46 results on '"Kupsco A"'
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2. Environmental Chemical Exposures and Mitochondrial Dysfunction: a Review of Recent Literature
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Aalekhya Reddam, Sarah McLarnan, and Allison Kupsco
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Health Status ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,Humans ,Environmental Exposure ,Management, Monitoring, Policy and Law ,Mitochondria ,Nature and Landscape Conservation - Abstract
Purpose of Review Mitochondria play various roles that are important for cell function and survival; therefore, significant mitochondrial dysfunction may have chronic consequences that extend beyond the cell. Mitochondria are already susceptible to damage, which may be exacerbated by environmental exposures. Therefore, the aim of this review is to summarize the recent literature (2012–2022) looking at the effects of six ubiquitous classes of compounds on mitochondrial dysfunction in human populations. Recent Findings The literature suggests that there are a number of biomarkers that are commonly used to identify mitochondrial dysfunction, each with certain advantages and limitations. Classes of environmental toxicants such as polycyclic aromatic hydrocarbons, air pollutants, heavy metals, endocrine-disrupting compounds, pesticides, and nanomaterials can damage the mitochondria in varied ways, with changes in mtDNA copy number and measures of oxidative damage the most commonly measured in human populations. Other significant biomarkers include changes in mitochondrial membrane potential, calcium levels, and ATP levels. Summary This review identifies the biomarkers that are commonly used to characterize mitochondrial dysfunction but suggests that emerging mitochondrial biomarkers, such as cell-free mitochondria and blood cardiolipin levels, may provide greater insight into the impacts of exposures on mitochondrial function. This review identifies that the mtDNA copy number and measures of oxidative damage are commonly used to characterize mitochondrial dysfunction, but suggests using novel approaches in addition to well-characterized ones to create standardized protocols. We identified a dearth of studies on mitochondrial dysfunction in human populations exposed to metals, endocrine-disrupting chemicals, pesticides, and nanoparticles as a gap in knowledge that needs attention.
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- 2022
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3. Epigenome-wide DNA methylation assists early intervention of Coronary Heart Disease with machine learning models
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Yike Shen, Feng Gao, Arce Domingo-Relloso, Allison Kupsco, Marianthi-Anna Kioumourtzoglou, Karin Haack, Maria Tellez-Plaza, Jason G. Umans, Amanda M. Fretts, Ying Zhang, Shelley A. Cole, Haotian Wu, Andrea A. Baccarelli, and Ana Navas-Acien
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General Earth and Planetary Sciences ,General Environmental Science - Published
- 2022
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4. Exposure to Ambient Air Pollution is Associated with Expression of Breastmilk miRNAs
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Elizabeth Holzhausen, William Patterson, Andrea Baccarelli, Allison Kupsco, Fred Lurmann, Michael Goran, and Tanya Alderete
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General Earth and Planetary Sciences ,General Environmental Science - Published
- 2022
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5. Mitochondrial DNA Copy Number Dynamics from Birth through Adolescence in a Population of Dominican and African American Children
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Allison Kupsco, Tessa Bloomquist, Heng Hu, Deliang Tang, Jeff Goldsmith, Andrew G Rundle, Julie B Herbstman, and Andrea A Baccarelli
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General Earth and Planetary Sciences ,General Environmental Science - Published
- 2022
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6. Air pollution and bone mineral density among Women’s Health Initiative participants: A mixture analysis
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Diddier Prada, Carolyn J. Crandall, Yike Shen, Allison Kupsco, Duanping Liao, James D. Stewart, Jeff D. Yanosky, Jean Wactawski-Wende, Nicole C. Wright, Nelson B. Watts, Longjian Liu, Aladdin H. Shadyab, Andrea Baccarelli, and Eric Whitsel
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General Earth and Planetary Sciences ,General Environmental Science - Published
- 2022
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7. Prenatal exposure to polybrominated diphenyl ethers and BMI Z-scores from 5 to 14 years
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Allison, Kupsco, Andreas, Sjödin, Whitney, Cowell, Richard, Jones, Sharon, Oberfield, Shuang, Wang, Lori A, Hoepner, Dympna, Gallagher, Andrea A, Baccarelli, Jeff, Goldsmith, Andrew G, Rundle, and Julie B, Herbstman
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Cohort Studies ,Maternal Exposure ,Pregnancy ,Child, Preschool ,Prenatal Exposure Delayed Effects ,Health, Toxicology and Mutagenesis ,Halogenated Diphenyl Ethers ,Public Health, Environmental and Occupational Health ,Humans ,Female ,Child ,Body Mass Index ,Flame Retardants - Abstract
Background Polybrominated diphenyl ethers (PBDEs) are flame-retardant compounds widely used in household products until phase out in 2004. PBDEs are endocrine disruptors and are suggested to influence signaling related to weight control. Prenatal exposures to PBDEs may alter childhood adiposity, yet few studies have examined these associations in human populations. Methods Data were collected from a birth cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners BDE-47, − 99, − 100, and − 153 were measured in cord plasma (ng/μL) and dichotomized into low (< 80th percentile) and high (>80th percentile) exposure categories. Height and weight were collected at ages 5, 7, 9, 11, and an ancillary visit from 8 to 14 years (n = 289). Mixed-effects models with random intercepts for participant were used to assess associations between concentrations of individual PBDE congeners or the PBDE sum and child BMI z-scores (BMIz). To assess associations between PBDEs and the change in BMIz over time, models including interactions between PBDE categories and child age and (child age)2 were fit. Quantile g-computation was used to investigate associations between BMIz and the total PBDE mixture. Models were adjusted for baseline maternal covariates: ethnicity, age, education, parity, partnership status, and receipt of public assistance, and child covariates: child sex and cord cholesterol and triglycerides. Results The prevalence of children with obesity at age 5 was 24.2% and increased to 30% at age 11. Neither cord levels of individual PBDEs nor the total PBDE mixture were associated with overall BMIz in childhood. The changes in BMIz across childhood were not different between children with low or high PBDEs. Results were similar when adjusting for postnatal PBDE exposures. Conclusions Prenatal PBDE exposures were not associated with child growth trajectories in a cohort of Dominican and African American children.
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- 2022
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8. Maternal haemoglobin levels in pregnancy and child DNA methylation: a study in the pregnancy and childhood epigenetics consortium
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Mariona Bustamante, Sebastian Rauschert, Anette-G. Ziegler, Isabella Annesi-Maesano, Guadalupe Estrada Gutierrez, Nour Baïz, Marjo-Riitta Järvelin, Debbie A Lawlor, Marja Vääräsmäki, Justiina Ronkainen, Sandra Hummel, Giancarlo Pesce, Marta Vives-Usano, Elisabeth B. Binder, Doretta Caramaschi, Tuomas Kvist, Estelle Lowry, Phillip E. Melton, Allan C. Just, Eero Kajantie, Sylvain Sebert, Munawar Hussain Soomro, Nadine Hummel, Sanna Mustaniemi, Elina Keikkala, Janine F. Felix, Anni Heiskala, Florianne O.L. Vehmeijer, Allison Kupsco, Rae-Chi Huang, Jonathan A Heiss, Mònica Guxens, Darina Czamara, Katri Räikkönen, Martine Vrijheid, Stephanie J. London, Jari Lahti, Pediatrics, Child and Adolescent Psychiatry / Psychology, Department of Psychology and Logopedics, Developmental Psychology Research Group, University of Helsinki, HUS Children and Adolescents, Lastentautien yksikkö, Clinicum, Children's Hospital, and Faculty of Medicine
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Epigenomics ,0301 basic medicine ,Cancer Research ,Physiology ,HYPOXIA ,Haemoglobin levels ,0601 Biochemistry and Cell Biology ,Epigenesis, Genetic ,Epigenome ,Hemoglobins ,0302 clinical medicine ,DESIGN ,3123 Gynaecology and paediatrics ,Pregnancy ,Child ,health care economics and organizations ,Genetics & Heredity ,DNA methylation ,ASSOCIATION ,Methylation ,Fetal Blood ,3. Good health ,1101 Medical Biochemistry and Metabolomics ,Child, Preschool ,030220 oncology & carcinogenesis ,Cord blood ,Female ,pregnancy ,Life Sciences & Biomedicine ,Research Article ,Research Paper ,Biochemistry & Molecular Biology ,Adolescent ,BIRTH ,Dna Methylation ,Maternal Haemoglobin ,Developmental Programming ,Offspring ,education ,Biology ,Maternal haemoglobin ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,developmental programming ,medicine ,Humans ,Epigenetics ,Molecular Biology ,0604 Genetics ,Fetus ,Science & Technology ,Infant, Newborn ,medicine.disease ,030104 developmental biology ,DISCOVERY ,Developmental Biology - Abstract
Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels. Study-specific funding information can be found in the Supplementary Methods. JR, AH, EL, and SS were supported by the European Union’s Horizon 2020 research and innovation program [grant numbers 633595 (DynaHEALTH) and 733206 (LifeCycle)], Academy of Finland [grant number 285547 (EGEA)] and the Biocenter Oulu. ACJ was funded by the National Institute of Environmental Health Sciences [grant number R00ES023450]. AK was supported by the National Institute of Environmental Health Sciences [grant number R01ES021357]. DCa was funded by the UK Medical Research Council [grant number MC_UU_00011/7]. EKa received funding from the Horizon2020 grant for RECAP Research on Children and Adults Born Preterm [grant number 733280], Academy of Finland [grant number 315690], Foundation for Pediatric Research, Novo Nordisk Foundation, Signe and Ane Gyllenberg Foundation and Sigrid Jusélius Foundation. EKe received funding from the Finnish Medical Association. MG was supported by Miguel Servet fellowship from the Institute of Health Carlos III [grant numbers MS13/00054, CP18/00018]. MVä received funding from the Research Funds of Oulu University Hospital, Juho Vainio Foundation and Signe and Ane Gyllenberg Foundation. RCH was supported by the National Health and Medical Research Council Fellowship Grants [grant number 1053384]. SJL was supported by the intramural research program of the National Institutes of Health, National Institute of Environmental Health Sciences. SM received funding from the University of Oulu Graduate School. SR was supported by National Health and Medical Research Council EU [grant number 1142858] and the Department of Health, Western Australia FutureHealth fund in connection with the European Union’s Horizon 2020 [grant number 733206].
