an increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrion-targeted ROS scavengers as potential adjuvant therapies during severe infections. DA - 2015/1// PY - 2015/1// DO - 10.1128/iai.02245-14 VL - 83 IS - 1 SP - 430-440 SN - 1098-5522 ER - TY - JOUR TI - Investing in prospective cohorts for etiologic study of occupational exposures AU - Blair, A. AU - Hines, C.J. AU - Thomas, K.W. AU - Alavanja, M.C.R. AU - Freeman, L.E. Beane AU - Hoppin, J.A. AU - Kamel, F. AU - Lynch, C.F. AU - Lubin, J.H. AU - Silverman, D.T. AU - Whelan, E. AU - Zahm, S. H. AU - Sandler, D. P. T2 - American Journal of Industrial Medicine AB - Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures. Am. J. Ind. Med. 58:113–122, 2015. © 2015 Wiley Periodicals, Inc. DA - 2015/1/20/ PY - 2015/1/20/ DO - 10.1002/ajim.22403 VL - 58 IS - 2 SP - 113-122 J2 - Am. J. Ind. Med. LA - en OP - SN - 0271-3586 UR - http://dx.doi.org/10.1002/ajim.22403 DB - Crossref KW - prospective cohorts KW - agricultural exposures KW - occupational epidemiology ER - TY - JOUR TI - Farm Characteristics, Allergy Symptoms, and Risk of Non-Hodgkin Lymphoid Neoplasms in the Agricultural Health Study AU - Hofmann, J. N. AU - Hoppin, J. A. AU - Lynch, C. F. AU - Poole, J. A. AU - Purdue, M. P. AU - Blair, A. AU - Alavanja, M. C. AU - Beane Freeman, L. E. T2 - Cancer Epidemiology Biomarkers & Prevention AB - Abstract Background: Because of unique exposures, studies among farmers may yield insights into the relationship between allergies and non-Hodgkin lymphoid (NHL) neoplasms. We evaluated farm characteristics, allergic symptoms and conditions, and risk of NHL including specific subtypes in the Agricultural Health Study, a prospective cohort of farmers and spouses from North Carolina and Iowa. Methods: We identified 710 incident cases of NHL (including chronic lymphocytic leukemia and multiple myeloma) among 82,370 participants with baseline data on crop and animal exposures, including 454 cases among 52,850 participants with baseline data on recent allergy symptoms (rhinitis) and living on a farm during childhood. HR and 95% confidence intervals (CI) were calculated using multivariable-adjusted proportional hazards models. Results: We observed reduced risks of NHL among farmers and spouses with rhinitis at baseline (HR, 0.63; 95% CI, 0.51–0.79), related to growing soybeans (HR, 0.80; 95% CI, 0.67–0.96), and among farmers who handled stored grains or hay (HR, 0.66; 95% CI, 0.52–0.82). Growing up on a farm was associated with increased NHL risk (HR, 1.51; 95% CI, 1.15–1.98). Results did not differ significantly by NHL subtype. Conclusions: Both the reduced risk of NHL among those with allergy symptoms and specific farm exposures in adulthood, and the increased risk among those who grew up on a farm suggest that the host immune response to agricultural allergens may influence NHL development. Impact: This prospective study is, to our knowledge, the first to investigate the relationship between allergy symptoms and NHL risk in farmers; confirmation of these findings in other farming populations is warranted. Cancer Epidemiol Biomarkers Prev; 24(3); 587–94. ©2015 AACR. DA - 2015/1/12/ PY - 2015/1/12/ DO - 10.1158/1055-9965.epi-14-1246 VL - 24 IS - 3 SP - 587-594 J2 - Cancer Epidemiology Biomarkers & Prevention LA - en OP - SN - 1055-9965 1538-7755 UR - http://dx.doi.org/10.1158/1055-9965.EPI-14-1246 DB - Crossref ER - TY - JOUR TI - Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma AU - Igartua, C. AU - Myers, R. A. AU - Mathias, R. A. AU - Pino-Yanes, M. AU - Eng, C. AU - Graves, P. E. AU - Levin, A. M. AU - Del-Rio-Navarro, B. E. AU - Jackson, D. J. AU - Livne, O. E. AU - Rafaels, N. AU - Edlund, C. K. AU - Yang, J. J. AU - Huntsman, S. AU - Salam, M. T. AU - Romieu, I. AU - Mourad, R. AU - al, et a T2 - Nature Communications DA - 2015/// PY - 2015/// VL - 6 ER - TY - JOUR TI - Characterization of Uncertainty in Estimation of Methane Collection from Select US Landfills AU - Wang, Xiaoming AU - Nagpure, Ajay S. AU - DeCarolis, Joseph F. AU - Barlaz, Morton A. T2 - ENVIRONMENTAL SCIENCE & TECHNOLOGY AB - Methane is a potent greenhouse gas generated from the anaerobic decomposition of waste in landfills. If captured, methane can be beneficially used to generate electricity. To inventory emissions and assist the landfill industry with energy recovery projects, the U.S. EPA developed the Landfill Gas Emissions Model (LandGEM) that includes two key parameters: the first-order decay rate (k) and methane production potential (L0). By using data from 11 U.S. landfills, Monte Carlo simulations were performed to quantify the effect of uncertainty in gas collection efficiency and municipal solid waste fraction on optimal k values