Abstract Graphene (Gr) nanomaterials are one of the fastest growing nanotechnology markets with a variety of applications in numerous industries due to a battery of unique physicochemical properties related to two-dimensional structure. Occupational exposure to graphenes by inhalation is a concern. Understanding the relationship of these properties to toxicity is critical for better predicting risk. The goal of this study was to associate material properties of this class of two-dimensional material with parameters of pulmonary toxicity and pathology. In vivo pulmonary exposure studies were previously conducted to compare different graphene nanomaterials [Gr that varied in lateral dimension, graphene oxide (GO), and reduced GO (rGO)] and carbon-based reference nanomaterials [carbon black (CB) and multi-walled carbon nanotubes (MWCNT)]. Size, density, surface area, oxygen content, as well as reactivity, agglomeration size, and zeta potential in delivery vehicle for oropharyngeal aspiration were measured. MWCNT and rGO caused persistent inflammation and a fibrotic response over time whereas inflammatory responses to other materials were transient. A classification Random Forest was used to predict toxicity grouping based on material properties to determine variable importance. Grouping was determined by significant difference from control using lavage and pathology outcomes and incidence. Toxicity ranking was MWCNT=rGO>>Gr5=Gr20=GO=CB≥Gr1. Variable of importance varied by time and toxicity parameter; however, density and mean agglomerate size were critical factors in the highly toxic materials whereas surface area was the most important factor in less toxic groups. This study contributes to understanding the structure-activity of this material class and read-across toxicity assessments of similar emerging materials.
Abstract Thermal spray coating (TSC) is a surface treatment process whereby feedstock material is sprayed onto surfaces under pressure where it solidifies and forms a solid coating. In metal TSC processes, large quantities of aerosols, including fine and ultrafine metal particles are generated. However, exposure assessment for TSC is lacking. The goal of this study was to construct a TSC aerosol generation system and to characterize the physicochemical properties of aerosols generated during coating processes. A computer-controlled, automated electric arc wire-TSC aerosol generator system was built in an enclosed room, where a rotary motor rotates a metal feedstock pipe in circular and up-and-down directions to allow even deposition of coating material on the pipe surface. The characteristics of aerosolized particles during spray coating using a stainless-steel wire (PMET 720) showed that: 1) respirable mass concentrations ranged from 142–218 mg/m3 (3 spray shots with each shot of 1-sec during 20-min sampling), 2) diameter of peak particle number concentrations was between 360 nm and 400 nm, 3) mass median aerodynamic diameter determined by an impactor ranged from 290–370 nm, 4) particle morphology was observed to be diverse including chain-like agglomerates and spherical and cylinder-like shapes, and 5) metal composition was 80% iron, 17% chromium, and 3% manganese with trace amounts of nickel and copper. These findings are limited to one wire type and suggests the need for further investigations evaluating various parameters (e.g., wire/powder types, high/low energy, ventilation on/off) to obtain emission rates and recommend control measures.
Female Aedes aegypti mosquitoes infect more than 400 million people each year with dangerous viral pathogens including dengue, yellow fever, Zika and chikungunya. Progress in understanding the biology of mosquitoes and developing the tools to fight them has been slowed by the lack of a high-quality genome assembly. Here we combine diverse technologies to produce the markedly improved, fully re-annotated AaegL5 genome assembly, and demonstrate how it accelerates mosquito science. We anchored physical and cytogenetic maps, doubled the number of known chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites, provided further insight into the size and composition of the sex-determining M locus, and revealed copy-number variation among glutathione S-transferase genes that are important for insecticide resistance. Using high-resolution quantitative trait locus and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly disease vector. ; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [U19AI110818]; USDA [2017-05741]; NIH Intramural Research Program; National Library of Medicine; National Human Genome Research Institute; NSF [PHY-1427654]; NIH [R01AI101112, R35GM118336, R21AI121853, R01AI123338, T32GM007739, NIH/NCATS UL1TR000043, DP2OD008540, U01AI088647, 1R01AI121211, D43TW001130-08, U01HL130010, UM1HG009375, 5K22AI113060, 1R21AI123937, R00DC012069]; Defence Advanced Research Project Agency [HR0011-17-2-0047]; Jane Coffin Childs Memorial Fund; Center for Theoretical Biological Physics postdoctoral fellowship; Robertson Foundation; McNair Foundation; Welch Foundation [Q-1866]; French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]; Agence Nationale de la Recherche [ANR-17-ERC2-0016-01]; European Union [734584]; Pew and Searle Scholars Programs; Klingenstein-Simons Fellowship in the Neurosciences; Verily Life Sciences ; We thank R. Andino; S. Emrich and D. Lawson (Vectorbase); A. A. James, M. Kunitomi, C. Nusbaum, D. Severson, N. Whiteman; T. Dickinson, M. Hartley and B. Rice (Dovetail Genomics) for early participation in the AGWG; C. Bargmann, D. Botstein, E. Jarvis and E. Lander for encouragement and facilitation. N. Keivanfar, D. Jaffe and D. M. Church (10X Genomics) prepared DNA for structural-variant analysis. We thank A. Harmon of the New York Times and acknowledge generous pro bono data and analysis from our corporate collaborators. This research was supported in part by federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under grant number U19AI110818 to the Broad Institute (S.N.R. and D.E.N.); USDA 2017-05741 (E.L.A.); NSF PHY-1427654 Center for Theoretical Biological Physics (E.L.A.); NIH Intramural Research Program, National Library of Medicine and National Human Genome Research Institute (A.M.P. and S.K.) and the following extramural NIH grants: R01AI101112 (J.R.P.), R35GM118336 (R.S.M. and W.J.G.), R21AI121853 (M.V.S., I.V.S. and A. S.), R01AI123338 (Z.T.), T32GM007739 (M.H.), NIH/NCATS UL1TR000043 (Rockefeller University), DP2OD008540 (E.L.A.), U01AI088647, 1R01AI121211 (W.C.B. IV), Fogarty Training Grant D43TW001130-08, U01HL130010 (E.L.A.), UM1HG009375 (E.L.A), 5K22AI113060 (O.S.A.), 1R21AI123937 (O.S.A.), and R00DC012069 (C.S.M.); Defence Advanced Research Project Agency: HR0011-17-2-0047 (O.S.A.). Other support was provided by Jane Coffin Childs Memorial Fund (B.J.M.), Center for Theoretical Biological Physics postdoctoral fellowship (O.D.), Robertson Foundation (L.Z.), and McNair & Welch (Q-1866) Foundations (E.L.A.), French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID to L.L.), Agence Nationale de la Recherche grant ANR-17-ERC2-0016-01 (L.L.), European Union's Horizon 2020 research and innovation program under ZikaPLAN grant agreement no. 734584 (L.L.), Pew and Searle Scholars Programs (C.S.M.), Klingenstein-Simons Fellowship in the Neurosciences (C.S.M.). A.M.W., B.J.W., J.E.C. and S.N.M. were supported by Verily Life Sciences. L.B.V. is an investigator of the Howard Hughes Medical Institute.