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- 2021
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9. 6 An Interdisciplinary Approach to Studying the Mitochondrial Toxicity of Prenatal PAH Exposure
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Sarah McLarnan, Allison Kupsco, Tessa Bloomquist, Kathryn DeSantis, Julie Herbstman, and Brandon Pearson
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General Medicine - Abstract
OBJECTIVES/GOALS: This study models a framework for integrating epidemiological and experimental approaches to investigate the effect of prenatal polycyclic aromatic hydrocarbon (PAH) exposure on mitochondrial function (mtDNAcn, superoxide production and membrane potential) as a potential mechanism of toxicity. METHODS/STUDY POPULATION: The epidemiological aim of this study characterizes mitochondrial outcomes in samples of umbilical cord tissue and blood from two Manhattan based birth cohorts. Prenatal PAH exposure is quantified using silicone wristbands worn for 48 hours during the third trimester of pregnancy. Experimentally, we are applying a PAH mixture designed to emulate the exposure profile of the human cohorts to mouse preimplantation embryos on various dosing schedules and quantifying the same mitochondrial outcomes. mtDNAcn is quantified using rtPCR while superoxide production and membrane potential are measured using fluorescence microscopy. The goal of this study design is to leverage the strengths of each approach to draw more robust conclusions than could be derived from either alone. RESULTS/ANTICIPATED RESULTS: Preliminary results of this study have found associations between higher levels of PAH exposure and increased mitochondrial superoxide production and hyperpolarization of the mitochondrial membrane potential in mouse preimplantation embryos. We anticipate these findings to persist across dosing schedules. We furthermore expect a decrease in mtDNAcn in association with higher PAH exposure in umbilical cord tissue samples and decreased mtDNAcn with exposure to the PAH mixture in mouse embryos. DISCUSSION/SIGNIFICANCE: Characterizing the effect of prenatal PAH exposure on the mitochondria is a critical step in understanding the mechanisms that underlie the toxicity of this exposure. By employing a similar exposure mixture and mitochondrial outcomes across epidemiological and experimental approaches, we offer a model of true interdisciplinary research design.
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- 2023
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10. Maternal DNA Methylation Signatures of Arsenic Exposure is Associated with Adult Offspring Insulin Resistance in the Strong Heart Study
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Christian K. Dye, Arce Domingo-Relloso, Allison Kupsco, Naomi E. Tinkelman, Miranda J. Spratlen, Anne K. Bozack, Maria Tellez-Plaza, Walter Goessler, Karin Haack, Jason G. Umans, Andrea A. Baccarelli, Shelley A. Cole, and Ana Navas-Acien
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General Environmental Science - Published
- 2022
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11. Additional file 1 of Prenatal exposure to polybrominated diphenyl ethers and BMI Z-scores from 5 to 14 years
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Kupsco, Allison, Sjödin, Andreas, Cowell, Whitney, Jones, Richard, Oberfield, Sharon, Wang, Shuang, Hoepner, Lori A., Gallagher, Dympna, Baccarelli, Andrea A., Goldsmith, Jeff, Rundle, Andrew G., and Herbstman, Julie B.
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Additional file 1: Supplemental Fig. S1. Mean cord PBDE Pearson’s correlations across 10 multiply imputed datasets. The gradient indicates the strength of the correlation. Supplemental Fig. S2. Predicted BMI Z-score growth trajectories from age 5-14 years for children with high (blue, >80th percentile) and low (red) PBDEs. Supplemental Table S1. Summary of follow-up information for the 289 individuals included in the present analysis and the full population of 541 individuals with a BMI measurement between ages 5 and 14. Supplemental Table S2. Sensitivity analyses for associations between cord plasma PBDE measures and overall child BMI Z-scores from age 5–14 years. Supplemental Table S3. Associations between continuous cord plasma PBDE measures and overall child BMI Z-scores from age 5–14 years. Supplemental Table S4. Sensitivity analyses for associations between cord plasma PBDE dichotomized at the 65th and 90th percentiles and overall child BMI Z-scores from age 5–14 years. Supplemental Table S5. Sensitivity analyses for associations between cord plasma PBDEs and trajectories of child BMI from 5 to 14 years. Supplemental Table S6. Sensitivity analyses for associations between cord plasma PBDEs dichotomized at the 65th and 90th percentiles and trajectories of child BMI z-score from 5 to 14 years. Supplemental Table S7. Sensitivity analyses for associations between cord plasma PBDEs and trajectories of child BMI z-score from 5 to 14 years.
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- 2022
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12. Air Pollution and Decreased Bone Mineral Density Among Women's Health Initiative Participants
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Diddier Prada, Carolyn J. Crandall, Allison Kupsco, Marianthi-Anna Kioumourtzoglou, James D. Stewart, Duanping Liao, Jeff D. Yanosky, Andrea Ramirez, Jean Wactawski-Wende, Yike Shen, Gary Miller, Iuliana Ionita-Laza, Eric A. Whitsel, and Andrea A. Baccarelli
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History ,Polymers and Plastics ,General Medicine ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
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13. Maternal Phthalates Exposure and Blood Pressure during and after Pregnancy in the PROGRESS Study
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Haotian Wu, Allison Kupsco, Allan Just, Antonia M. Calafat, Emily Oken, Joseph M. Braun, Alison P. Sanders, Adriana Mercado-Garcia, Alejandra Cantoral, Ivan Pantic, Martha M. Téllez-Rojo, Robert O. Wright, Andrea A. Baccarelli, and Andrea L. Deierlein
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Research ,Health, Toxicology and Mutagenesis ,Phthalic Acids ,Public Health, Environmental and Occupational Health ,Blood Pressure - Abstract
Background: Phthalate exposure is ubiquitous and may affect biological pathways related to regulators of blood pressure. Given the profound changes in vasculature during pregnancy, pregnant women may be particularly susceptible to the potential effects of phthalates on blood pressure. Objectives: We examined associations of phthalate exposure during pregnancy with maternal blood pressure trajectories from mid-pregnancy through 72 months postpartum. Methods: Women with singleton pregnancies delivering a live birth in Mexico City were enrolled during the second trimester (n=892). Spot urine samples from the second and third trimesters were analyzed for 15 phthalate metabolites. Blood pressure and covariate data were collected over nine visits through 72 months postpartum. We used linear, logistic, and linear mixed models; latent class growth models (LCGMs); and Bayesian kernel machine regression to estimate the relationship of urinary phthalate biomarkers with maternal blood pressure. Results: As a joint mixture, phthalate biomarker concentrations during pregnancy were associated with higher blood pressure rise during mid-to-late gestation. With respect to individual biomarkers, second trimester concentrations of monobenzyl phthalate (MBzP) and di(2-ethylhexyl) phthalate biomarkers (ΣDEHP) were associated with higher third trimester blood pressure. Two trajectory classes were identified by LCGM, characterized by increasing blood pressure through 72 months postpartum (“increase–increase”) or decreased blood pressure through 18 months postpartum with a gradual increase thereafter (“decrease–increase”). Increasing exposure to phthalate mixtures during pregnancy was associated with higher odds of being in the increase–increase class. Similar associations were observed for mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and dibutyl phthalate (ΣDBP) biomarkers. When specific time periods were examined, we observed specific temporal relationships were observed for ΣDEHP, MECPTP, MBzP, and ΣDBP. Discussion: In our cohort of pregnant women from Mexico City, exposure to phthalates and phthalate biomarkers was associated with higher blood pressure during late pregnancy, as well as with long-term changes in blood pressure trajectories. https://doi.org/10.1289/EHP8562
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- 2021
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14. Prenatal exposure to polybrominated diphenyl ethers and birth outcomes
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Aalekhya Reddam, Andreas Sjödin, Whitney Cowell, Richard Jones, Shuang Wang, Frederica Perera, Julie B. Herbstman, and Allison Kupsco
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Pregnancy ,Maternal Exposure ,Prenatal Exposure Delayed Effects ,Infant, Newborn ,Halogenated Diphenyl Ethers ,Humans ,Birth Weight ,Female ,Biochemistry ,Flame Retardants ,General Environmental Science - Abstract
Polybrominated diphenyl ethers (PBDEs) were used as flame retardants and from their end-use products they can be released to accumulate within indoor environments. This may result in exposures to pregnant women with potential adverse effects on the developing fetus. While studies have shown associations between prenatal PBDE exposure and poor birth outcomes, research has mainly focused on birth weight and gestational age and may miss important indicators of newborn size.The sample included a cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners (BDE-47, BDE-99, BDE-100, and BDE-153) were measured in cord serum at birth and dichotomized into low (80th percentile) and high (80th percentile) categories. Weight, length, head circumference, and gestational age were measured at birth and the ponderal index (birth weight/length x 100), size for gestational age, and population-based z-scores were calculated (n = 305). Separate regression analyses were conducted to estimate associations between PBDEs or PBDE sum (ng/g lipid) and birth outcomes. Quantile g-computation was performed to estimate the effect of total PBDE mixture. We also assessed effect modification by sex and ethnicity.Adjusting for relevant covariates, the high exposure category of BDE-153 was associated with lower birth weight z-score (-0.25, 95% CI: -0.5, 0.0) and longer gestation (0.43 weeks, 95% CI: 0.07, 0.79). The high exposure category of BDE-99 was associated with lower birth length z-score (-0.55, 95% CI: -0.98, -0.12). There was a negative association between the overall PBDE mixture and birth length z-score (-0.10, 95% CI: -0.21, 0.00) per 1 quintile increase in PBDEs. There was no effect modification by sex or ethnicity.These results suggest that prenatal exposures to BDE-153, BDE-99, and total PBDE mixture are associated with birth outcomes in a cohort of Dominican and African American newborns.