and collectable methane. A dual-phase model and associated parameters were also developed to evaluate its performance relative to a single-phase model (SPM) similar to LandGEM. The SPM is shown to give lower error in estimating methane collection, with site-specific best-fit k values. Most of the optimal k values are notably greater than the U.S. EPA's default of 0.04 yr(-1), which implies that the gas generation decreases more rapidly than predicted at the current default. We translated the uncertainty in collectable methane into uncertainty in engine requirements and potential economic losses to demonstrate the practical significance to landfill operators. The results indicate that landfill operators could overpay for engine capacity by $30,000-780,000 based on overestimates of collectable methane. DA - 2015/2/3/ PY - 2015/2/3/ DO - 10.1021/es505268x VL - 49 IS - 3 SP - 1545-1551 SN - 1520-5851 ER - TY - JOUR TI - Analysis of material recovery facilities for use in life-cycle assessment AU - Pressley, Phillip N. AU - Levis, James W. AU - Damgaard, Anders AU - Barlaz, Morton A. AU - DeCarolis, Joseph F. T2 - WASTE MANAGEMENT AB - Insights derived from life-cycle assessment of solid waste management strategies depend critically on assumptions, data, and modeling at the unit process level. Based on new primary data, a process model was developed to estimate the cost and energy use associated with material recovery facilities (MRFs), which are responsible for sorting recyclables into saleable streams and as such represent a key piece of recycling infrastructure. The model includes four modules, each with a different process flow, for separation of single-stream, dual-stream, pre-sorted recyclables, and mixed-waste. Each MRF type has a distinct combination of equipment and default input waste composition. Model results for total amortized costs from each MRF type ranged from $19.8 to $24.9 per Mg (1Mg=1 metric ton) of waste input. Electricity use ranged from 4.7 to 7.8kWh per Mg of waste input. In a single-stream MRF, equipment required for glass separation consumes 28% of total facility electricity consumption, while all other pieces of material recovery equipment consume less than 10% of total electricity. The dual-stream and mixed-waste MRFs have similar electricity consumption to a single-stream MRF. Glass separation contributes a much larger fraction of electricity consumption in a pre-sorted MRF, due to lower overall facility electricity consumption. Parametric analysis revealed that reducing separation efficiency for each piece of equipment by 25% altered total facility electricity consumption by less than 4% in each case. When model results were compared with actual data for an existing single-stream MRF, the model estimated the facility's electricity consumption within 2%. The results from this study can be integrated into LCAs of solid waste management with system boundaries that extend from the curb through final disposal. DA - 2015/1// PY - 2015/1// DO - 10.1016/j.wasman.2014.09.012 VL - 35 SP - 307-317 SN - 0956-053X KW - Recycling KW - Material recovery facility KW - Life-cycle assessment KW - Municipal solid waste ER - TY - JOUR TI - Measurement of chemical leaching potential of sulfate from landfill disposed sulfate containing wastes AU - Sun, Wenjie AU - Barlaz, Morton A. T2 - WASTE MANAGEMENT AB - A number of sulfate-containing wastes are disposed in municipal solid wastes (MSW) landfills including residues from coal, wood, and MSW combustion, and construction and demolition (C&D) waste. Under anaerobic conditions that dominate landfills, the sulfate can be reduced to hydrogen sulfide which is problematic for several reasons including its low odor threshold, toxicity, and corrosive nature. The overall objective of this study was to evaluate existing protocols for the quantification of total leachable sulfate from solid samples and to compare their effectiveness and efficiency with a new protocol described in this study. Methods compared include two existing acid extraction protocols commonly used in the U.S., a pH neutral protocol that requires multiple changes of the leaching solution, and a new acid extraction method. The new acid extraction method was shown to be simple and effective to measure the leaching potential of sulfate from a range of landfill disposed sulfate-containing wastes. However, the acid extraction methods do not distinguish between sulfate and other forms of sulfur and are thus most useful when sulfate is the only form of sulfur present. DA - 2015/2// PY - 2015/2// DO - 10.1016/j.wasman.2014.11.014 VL - 36 SP - 191-196 SN - 0956-053X KW - Hydrogen sulfide KW - Sulfate-containing wastes KW - Municipal solid waste KW - Landfill ER -