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- 2023
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15. Prenatal Maternal Phthalate Exposures and Trajectories of Childhood Adiposity from Four to Twelve Years
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Emily Oken, Robert O. Wright, Allan C. Just, Andrea A. Baccarelli, Antonia M. Calafat, Andrea Deierlein, Alejandra Cantoral, Joseph M. Braun, Martha María Téllez Rojo, and Allison Kupsco
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chemistry.chemical_compound ,chemistry ,business.industry ,Environmental health ,Phthalate ,General Earth and Planetary Sciences ,Medicine ,business ,General Environmental Science - Published
- 2021
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16. Modification of the effects of prenatal manganese exposure on child neurodevelopment by maternal anemia and iron deficiency
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Andrea A. Baccarelli, Robert O. Wright, Alejandra Cantoral, Guadalupe Estrada-Gutierrez, Allison Kupsco, Lourdes Schnaas, Chitra Amarasiriwardena, Katherine Svensson, David C. Bellinger, Martha María Téllez-Rojo, and Ivan Pantic
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Male ,Anemia ,Physiology ,Gestational Age ,Nervous System ,Risk Assessment ,Article ,Hemoglobins ,03 medical and health sciences ,Child Development ,Sex Factors ,0302 clinical medicine ,Pregnancy ,Risk Factors ,030225 pediatrics ,medicine ,Humans ,Prospective Studies ,Child ,Prospective cohort study ,Mexico ,Manganese ,Anemia, Iron-Deficiency ,business.industry ,Pregnancy Complications, Hematologic ,Age Factors ,Gestational age ,Iron deficiency ,medicine.disease ,Child development ,Neurodevelopmental Disorders ,Child, Preschool ,Prenatal Exposure Delayed Effects ,Cord blood ,Ferritins ,Pediatrics, Perinatology and Child Health ,Female ,Hemoglobin ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Background We evaluated: 1) associations of prenatal manganese (Mn) levels with child neurodevelopment at 4 – 6 years; 2) effect modification by maternal anemia and iron deficiency; and 3) sex-specific effects. Methods We measured blood Mn, hemoglobin, and serum ferritin in mothers at the 2nd trimester, 3rd trimester, and at birth, and in cord blood from a prospective birth cohort in Mexico City (n=571). McCarthy Scales of Children’s Abilities were measured at 4 – 6 years. Using linear regression, we estimated associations between prenatal Mn and neurodevelopment, examined anemia and iron deficiency as effect modifiers, and analyzed associations by child sex. Results No direct associations were observed between Mn, anemia, or iron deficiency and McCarthy scales. Second trimester iron deficiency and 3rd trimester anemia modified the effect of Mn on child neurodevelopment. For instance, 2nd trimester Mn was positively associated child memory scores in mother’s with normal ferritin (1.85 (0.02, 3.45), but negatively associated in mother’s with low ferritin (−2.41 (−5.28, 0.47), interaction p value = 0.01), a pattern observed across scales. No effect modification at birth or in cord blood was observed. Conclusions Anemia/iron deficiency during pregnancy may modify Mn impacts on child neurodevelopment, particularly in boys.
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- 2020
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17. Prenatal Metal Concentrations and Childhood Cardiometabolic Risk Using Bayesian Kernel Machine Regression to Assess Mixture and Interaction Effects
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Katherine Svensson, Robert O. Wright, Allison Kupsco, Kasey J. Brennan, Joseph M. Braun, Andrea A. Baccarelli, M.M. Tellez-Rojo, Alison P. Sanders, Guadalupe Estrada-Gutierrez, Emily Oken, Alejandra Cantoral, Marianthi-Anna Kioumourtzoglou, Allan C. Just, and Chitra Amarasiriwardena
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Adult ,Leptin ,Adolescent ,Epidemiology ,Bayesian probability ,Blood Pressure ,Interaction ,01 natural sciences ,Article ,Body Mass Index ,Young Adult ,010104 statistics & probability ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Risk Factors ,Environmental health ,Humans ,Medicine ,Prospective Studies ,030212 general & internal medicine ,0101 mathematics ,Child ,Mexico ,Prenatal exposure ,Triglycerides ,Glycated Hemoglobin ,Cardiometabolic risk ,business.industry ,Bayes Theorem ,medicine.disease ,Regression ,Cholesterol ,Adipose Tissue ,Prenatal Exposure Delayed Effects ,Cardiovascular Diseases ,Metals ,Child, Preschool ,Pregnancy Trimester, Second ,Female ,Adiponectin ,business ,Body mass index - Abstract
BACKGROUND: Trace metal concentrations may affect cardio-metabolic risk, but the role of prenatal exposure is unclear. We examined: 1) the relationship between blood metal concentrations during pregnancy and child cardio-metabolic risk factors; 2) overall effects of metals mixture (essential vs. nonessential); and 3) interactions between metals. METHODS: We measured 11 metals in maternal 2(nd) trimester whole blood in a prospective birth cohort in Mexico City. In children 4–6 years old, we measured body mass index (BMI), percent body fat, and blood pressure (N=609); and plasma hemoglobin A1C (HbA1c) , non-high density lipoprotein (HDL) cholesterol, triglycerides, leptin, and adiponectin (N=411). We constructed cardio-metabolic component scores using age- and sex-adjusted z-scores and averaged five scores to create a global risk score. We estimated linear associations of each metal with individual z-scores and used Bayesian Kernel Machine Regression to assess metal mixtures and interactions. RESULTS: Higher total metals were associated with lower HbA1c, leptin, and systolic blood pressure, and with higher adiponectin and non-HDL cholesterol. We observed no interactions between metals. Higher selenium was associated with lower triglycerides in linear (β=−1.01 z-score units per 1 unit ln(Se), 95%CI = −1.84; −0.18) and Bayesian Kernel Machine Regression models. Manganese was associated with decreased HbA1c in linear models (β = −0.32 and 95% CI: −0.61, −0.03). Antimony and arsenic were associated with lower leptin in Bayesian Kernel Machine Regression models. Essential metals were more strongly associated with cardio-metabolic risk than were nonessential metals. CONCLUSIONS: Low essential metals during pregnancy were associated with increased cardio-metabolic risk factors in childhood.
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- 2019
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18. Human milk extracellular vesicle miRNA expression and associations with maternal characteristics in a population-based cohort from the Faroe Islands
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Pal Weihe, Brent A. Coull, Maria Skaalum Petersen, Andrea A. Baccarelli, Damaskini Valvi, Diddier Prada, Philippe Grandjean, Allison Kupsco, and Lisa Hu
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Adult ,Small RNA ,Denmark ,Science ,Statistics as Topic ,Population ,Disease ,Biology ,Article ,Cohort Studies ,Extracellular Vesicles ,Immune system ,Pregnancy ,microRNA ,Cluster Analysis ,Humans ,Mass index ,education ,Genetics ,education.field_of_study ,Multidisciplinary ,Milk, Human ,Extracellular vesicle ,MicroRNAs ,Gene Ontology ,Gene Expression Regulation ,miRNAs ,Cohort ,Medicine ,Extracellular signalling molecules ,Female ,Biomarkers ,Signal Transduction - Abstract
Human milk plays a critical role in infant development and health, particularly in cognitive, immune, and cardiometabolic functions. Milk contains extracellular vesicles (EVs) that can transport biologically relevant cargo from mother to infant, including microRNAs (miRNAs). We aimed to characterize milk EV-miRNA profiles in a human population cohort, assess potential pathways and ontology, and investigate associations with maternal characteristics. We conducted the first study to describe the EV miRNA profile of human milk in 364 mothers from a population-based mother-infant cohort in the Faroe Islands using small RNA sequencing. We detected 1523 miRNAs with ≥ one read in 70% of samples. Using hierarchical clustering, we determined five EV-miRNA clusters, the top three consisting of 15, 27 and 67 miRNAs. Correlation coefficients indicated that the expression of many miRNAs within the top three clusters was highly correlated. Top-cluster human milk EV-miRNAs were involved in pathways enriched for the endocrine system, cellular community, neurodevelopment, and cancers. miRNA expression was associated with time to milk collection post-delivery, maternal body mass index, and maternal smoking, but not maternal parity. Future studies investigating determinants of human EV-miRNAs and associated health outcomes are needed to elucidate the role of human milk EV-miRNAs in health and disease.
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- 2021
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19. Prenatal phthalates, gestational weight gain, and long-term weight changes among Mexican women
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Andrea L. Deierlein, Haotian Wu, Allan C. Just, Allison J. Kupsco, Joseph M. Braun, Emily Oken, Diana C. Soria-Contreras, Alejandra Cantoral, Ma Luisa Pizano, Nia McRae, Martha M. Téllez-Rojo, Robert O. Wright, and Andrea A. Baccarelli
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Pregnancy ,Phthalic Acids ,Humans ,Bayes Theorem ,Environmental Pollutants ,Female ,Mexico ,Biochemistry ,Article ,Gestational Weight Gain ,General Environmental Science - Abstract
BACKGROUND: Phthalates are endocrine disrupting chemicals that may influence weight status; however, few studies have considered weight gain during pregnancy and subsequent long-term weight changes in women. OBJECTIVE: To determine associations of prenatal phthalate exposure with maternal weight during pregnancy and through up to seven years post-delivery. METHODS: We analyzed 15 urinary phthalate biomarker concentrations during the 2(nd) and 3(rd) trimesters among 874 pregnant women enrolled in the Programming Research in Obesity, Growth Environment and Social Stress Study in Mexico City. We examined three time-specific maternal weight outcomes: gestational weight gain (between 2(nd) and 3(rd) trimesters), short-term weight (between 3(rd) trimester and 12 months post-delivery), and long-term weight (between 18 months and 6 – 7 years post-delivery). We used Bayesian Kernel Machine Regression (BKMR) to estimate associations for the total phthalate mixture, as well as multivariable linear mixed models for individual phthalate biomarkers. RESULTS: As a mixture, 2(nd) trimester urinary phthalate biomarker concentrations were associated with somewhat lower gestational weight gain between the 2(nd) and 3(rd) trimesters (interquartile range, IQR, difference: −0.07 standard deviations, SD; 95% credible interval, CrI: −0.20, 0.06); multivariable regression and BKMR models indicated that this inverse association was primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP). Prenatal (2(nd) and 3(rd) trimesters) urinary phthalate mixture concentrations were positively associated with maternal weight change through 12 months postpartum (IQR difference: 0.11 SD; 95% CrI: 0.00, 0.23); these associations persisted from 18 months to 6–7 years follow-up (IQR difference: 0.07 SD; 95% CrI: 0.04, 0.10). Postpartum weight changes were associated with mono-3-carboxypropyl phthalate (MCPP) and MECPTP. CONCLUSIONS: Prenatal phthalate exposure was inversely associated with gestational weight gain and positively associated with long-term changes in maternal weight. Further investigation is required to understand how phthalates may influence body composition and whether they contribute to the development of obesity and other cardiometabolic diseases in women.
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- 2022
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20. Associations of breast milk extracellular vesicle microRNAs with perfluoroalkyl substances in a mother-infant cohort from the Faroe Islands
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Pal Weihe, Andrea A. Baccarelli, Allison Kupsco, Philippe Grandjean, M. Skaalum Petersen, Damaskini Valvi, Lisa Hu, Diddier Prada, and Brent A. Coull
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microRNA ,Cohort ,Mother infant ,General Earth and Planetary Sciences ,Physiology ,Extracellular vesicle ,Breast milk ,Biology ,General Environmental Science - Published
- 2020
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21. Associations of smoking and air pollution with peripheral blood RNA N
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Allison, Kupsco, Gwendolyn, Gonzalez, Brennan H, Baker, Julia M, Knox, Yinan, Zheng, Sheng, Wang, Dou, Chang, Joel, Schwartz, Lifang, Hou, Yinsheng, Wang, and Andrea A, Baccarelli
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Male ,Air Pollutants ,China ,Adenosine ,Smoking ,Environmental Exposure ,Article ,Motor Vehicles ,Air Pollution ,Beijing ,Tobacco Smoking ,Humans ,RNA ,Particulate Matter - Abstract
BACKGROUND: Post-transcriptional modifications of RNA constitute fundamental mechanisms of gene regulation. N(6)-methyladenosine (m(6)A) is critical for health and disease and is modulated by cellular stressors. However, associations between environmental exposures and m(6)A have not been studied in humans. We aimed to examine associations between tobacco smoking and particulate air pollution with m(6)A and mRNA expression levels of its reader, writer and eraser (RWE) genes in blood. METHODS: Using the Beijing Truck Driver Air Pollution Study, we investigated global m(6)A in RNA from peripheral blood collected from 106 human subjects in Beijing, China, in 2008. We measured m(6)A with nano-flow liquid chromatography-tandem mass spectrometry and investigated gene expression of six m(6)A RWEs with real-time-quantitative PCR. Using linear models, we examined associations with smoking status, pack-years, and smoking on day of visit in men, and with environmental tobacco smoke in nonsmokers. We also examined associations with ambient PM(10) (particulate matter ≤ 10 μm in diameter), and personal black carbon (BC) and PM(2.5) measured with a portable monitor. RESULTS: Smoking in men was significantly associated with a relative 10.7% decrease in global m(6)A levels in comparison to nonsmokers (p = 0.02). In men, smoking greater than 3.8 pack-years was associated with a 14.9% lower m(6)A than in nonsmokers. BC exposure trended towards positive associations with m(6)A (5.95% per 10 μg/m(3) increase in BC; 95% CI: −0.96, 13.3). Global m(6)A levels were not correlated with RWE gene expression levels. No associations were detected between smoking or air pollutants and m(6)A RWE gene expression. DISCUSSION: m(6)A was negatively associated with long-term smoking, yet positively associated with short-term BC exposure. These results indicate variable m(6)A responses to environmental stressors, providing early evidence into the impacts of toxicants on RNA modifications and suggesting potential for m(6)A as a biomarker or mechanism in environmental health research.
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- 2020
22. Marine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands
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Allison Kupsco, Pal Weihe, Maria Skaalum Petersen, Lisa Hu, Jenny Jyoung Lee, Andrea A. Baccarelli, Diddier Prada, Philippe Grandjean, Damaskini Valvi, and Brent A. Coull
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Mothers ,Physiology ,Biology ,Article ,Extracellular Vesicles ,Pregnancy ,microRNA ,Humans ,GE1-350 ,Child ,General Environmental Science ,Pollutant ,Milk, Human ,Persistent organic pollutants ,Confounding ,Infant, Newborn ,Bayes Theorem ,Mercury ,Extracellular vesicle ,Pesticide ,Environmental sciences ,MicroRNAs ,Perfluoroalkyl substances ,Cohort ,Environmental Biomarkers ,Gestation ,Birth Cohort ,Environmental Pollutants ,Female - Abstract
Background/Aims Early life exposures to marine contaminants can adversely impact child health but modes of action are unclear. Human milk contains extracellular vesicles (EVs) that can transport biologically relevant cargo from mother to infant, including microRNAs (miRNAs), and may partly mediate the effects of pollutants on child health. However, the role of marine pollutants on miRNA expression in milk EVs is unexplored. Methods We isolated EV RNA from 333 milk samples collected between 2 and 74 days postpartum from a Faroese birth cohort born 1997–2000 and sequenced 2083 miRNAs using a targeted library preparation method. We quantified five perfluoroalkyl substances (PFAS), pesticide metabolite p,p’-dichlorodiphenyldichloroethylene (DDE), and the sum of three major polychlorinated biphenyls (ΣPCBs) in maternal serum at 34 weeks of gestation and maternal hair total mercury (Hg) at birth. We used negative binomial regressions to estimate associations between individual pollutants and 418 reliably expressed EV-miRNAs adjusted for potential confounders. We performed sparse principal components (PCs) analysis to derive the first four components of the EV-miRNA data and examined associations between pollutants and PCs using Bayesian kernel machine regression (BKMR). Results We observed no associations between pollutants and individual EV-miRNA expression after controlling the false discovery rate at 0.1. However, BKMR suggested that Hg was positively associated with PC1 and negatively associated with PC3, while ΣPCBs was negatively associated with PC3, and two PFAS were associated with PC4. Exploration of PC loadings followed by pathway analyses suggested that miRNAs in PC1 (miR-200b-3p, miR-664a-3p, miR-6738-5p, miR-429, miR-1236-5p, miR-4464, and miR-30b-5p) may be related to Hg neurotoxicity, while remaining PCs require further research. Conclusions Our findings suggest that groups of milk EV-miRNAs may better serve as environmental biomarkers than individual miRNAs. Future studies are needed to elucidate the role of milk EV-miRNAs in child health following prenatal exposures.
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- 2022
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23. Vitellogenin levels and others biomarkers show evidences of endocrine disruption in fish species from Iguaçu River - Southern Brazil
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A. Kupsco, C.A. Oliveira Ribeiro, Juan Ramon Esquivel Garcia, and F.Y. Yamamoto
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Male ,0301 basic medicine ,Environmental Engineering ,Estrone ,Health, Toxicology and Mutagenesis ,Fish species ,Sewage ,Zoology ,Endocrine System ,Endocrine Disruptors ,010501 environmental sciences ,Biology ,01 natural sciences ,Vitellogenins ,03 medical and health sciences ,Vitellogenin ,Rivers ,Geophagus ,Animals ,Environmental Chemistry ,Endocrine system ,Gonads ,0105 earth and related environmental sciences ,Estradiol ,business.industry ,Ecology ,Reproduction ,Aquatic ecosystem ,Fishes ,Public Health, Environmental and Occupational Health ,Cichlids ,General Medicine ,General Chemistry ,biology.organism_classification ,Pollution ,Astyanax bifasciatus ,Gonadosomatic Index ,030104 developmental biology ,biology.protein ,Female ,business ,Biomarkers ,Brazil ,Water Pollutants, Chemical ,Environmental Monitoring - Abstract
The adverse effects of endocrine disrupting chemicals (EDCs) on aquatic wildlife and human health represent a current issue of high public concern. Even so, they are still poorly studied in aquatic environments of South America. The aim of the present study was to investigate the impact of EDCs in five cascading reservoirs from the Iguacu River, evaluating reproductive endpoints in three native fish species (Astyanax bifasciatus, Chrenicicla iguassuensis and Geophagus brasiliensis). Additionally, a polyclonal antiserum anti-vitellogenin from G. brasiliensis and a capture ELISA assay were developed for detection of estrogenic or anti-estrogenic activities in male and female fish, respectively. Vitellogenin (VTG) levels in male fish from the Iguacu River was observed, as well as decreased levels of vitellogenin and estradiol in the plasma of female fish. These findings were associated with immature gonads and lower gonadosomatic index in G. brasiliensis adult females from the Foz do Areia (FA) Reservoir. Additionally, both endemic species (Astyanax bifasciatus and Chrenicicla iguassuensis) displayed immature gonads and histological changes, such as degeneration of germ cells, in other studied reservoirs. The current results suggest that these reproductive responses may be associated with the bioavailability of EDCs in the Iguacu River. These impacts are likely related to chemicals released by human activities, especially from sewage and industrial sources and agricultural production, detected in previous studies. Overall, the FA reservoir was potentially the most affected by chemicals with endocrine properties, and further studies are necessary to identify and quantify these chemicals.
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- 2017
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24. Trends and Patterns of Phthalates and Phthalate Alternatives Exposure in Pregnant Women from Mexico City during 2007-2010
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Adriana Mercado-García, Allison Kupsco, Haotian Wu, Emily Oken, Robert O. Wright, Andrea A. Baccarelli, Alejandra Cantoral, Martha María Téllez-Rojo, Joseph M. Braun, Andrea Deierlein, Antonia M. Calafat, and Allan C. Just
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Metabolite ,Pregnancy Trimester, Third ,Phthalic Acids ,Urine ,010501 environmental sciences ,01 natural sciences ,Article ,Cohort Studies ,chemistry.chemical_compound ,Pregnancy ,Environmental health ,Biomonitoring ,medicine ,Environmental Chemistry ,Humans ,Mexico ,0105 earth and related environmental sciences ,business.industry ,Phthalate ,Reproducibility of Results ,General Chemistry ,Environmental exposure ,Environmental Exposure ,medicine.disease ,chemistry ,Cohort ,Environmental Pollutants ,Female ,business ,Cohort study - Abstract
Phthalates are associated with several adverse health outcomes, but few studies have evaluated phthalate exposures in Mexican populations, particularly pregnant women. Between 2007 and 2011, 948 pregnant women from Mexico City were recruited as part of the PROGRESS cohort. We quantified 17 metabolites of phthalates and phthalate alternatives in urine samples collected during the second and third trimesters and examined temporal trends of metabolite concentrations, within-person reproducibility, and relations of individual metabolites with sociodemographic, lifestyle, and occupational factors. Concentrations of mono-2-ethyl-5-carboxypentyl terephthalate, a metabolite of the alternative phthalate di-2-ethylhexyl terephthalate, increased monotonically from 2007 to 2010 (31% per year; 95% confidence interval = 23 and 39%). We observed moderate to high correlations among metabolites collected at the same visit, but there was high variability between second and third trimester phthalate metabolite concentrations (intraclass correlation coefficients = 0.17-0.35). In general, higher socioeconomic status was associated with higher phthalate concentrations. Some metabolites were associated with maternal age and education, but no consistent patterns were observed. Women working in the home and those who worked in administration had higher concentrations of several phthalate metabolites relative to students, professionals, and those in customer service. Biomonitoring efforts are warranted to investigate present and future exposure trends and patterns.
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- 2020
25. Developmental expression and regulation of flavin-containing monooxygenase by the unfolded protein response in Japanese medaka (Oryzias latipes)
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Daniel Schlenk and Allison Kupsco
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Fish Proteins ,0301 basic medicine ,Embryo, Nonmammalian ,Time Factors ,animal structures ,Physiology ,Organogenesis ,Health, Toxicology and Mutagenesis ,Oryzias ,ved/biology.organism_classification_rank.species ,Flavin-containing monooxygenase ,Toxicology ,Biochemistry ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,chemistry.chemical_compound ,Gene expression ,Animals ,RNA, Messenger ,Promoter Regions, Genetic ,Model organism ,Genetics ,Binding Sites ,biology ,ved/biology ,Tunicamycin ,Endoplasmic reticulum ,Gene Expression Regulation, Developmental ,Cell Biology ,General Medicine ,Japanese Medaka ,biology.organism_classification ,Cell biology ,Dithiothreitol ,030104 developmental biology ,Liver ,chemistry ,embryonic structures ,Oxygenases ,Unfolded Protein Response ,Unfolded protein response ,Transcription Factors - Abstract
Flavin-containing monooxygenases (FMOs) play a key role in xenobiotic metabolism, are regulated by environmental conditions, and are differentially regulated during mammalian development. Japanese medaka (Oryzias latipes) are a common model organism for toxicological studies. The goal of the current research was to characterize developmental expression and regulation of FMOs in Japanese medaka embryos to better understand the role of FMOs in this model species. Five putative medaka fmos were characterized from the medaka genome through the National Center for Biotechnology Information (NCBI) database by protein motifs and alignments, then identified as fmo4, fmo5A, fmo5B, fmo5C and fmo5D for the current study. Fmo gene expression was analyzed at 1 dpf, 3 dpf, 6 dpf and 9 dpf and distinct developmental patterns of expression were observed. Fmo4 and fmo5D increased 3-fold during mid organogenesis (6 dpf), while fmo5B and fmo5C decreased significantly in early organogenesis (3 dpf) and fmo5A was unaltered. Promoter analysis was performed for transcription factor binding sites and indicated regulation by developmental factors and a role for the unfolded protein response in fmo modulation. Fmo regulation by the UPR was assessed with treatments of 1 μg/ml, 2 μg/ml, and 4 μg/ml Tunicamycin (Tm), and 2 mM and 4 mM dithiothreitol (DTT), well-known inducers of endoplasmic reticulum stress, for 24 h from 5–6 dpf. High concentrations to Tm induced fmo4 and fmo5A up to two-fold, while DTT significantly decreased expression of fmo5A, fmo5B, and fmo5C. Results suggest that medaka fmos are variably regulated by the UPR during organogenesis with variable developmental expression, and suggesting potential stage-dependent activation or detoxification of xenobiotics.
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- 2017
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26. Influence of Temperature on the Thyroidogenic Effects of Diuron and Its Metabolite 3,4-DCA in Tadpoles of the American Bullfrog (Lithobates catesbeianus)
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Andréia Arantes Felício, Allison Kupsco, Daniel Schlenk, Graciel Diamante, Juliane Silberschmidt Freitas, and Eduardo Alves de Almeida
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0301 basic medicine ,media_common.quotation_subject ,Metabolite ,Zoology ,010501 environmental sciences ,01 natural sciences ,Freshwater ecosystem ,Aquatic organisms ,03 medical and health sciences ,chemistry.chemical_compound ,Bullfrog ,Animals ,Environmental Chemistry ,Metamorphosis ,0105 earth and related environmental sciences ,media_common ,Larva ,Rana catesbeiana ,biology ,Ecology ,Lithobates ,Metamorphosis, Biological ,Temperature ,General Chemistry ,biology.organism_classification ,030104 developmental biology ,chemistry ,Diuron ,Thyroid function - Abstract
Temperature is a key variable affecting the timing of amphibian metamorphosis from tadpoles to tetrapods, through the production and subsequent function of thyroid hormones (TH). Thyroid function can be impaired by environmental contaminants as well as temperature. Tadpoles can experience large temperature fluctuations in their habitats and many species are distributed in areas that may be impacted by agriculture. Diuron is a widely used herbicide detected in freshwater ecosystems and may impact endocrine function in aquatic organisms. We evaluated the influence of temperature (28 and 34 °C) on the action of diuron and its metabolite 3,4-dichloroaniline (3,4-DCA) on thyroid function and metamorphosis in tadpoles of Lithobates catesbeianus. Exposure to both compounds induced more pronounced changes in gene expression and plasma 3,3′,5-triiodothyronine (T3) concentrations in tadpoles treated at higher temperature. T3 concentrations were increased in tadpoles exposed to 200 ng/L of diuron at 34 °C and an acc...
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- 2016
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27. Molecular mechanisms of selenium-Induced spinal deformities in fish
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Allison Kupsco and Daniel Schlenk
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Fish Proteins ,0301 basic medicine ,Programmed cell death ,Embryo, Nonmammalian ,Health, Toxicology and Mutagenesis ,Oryzias ,Protein Disulfide-Isomerases ,Gene Expression ,Apoptosis ,Core Binding Factor Alpha 1 Subunit ,Aquatic Science ,Biology ,medicine.disease_cause ,Bone and Bones ,Selenium ,03 medical and health sciences ,chemistry.chemical_compound ,Gene expression ,medicine ,Animals ,Selenomethionine ,Protein disulfide-isomerase ,Tunicamycin ,Cell biology ,Oxidative Stress ,030104 developmental biology ,chemistry ,Biochemistry ,Toxicity ,Unfolded Protein Response ,Unfolded protein response ,Female ,Water Pollutants, Chemical ,Oxidative stress ,Molecular Chaperones - Abstract
Selenium toxicity to oviparous vertebrates is often attributed to selenomethionine (SeMet), which can biomagnify through maternal transfer. Although oxidative stress is implicated in SeMet toxicity, knowledge gaps remain in how SeMet causes characteristic spinal deformities. In the present study, we use the Japanese medaka (Oryzias latipes) model to investigate the role of oxidative stress, cell death, and the unfolded protein response (UPR) on skeletal gene expression and SeMet toxicity, linking localization of cellular effects to observed abnormalities. Medaka embryos were treated with 2.5 μM or 5 μM SeMet for 24 h at stage 25 (48 h post fertilization). Post treatment, embryos were separated into normal, deformed (mild, moderate or severe), or dead categories. Dichlorofluorescein staining demonstrated oxidative stress in tails of embryos with observable spinal malformations. Furthermore, acridine orange staining for apoptosis identified significantly more dead cells in tails of treated embryos. Gene expression studies for the UPR suggest a potential role for CHOP (c/ebp homologous protein) induced apoptosis deformed embryos after 5 μM SeMet, accompanied by a significant decrease in PDIA4 (protein disulfide isomerase A4) and no change in Dnajb9 (ER DNA J Domain-Containing Protein 4). This expression was distinct from the UPR induced by well-studied ER stress inducer, tunicamycin, which robustly activated CHOP, PDIA4 and Dnajb9. Finally, SeMet treatment significantly decreased transcripts of cartilage development, Sox9 (SRY box 9), while increasing Runx2 in deformed embryos, without altering Twist or Collagen 2a1. Results suggest that oxidative stress, the UPR and cell death play key roles in SeMet induced deformities and altered skeletal development factors.
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- 2016
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28. Health Sciences Libraries Forecasting Information Service Trends for Researchers: Models Applicable to All Academic Libraries
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Lynda Jones Hartel, Timothy J. Cain, Jeremy Kupsco, Fern Cheek, and Anna Getselman
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Information management ,Service (business) ,Knowledge management ,Computer science ,business.industry ,Data management ,05 social sciences ,Library and Information Sciences ,050905 science studies ,Data science ,Health science ,Information system ,Digital resources ,State (computer science) ,0509 other social sciences ,050904 information & library sciences ,User needs ,business - Abstract
To better understand the value of current information services and to forecast the evolving information and data management needs of researchers, a study was conducted at two research-intensive universities. The methodology and planning framework applied by health science librarians at Emory University and The Ohio State University focused on identifying the need for new or retooled information services supporting health and biomedical researchers and their increasing use of digital resources. The lessons learned and outcomes described herein are informing the development and implementation of new information service models and can help forecast changing user needs across the broader library community.
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- 2016
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29. Trophic transfer and effects of DDT in male hornyhead turbot (Pleuronichthys verticalis) from Palos Verdes Superfund site, CA (USA) and comparisons to field monitoring
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Wenjian Lao, Keith A. Maruya, Daniel Schlenk, Jordan Crago, Allison Kupsco, Alvine C. Mehinto, Fang Jia, Elvis Genbo Xu, and Jay Gan
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Male ,Geologic Sediments ,Transcription, Genetic ,010504 meteorology & atmospheric sciences ,Health, Toxicology and Mutagenesis ,Estrogenic activity ,Flounder ,Endocrine Disruptors ,010501 environmental sciences ,Toxicology ,01 natural sciences ,California ,Soil ,Flatfish ,Receptors ,Soil Pollutants ,Water Pollutants ,Estradiol ,biology ,Liver Disease ,General Medicine ,Environmental exposure ,Bioaccumulation ,Pollution ,Hornyhead turbot ,Refuse Disposal ,Turbot ,Receptors, Estrogen ,Cell-based bioassay ,Flatfishes ,Transcription ,Environmental Monitoring ,Food Chain ,Zoology ,Chemical ,Article ,DDT ,Genetic ,trophic transfer ,Animals ,Pesticides ,0105 earth and related environmental sciences ,Polychaeta ,Aquatic animal ,Environmental Exposure ,Pesticide ,biology.organism_classification ,Estrogen ,Diet ,Digestive Diseases ,Environmental Sciences ,Water Pollutants, Chemical - Abstract
High concentrations of DDT and metabolites (ΣDDT) have been detected in sediment and the demersal flatfish hornyhead turbot (Pleuronichtys verticalis) collected from Palos Verdes (PV), California, USA, a site contaminated with over 100 metric tons of DDT throughout 1960s-70s. This study was conducted to assess the transfer of ΣDDT from PV-sediment into polychaetes (Neanthes arenaceodentata) and hornyhead turbot, and to investigate if the responses in turbots from two different laboratory exposures mimic those in turbots caught in PV (PV-turbot). Turbot fed PV-sediment-contaminated polychaete for 7 days had liver concentrations of ΣDDT similar to PV-turbot. After 28 days, ΣDDT also accumulated in livers of turbot gavaged with a ΣDDT mixture. Invitro cell bioassays indicated significant increases of 17β-estradiol equivalents (EEQ) in turbot bile extracts as compared to the control in the 7-day study. These responses corresponded to those measured in PV-fish. Glucocorticoid receptor (GR), anti-androgen receptor (anti-AR), estrogen receptor (ER) or aryl hydrocarbon receptor (AhR) activities were also observed in extracts of PV-sediment, and PV-sediment-exposed worm. Anti-AR, AhR and GR activities were significantly higher in PV-sediment than reference sediment (San Diego, SD). Higher transcripts of hepatic VTG, ERα and ERβ were found in PV-turbot than SD-turbot, but were unaltered in fish exposed to sediment-contaminated worms for the 7-day study. In contrast, liver extracts from the 28-day treatment of ΣDDT showed lower EEQ but similar hepatic VTG and ERβ transcripts relative to those of PV-turbot. These data indicated that trophic transfer of sediment-associated DDT in 7-day exposures corresponded to field measurements of DDT residues and invitro ER bioactivities, but failed to mimic invivo biological effects observed in field fish. In contrast, treatment with ΣDDT alone for 28 days mimicked invivo biological effects of DDTs in PV fish, but did not correspond to liver concentrations or invitro bioactivities.
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- 2016
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30. Prenatal manganese and cord blood mitochondrial DNA copy number: Effect modification by maternal anemic status
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Martha María Téllez-Rojo, Ivan Pantic, Chitra Amarasiriwardena, Robert O. Wright, Allison Kupsco, Andrea A. Baccarelli, Lourdes Schnaas, Kasey J. Brennan, Guadalupe Estrada-Gutierrez, Katherine Svensson, and Marco Sanchez-Guerra
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Adult ,Male ,medicine.medical_specialty ,010504 meteorology & atmospheric sciences ,DNA Copy Number Variations ,Anemia ,Pregnancy Trimester, Third ,Mothers ,010501 environmental sciences ,01 natural sciences ,DNA, Mitochondrial ,Article ,Young Adult ,Pregnancy ,Internal medicine ,medicine ,Humans ,Mean corpuscular volume ,Maternal-Fetal Exchange ,Mexico ,lcsh:Environmental sciences ,0105 earth and related environmental sciences ,General Environmental Science ,Whole blood ,lcsh:GE1-350 ,Manganese ,biology ,medicine.diagnostic_test ,business.industry ,Infant, Newborn ,Iron deficiency ,medicine.disease ,Fetal Blood ,Ferritin ,Endocrinology ,Cord blood ,biology.protein ,Environmental Pollutants ,Female ,Hemoglobin ,business - Abstract
Introduction: Manganese (Mn) is an essential nutrient but also a toxicant at high exposures, when it can induce oxidative stress (OS). Mn uptake is inversely correlated with iron status, therefore anemic individuals may be more susceptible to Mn overload induced-OS, which can manifest as changes in mitochondrial DNA copy number (mtDNA CN). Our objectives were to: 1) determine stage-specific associations of prenatal Mn exposure with cord blood MtDNA CN; and 2) investigate effect modification by maternal anemia, ferritin, and mean corpuscular volume (MCV). Materials and methods: We measured whole blood Mn, hemoglobin, serum ferritin, and MCV in the 2nd and 3rd trimester, in maternal blood at birth, and in cord blood from a prospective birth cohort in Mexico City, Mexico (n = 485). We then extracted DNA from cord blood leukocytes to determine mtDNA CN. We used robust regression to measure associations between Mn and mtDNA CN at each trimester and at birth. Anemia (hemoglobin ≤11 g/dL), iron deficiency (ferritin ≤15 ng/mL) and MCV (stratified at median), were examined as effect modifiers. Results: Mn levels increased throughout pregnancy, and Mn was inversely correlated with ferritin. We observed a positive association between Mn in the 3rd trimester and Mn in cord blood and mtDNA CN (β = 0.04–0.05; 95% CI = 0.01, 0.08). Anemia significantly modified the association between mtDNA CN and Mn in the 2nd trimester. We found a positive association between 2nd trimester Mn and mtDNA CN in mothers with normal hemoglobin, and a negative association in those with low hemoglobin. (βhigh = 0.06; 95% CI = 0.01, 0.11; p = 0.01 and βlow = −0.06; 95% CI = 0.03, −0.13; p = 0.06). No associations were detected between anemia, iron deficiency and MCV and mtDNA CN. Conclusions: Maternal blood Mn in the 3rd trimester and in cord blood was positively associated with mtDNA CN, suggesting that higher late pregnancy prenatal Mn exposures can impact newborn mitochondria by promoting OS. Furthermore, 2nd trimester Mn was positively associated with mtDNA in non-anemic mother-child pairs but inversely associated in anemic individuals, indicating potential interactions between Mn and chronic anemia. Keywords: Prenatal exposure, Manganese, Anemia, Iron deficiency, Mitochondria, Mitochondrial DNA
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- 2018
31. Associations of prenatal urinary phthalates, gestational weight gain, and postpartum weight retention among pregnant women from Mexico City
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Allan C. Just, M.M. Tellez-Rojo, Andrea A. Baccarelli, McRae N, Antonia M. Calafat, Alejandra Cantoral, Andrea Deierlein, Allison Kupsco, Wu H, and Soria D
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Global and Planetary Change ,medicine.medical_specialty ,Epidemiology ,Obstetrics ,business.industry ,Health, Toxicology and Mutagenesis ,Urinary system ,Public Health, Environmental and Occupational Health ,Pollution ,Mexico city ,medicine ,Gestation ,medicine.symptom ,business ,Weight retention ,Weight gain - Published
- 2019
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32. Prenatal Phthalates Exposure and Childhood Adiposity, Adipokines, and Lipid Profiles at 48 and 72 months
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Téllez M, Oken E, Baccarelli A, Tolentino M, Wright R, Allison Kupsco, Calafat A, Braun J, Wu H, and Just A
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Global and Planetary Change ,medicine.medical_specialty ,Endocrinology ,Epidemiology ,business.industry ,Health, Toxicology and Mutagenesis ,Internal medicine ,Public Health, Environmental and Occupational Health ,medicine ,Adipokine ,business ,Pollution - Published
- 2019
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33. Associations of prenatal urinary phthalates and blood pressure during pregnancy
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Katherine Svensson, M.M. Tellez-Rojo, Andrea Deierlein, Andrea A. Baccarelli, Alison P. Sanders, Allan C. Just, Ivan Pantic, Wu H, Antonia M. Calafat, and Allison Kupsco
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Global and Planetary Change ,Pregnancy ,medicine.medical_specialty ,Epidemiology ,business.industry ,Obstetrics ,Health, Toxicology and Mutagenesis ,Urinary system ,Public Health, Environmental and Occupational Health ,medicine.disease ,Pollution ,Blood pressure ,medicine ,business - Published
- 2019
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34. Prevalence of publishing in predatory journals
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Powell, Kim and Kupsco, Jeremy
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Objectives: In 2017 the journal Nature published challenges to the assumption that research intensive U.S. institutions are immune to the hazards of predatory publishing. Sample articles from hundreds of potentially predatory journals were analyzed: the NIH was the most frequent funder and Harvard was among the most frequent institutions. Our study was designed to identify the publication prevalence at our institution. Methods: Predatory publishers were defined using an archived version of Beall’s list, a now defunct website that was widely recognized as the only comprehensive black list for potential predators. The archive was collected January 15, 2017 and reflects updates made 1-2 weeks prior. To identify our NIH publications, records were collected from PubMed Central using an institution search and limiting to 2011-2016 to reflect a five-year period covered by Beall’s last update. PMC was selected under the assumption that direct journal inclusion in PubMed/MedLine serves as a proxy for quality. Journal and ISSN data were referenced against Ulrich’s Periodical Directory to determine publishers. Data were then compared against the Beall’s listing of potentially predatory publishers and standalone journals. The publication costs for the predatory journals were used to determine the total amount of NIH funding used to pay for publications in predatory journals. Results: The review of the University’s Publications submitted to PubMed Central from 2011 to 2016 revealed 15090 publications. Of those 15090 articles 218 publications (1.4%) were from publishers that fell in Beall’s list of predatory publishers. A review of publication fees for the publishers that University faculty published in revealed that approximately $300,000 dollars of Federal grant money was spent over the 5 year period publishing in predatory publications. Conclusions: Previously, it was thought that publishing predatory journals was primarily a problem in developing countries. However, like the 2017 Nature study, we found that researchers publishing at Emory are publishing in journals that are considered predatory. While the rate of publication in predatory journals is low (1.4%) it did cost approximately $300,000 of Federal tax payer money, which amounts to approximately 70% of the funds of one year of the average NIH R01 grant.
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- 2018
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35. The effect of chlorpyrifos on salinity acclimation of juvenile rainbow trout (Oncorhynchus mykiss)
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Allison Kupsco, Bagher Mojazi Amiri, Mahbubeh Hoseinzadeh, Daniel Schlenk, Elvis Genbo Xu, and Marissa Giroux
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0301 basic medicine ,Fish Proteins ,Gills ,Salinity ,Hydrocortisone ,Health, Toxicology and Mutagenesis ,Acclimatization ,010501 environmental sciences ,Aquatic Science ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Animal science ,Animals ,RNA, Messenger ,0105 earth and related environmental sciences ,biology ,Organophosphate ,biology.organism_classification ,Hormones ,Trout ,Thyroxine ,030104 developmental biology ,chemistry ,Gene Expression Regulation ,Oncorhynchus mykiss ,Toxicity ,Osmoregulation ,Triiodothyronine ,Rainbow trout ,Chlorpyrifos ,Xenobiotic ,Water Pollutants, Chemical - Abstract
As a part of their unique life cycle, most salmonids undergo a transition from fresh water to salt water requiring various adjustments in metabolism, osmoregulation and ion regulation. Exposure to pesticides may affect the acclimation of juvenile salmonids to salt water during downstream migration to estuaries. Using the Caspian Sea as a model waterbody, the present study aimed to determine how the toxicity of the organophosphate pesticide chlorpyrifos (CPF) impacts saline acclimation of rainbow trout (Oncorhynchus mykiss). We pre-exposed 4-month-old fish to nominal concentrations of 0, 20, 40, 80, 160 μg/L of CPF for seven days, and then gradually to salinity (12 ppt) for another seven days. Mortality, levels of cortisol, T3 and T4 in serum, and expression of genes involved in gill ion transport (Na+/K+ATPase α1a and α1b) and liver xenobiotic detoxification (Glutathione-S-Transferase pi, GST) were measured at day fourteen. Cortisol concentrations in serum were not changed by CPF exposure in freshwater, but serum T3 increased up to three fold relative to controls in freshwater. Following salinity acclimation, T3 and T4 concentrations in the serum were both increased up to 2.5 and 8.8 fold in animals treated with CPF followed by saltwater. Na+/K + ATPase α1a and α1b mRNA in gill were unchanged by CPF treatment in freshwater but trended higher in CPF-treated animals after salinity acclimation. Hepatic mRNA of GST was significantly increased following exposure to CPF but was unchanged after saltwater exposure. Although saltwater treatment reduced the acute lethality of CPF, changes in T3/T4 suggest sublethal impacts may occur in CPF-treated fish after they acclimate to Caspian seawater.
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- 2017
36. Dynamic Alterations in DNA Methylation Precede Tris(1,3-dichloro-2-propyl)phosphate-Induced Delays in Zebrafish Epiboly
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Christine C. Nguyen, Allison Kupsco, David C. Volz, and Subham Dasgupta
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0301 basic medicine ,Tris ,animal structures ,Environmental Engineering ,Environmental Science and Management ,Health, Toxicology and Mutagenesis ,Tris(1,3-dichloro-2-propyl)phosphate ,Epiboly ,010501 environmental sciences ,Biology ,01 natural sciences ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Environmental Biotechnology ,Genetics ,Environmental Chemistry ,2.2 Factors relating to the physical environment ,Aetiology ,Waste Management and Disposal ,Zebrafish ,0105 earth and related environmental sciences ,Water Science and Technology ,Ecology ,Embryo ,Methylation ,biology.organism_classification ,Pollution ,Molecular biology ,Bisulfite ,030104 developmental biology ,chemistry ,embryonic structures ,DNA methylation - Abstract
Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) is an organophosphate flame retardant that impacts zebrafish epiboly – an effect that may be associated with genome-wide hypomethylation. Using zebrafish as a model, the objectives of this study were to (1) quantify concentration-dependent impacts of TDCIPP on epiboly; (2) determine whether co-exposure with folic acid (FA) – a methyl donor – mitigates TDCIPP-induced impacts; and (3) using ten previously identified TDCIPP-susceptible loci, rely on bisulfite amplicon sequencing (BSAS) to monitor CpG methylation dynamics across multiple TDCIPP concentrations in the presence or absence of FA. Embryos were exposed to TDCIPP from 0.75 h post-fertilization (hpf) to 2, 4, 6, or 24 hpf in the presence or absence of 1 mM FA. Although TDCIPP delayed epiboly up to 3 h by 6 hpf and induced malformations by 24 hpf, FA was unable to mitigate TDCIPP-induced effects at all stages evaluated. Moreover, while no differences in global methylation were detected using a 5-methylcytosine (5-mC) DNA ELISA, BSAS revealed that TDCIPP-induced effects on CpG methylation were dependent on concentration and developmental stage, and that early effects on methylation do not persist despite continuous exposure. Our findings demonstrate that TDCIPP delays zebrafish epiboly, a phenotype that is preceded by complex, dynamic alterations in DNA methylation.
- Published
- 2017
37. Effects of Prenatal Air Pollution on Family-Specific, Genome-Wide, Repetitive Element Methylation in Cord Blood
- Author
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Katherine Svensson, Robert O. Wright, Jonathan A Heiss, Téllez Rojo M, Allison Kupsco, Guadalupe Estrada-Gutierrez, Andrea A. Baccarelli, Allan C. Just, and Kasey J. Brennan
- Subjects
Genetics ,Global and Planetary Change ,Epidemiology ,Health, Toxicology and Mutagenesis ,Cord blood ,Public Health, Environmental and Occupational Health ,Methylation ,Biology ,Pollution ,Genome ,Repetitive Element - Published
- 2019
- Full Text
- View/download PDF
38. Stage susceptibility of Japanese medaka (Oryzias latipes) to selenomethionine and hypersaline developmental toxicity
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Allison Kupsco and Daniel Schlenk
- Subjects
0301 basic medicine ,Salinity ,Embryo, Nonmammalian ,Health, Toxicology and Mutagenesis ,Oryzias ,Developmental toxicity ,chemistry.chemical_element ,Embryonic Development ,Fresh Water ,010501 environmental sciences ,Biology ,01 natural sciences ,Article ,Toxicology ,Andrology ,03 medical and health sciences ,Selenium ,Environmental Chemistry ,Climate change ,Animals ,Selenomethionine ,0105 earth and related environmental sciences ,Mixture toxicity ,Nonmammalian ,Prevention ,Embryogenesis ,Embryo ,Japanese Medaka ,Biological Sciences ,biology.organism_classification ,030104 developmental biology ,chemistry ,Bioaccumulation ,Toxicity ,Chemical Sciences ,Environmental Sciences - Abstract
Anthropogenic disturbance of seleniferous soils can lead to selenium contamination of waterways. Although selenium is an essential micronutrient, bioaccumulation and maternal transfer of proteinaceous selenomethionine (SeMet) can result in embryo toxicity. Furthermore, as the climate changes, the salinity of spawning grounds in water-restrained estuaries is increasing. Although a small increase in salinity may not directly impact adult fish, it may alter the detoxification strategies of developing organisms. Previous research indicates that hypersalinity may potentiate SeMet embryo toxicity at an early developmental stage. However, embryonic development is a complex, spatiotemporal process with a constantly shifting cellular microenvironment. To generate thresholds and an adverse outcome pathway for the interactions between selenium and salinity, we sought to identify windows of susceptibility for lethality and deformities in the Japanese medaka (Oryzias latipes). Embryos were treated in freshwater or saltwater for 24 h with 0.5 µM, 5 µM, and 50 µM SeMet at 6 different developmental stages (9, 17, 25, 29, 34, and 38). Survival, hatch, deformities (total, type, and severity), and days to hatch were quantified. Selenium embryo tissue measurements were performed. Selenomethionine exposures of 5 µM and 50 µM significantly decreased survival and hatch at all stages. However, SeMet uptake was stage-dependent and increased with stage. Stage 17 (early neurulation) was identified as the most susceptible stage for lethality and deformities. Selenomethionine in saltwater caused significantly greater toxicity than freshwater at stage 25 (early organogenesis), suggesting a role for liver and osmoregulatory organogenesis in toxicity.
- Published
- 2015
39. Genetic and biochemical characterization ofDrosophilaSnipper: A promiscuous member of the metazoan 3′hExo/ERI-1 family of 3′ to 5′ exonucleases
- Author
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Roopa Thapar, William F. Marzluff, Robert J. Duronio, Jeremy M. Kupsco, and Ming Jing Wu
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Exonucleases ,G2 Phase ,Exonuclease ,Molecular Sequence Data ,Mutant ,Apoptosis ,Biology ,Article ,S Phase ,Substrate Specificity ,Histones ,Histone H3 ,RNA interference ,Animals ,Drosophila Proteins ,SNP ,Amino Acid Sequence ,RNA, Messenger ,Molecular Biology ,Gene ,Genetics ,Deoxyribonucleases ,Sequence Homology, Amino Acid ,Gene Expression Regulation, Developmental ,RNA ,Recombinant Proteins ,Drosophila melanogaster ,Histone ,Mutation ,biology.protein ,RNA Interference - Abstract
The DnaQ-H family exonuclease Snipper (Snp) is a 33-kDaDrosophila melanogasterhomolog of 3′hExo and ERI-1, exoribonucleases implicated in the degradation of histone mRNA in mammals and in the negative regulation of RNA interference (RNAi) inCaenorhabditis elegans, respectively. In metazoans, Snp, Exod1, 3′hExo, ERI-1, and the prpip nucleases define a new subclass of structure-specific 3′-5′ exonucleases that bind and degrade double-stranded RNA and/or DNA substrates with 3′ overhangs of 2–5 nucleotides (nt) in the presence of Mg2+with no apparent sequence specificity. These nucleases are also capable of degrading linear substrates. Snp efficiently degrades structured RNA and DNA substrates as long as there exists a minimum 3′ overhang of 2 nt to initiate degradation. We identified aSnpmutant and used it to test whether Snp plays a role in regulating histone mRNA degradation or RNAi in vivo.Snpmutant flies are viable, and display no obvious developmental abnormalities. The expression pattern and level of histone H3 mRNA inSnpmutant embryos and third instar imaginal eye discs was indistinguishable from wild type, suggesting that Snp does not play a significant role in the turnover of histone mRNA at the end of the S phase. The loss ofSnpwas also unable to enhance the silencing capability of two different RNAi transgenes targeting thewhiteandyellowgenes, suggesting that Snp does not negatively modulate RNAi. Therefore, Snp is a nonessential exonuclease that is not a functional ortholog of either 3′hExo or ERI-1.
- Published
- 2006
- Full Text
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40. U7 snRNA mutations in Drosophila block histone pre-mRNA processing and disrupt oogenesis
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Brandon D. Burch, Zbigniew Dominski, William F. Marzluff, Robert J. Duronio, Jeremy M. Kupsco, Ashley C. Godfrey, and Ryan M. Zimmerman
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Molecular Sequence Data ,Genes, Insect ,Article ,Histones ,Oogenesis ,Histone H1 ,RNA, Small Nuclear ,Histone H2A ,RNA Precursors ,Animals ,Drosophila Proteins ,Histone code ,snRNP ,RNA Processing, Post-Transcriptional ,Histone locus body ,Molecular Biology ,SLBP ,Base Sequence ,biology ,RNA-Binding Proteins ,Molecular biology ,Histone ,Histone methyltransferase ,Mutation ,biology.protein ,Drosophila ,Female ,Infertility, Female - Abstract
Metazoan replication-dependent histone mRNAs are not polyadenylated, and instead terminate in a conserved stem–loop structure generated by an endonucleolytic cleavage involving the U7 snRNP, which interacts with histone pre-mRNAs through base-pairing between U7 snRNA and a purine-rich sequence in the pre-mRNA located downstream of the cleavage site. Here we generate null mutations of the single Drosophila U7 gene and demonstrate that U7 snRNA is required in vivo for processing all replication-associated histone pre-mRNAs. Mutation of U7 results in the production of poly A+ histone mRNA in both proliferating and endocycling cells because of read-through to cryptic polyadenylation sites found downstream of each Drosophila histone gene. A similar molecular phenotype also results from mutation of Slbp, which encodes the protein that binds the histone mRNA 3′ stem–loop. U7 null mutants develop into sterile males and females, and these females display defects during oogenesis similar to germ line clones of Slbp null cells. In contrast to U7 mutants, Slbp null mutations cause lethality. This may reflect a later onset of the histone pre-mRNA processing defect in U7 mutants compared to Slbp mutants, due to maternal stores of U7 snRNA. A double mutant combination of a viable, hypomorphic Slbp allele and a viable U7 null allele is lethal, and these double mutants express polyadenylated histone mRNAs earlier in development than either single mutant. These data suggest that SLBP and U7 snRNP cooperate in the production of histone mRNA in vivo, and that disruption of histone pre-mRNA processing is detrimental to development.
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- 2006
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41. DrosophilaStem-Loop Binding Protein Intracellular Localization Is Mediated by Phosphorylation and Is Required for Cell Cycle-regulated Histone mRNA Expression
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William F. Marzluff, Xiao Cui Yang, Zbigniew Dominski, Robert J. Duronio, David J. Lanzotti, and Jeremy M. Kupsco
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Cytoplasm ,Embryo, Nonmammalian ,RNA-binding protein ,Histones ,Histone H1 ,Histone H2A ,RNA Precursors ,Animals ,Drosophila Proteins ,Histone code ,RNA, Messenger ,Phosphorylation ,RNA Processing, Post-Transcriptional ,Molecular Biology ,Cell Nucleus ,SLBP ,biology ,Binding protein ,Cell Cycle ,Gene Expression Regulation, Developmental ,RNA-Binding Proteins ,Articles ,Cell Biology ,Molecular biology ,Cell biology ,Drosophila melanogaster ,Histone ,Histone methyltransferase ,Mutation ,biology.protein - Abstract
Stem-loop binding protein (SLBP) is an essential component of the histone pre-mRNA processing machinery. SLBP protein expression was examined during Drosophila development by using transgenes expressing hemagglutinin (HA) epitope-tagged proteins expressed from the endogenous Slbp promoter. Full-length HA-dSLBP complemented a Slbp null mutation, demonstrating that it was fully functional. dSLBP protein accumulates throughout the cell cycle, in contrast to the observed restriction of mammalian SLBP to S phase. dSLBP is located in both nucleus and cytoplasm in replicating cells, but it becomes predominantly nuclear during G2. dSLBP is present in mitotic cells and is down-regulated in G1 when cells exit the cell cycle. We determined whether mutation at previously identified phosphorylation sites, T120 and T230, affected the ability of the protein to restore viability and histone mRNA processing to dSLBP null mutants. The T120A SLBP restored viability and histone pre-mRNA processing. However, the T230A mutant, located in a conserved TPNK sequence in the RNA binding domain, did not restore viability and histone mRNA processing in vivo, although it had full activity in histone mRNA processing in vitro. The T230A protein is concentrated in the cytoplasm, suggesting that it is defective in nuclear targeting, and accounting for its failure to function in histone pre-mRNA processing in vivo.
- Published
- 2004
- Full Text
- View/download PDF
42. Tris(1,3-dichloro-2-propyl) phosphate disrupts dorsoventral patterning in zebrafish embryos
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Subham Dasgupta, Diego Altomare, Jessica K. Leet, David C. Volz, Allison Kupsco, and Sara M.F. Vliet
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0301 basic medicine ,animal structures ,Morpholino ,Tris(1,3-dichloro-2-propyl)phosphate ,lcsh:Medicine ,Epiboly ,Toxicology ,Ecotoxicology ,Bone morphogenetic protein ,Medical and Health Sciences ,Dorsoventral patterning ,General Biochemistry, Genetics and Molecular Biology ,Flame retardant ,03 medical and health sciences ,chemistry.chemical_compound ,TDCIPP ,Genetics ,Zebrafish ,Public health ,Gene knockdown ,biology ,Chemistry ,General Neuroscience ,lcsh:R ,Embryo ,General Medicine ,Biological Sciences ,biology.organism_classification ,Cell biology ,030104 developmental biology ,embryonic structures ,Chordin ,General Agricultural and Biological Sciences ,Developmental Biology - Abstract
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a high-production volume organophosphate flame retardant widely used within the United States. Within zebrafish, initiation of TDCIPP exposure at 0.75 h post-fertilization (hpf) results in genome-wide alterations in methylation during cleavage (2 hpf) as well as epiboly delay or arrest (at higher concentrations) during late-blastula and early-gastrula (4–6 hpf). To determine whether these TDCIPP-induced effects were associated with impacts on the transcriptome, embryos were exposed to vehicle (0.1% DMSO) or 2 µM TDCIPP from 0.75 hpf to 6 hpf, and total RNA was extracted from triplicate embryo pools per treatment and hybridized onto duplicate Affymetrix Zebrafish Gene 1.0 ST Arrays per RNA sample. Based on transcriptome-wide profiling, TDCIPP resulted in a significant impact on biological processes involved in dorsoventral patterning and bone morphogenetic protein (BMP) signaling. Consistent with these responses, TDCIPP exposure also resulted in strongly dorsalized embryos by 24 hpf—a phenotype that mimicked the effects of dorsomorphin, a potent and selective BMP inhibitor. Moreover, the majority of dorsalized embryos were preceded by epiboly arrest at 6 hpf. Our microarray data also revealed that the expression of sizzled (szl)—a gene encoding a secreted Frizzled-related protein that limits BMP signaling—was significantly decreased by nearly 4-fold at 6 hpf. Therefore, we used a splice-blocking morpholino to test the hypothesis that knockdown ofszlphenocopies TDCIPP-induced delays in epiboly progression. Interestingly, contrary to our hypothesis, injection ofszlMOs did not affect epiboly progression but, similar tochordin(chd) morphants, resulted in mildly ventralized embryos by 24 hpf. Overall, our findings suggest that TDCIPP-induced epiboly delay may not be driven by decreasedszlexpression, and that TDCIPP-induced dorsalization may—similar to dorsomorphin—be due to interference with BMP signaling during early zebrafish development.
- Published
- 2017
- Full Text
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43. Mechanisms of selenomethionine developmental toxicity and the impacts of combined hypersaline conditions on Japanese medaka (Oryzias latipes)
- Author
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Daniel Schlenk and Allison Kupsco
- Subjects
Fish Proteins ,Salinity ,Embryo, Nonmammalian ,animal structures ,Oryzias ,Developmental toxicity ,Apoptosis ,medicine.disease_cause ,Article ,Toxicology ,Andrology ,chemistry.chemical_compound ,Toxicity Tests ,Genetics ,medicine ,Environmental Chemistry ,Animals ,Selenomethionine ,Nonmammalian ,biology ,ATF6 ,General Chemistry ,Japanese Medaka ,Glutathione ,biology.organism_classification ,6. Clean water ,Oxidative Stress ,chemistry ,Gene Expression Regulation ,Embryo ,Toxicity ,embryonic structures ,Unfolded protein response ,Unfolded Protein Response ,Generic health relevance ,Lipid Peroxidation ,Oxidative stress ,Environmental Sciences - Abstract
Selenium (Se) is an essential micronutrient that can cause embryotoxicty at levels 7-30 times above essential concentrations. Exposure to hypersaline conditions and 50 μM selenomethionine (SeMet) decreased embryo hatch and depleted glutathione in Japanese medaka embryos without affecting Se accumulation. To better understand the impacts of nonchemical stressors on developmental toxicity of Se in fish, several adverse outcome pathways were evaluated in the Japanese medaka (Oryzias latipes). We treated medaka embryos at 12 h post fertilization with 50 μM SeMet for 12 hours in freshwater or in 13 ppth hypersalinity and evaluated the contributions of oxidative stress, the unfolded protein response and apoptosis to reduced hatch. Exposure to SeMet and hypersalinity decreased embryo hatch to 3.7% ± 1.95, and induced teratogenesis in 100% ± 0 of hatched embryos. In contrast, treatments of freshwater, saltwater, and SeMet in freshwater resulted in 89.8% ± 3.91-86.7% ± 3.87 hatch, and no significant increase in deformities. We found no significant differences in lipid peroxidation, indicating that oxidative stress may not be responsible for the observed toxicity in embryos at this time point (24 h). Although significant changes in apoptosis were not observed, we witnessed up to 100 fold increases in transcripts of the endoplasmic reticulum (ER) chaperone, immunoglobulin binding protein (BiP) and trends toward increasing downstream signals, activating transcription factor 4 (ATF4) and ATF6 indicating potential contributions of the unfolded protein response to the effects of SeMet and hypersaline conditions. These data indicate that multiple adverse outcome pathways may be responsible for the developmental toxicity of Se and salinity, and these pathways may be time dependent.
- Published
- 2014
44. Developmental control of growth and cell cycle progression in Drosophila
- Author
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Lisa, Swanhart, Jeremy, Kupsco, and Robert J, Duronio
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Male ,Drosophila melanogaster ,Oogenesis ,Cell Cycle ,Animals ,Wings, Animal ,Apoptosis ,Female ,Eye ,Models, Biological ,Cell Division - Abstract
Drosophila melanogaster provides an outstanding experimental system to study the regulation of cell cycle progression during animal development. Sophisticated forward and reverse genetic techniques and the ability to observe detailed cell biological phenomena in vivo have allowed an unparalleled analysis of the cell cycle in the context of a whole animal. This chapter provides an overview of the diverse modes of cell cycle control that are utilized at different stages of Drosophila development.
- Published
- 2004
45. Developmental Control of Growth and Cell Cycle Progression in Drosophila
- Author
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Lisa M. Swanhart, Robert J. Duronio, and Jeremy M. Kupsco
- Subjects
medicine.anatomical_structure ,biology ,Cell cycle control ,Cell cycle progression ,Cell ,medicine ,Context (language use) ,Animal development ,Cell cycle ,Drosophila melanogaster ,biology.organism_classification ,Drosophila ,Cell biology - Abstract
Drosophila melanogaster provides an outstanding experimental system to study the regulation of cell cycle progression during animal development. Sophisticated forward and reverse genetic techniques and the ability to observe detailed cell biological phenomena in vivo have allowed an unparalleled analysis of the cell cycle in the context of a whole animal. This chapter provides an overview of the diverse modes of cell cycle control that are utilized at different stages of Drosophila development.
- Published
- 2004
- Full Text
- View/download PDF
46. stringcdc25 and cyclin E are required for patterned histone expression at different stages of Drosophila embryonic development
- Author
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Lanzotti, David, Duronio, Robert, Marzluff, William, and Kupsco, Jeremy
- Abstract
Metazoan replication-dependent histone mRNAs accumulate to high levels during S phase as a result of an increase in the rate of histone gene transcription, pre-mRNA processing, and mRNA stability at the G1–S transition. However, relatively little is known about the contribution of these processes to histone expression in the cell cycles of early development, which often lack a G1 phase. In post-blastoderm Drosophila embryos, zygotic expression of the stgcdc25 phosphatase in G2 activates cyclin/cdc2 kinases and triggers mitosis. Here we show that histone transcription initiates in late G2 of cycle 14 in response to stgcdc25 and in anticipation of S phase of the next cycle, which occurs immediately following mitosis. Mutation of stgcdc25 arrests cells in G2 and prevents histone transcription. Expression of a mutant form of Cdc2 that bypasses the requirement for stgcdc25 activates histone transcription during G2 in stgcdc25 mutant embryos. Thus, in these embryonic cycles, histone transcription is controlled by the principal G2–M regulators, stringcdc25, and cdc2 kinase, rather than solely by regulators of the G1–S transition. After the introduction of G1–S control midway through embryogenesis, histone expression depends on DNA replication and the function of cyclin E, and no longer requires stgcdc25. Thus, during the altered cell cycles of early animal development, different cell cycle mechanisms are employed to ensure that the production of histones accompanies DNA synthesis.
- Published
- 2004
- Full Text
- View/download PDF
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