Publications by authors named "Derek Green"

7 Publications

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A Novel Multispecies Toxicokinetic Modeling Approach in Support of Chemical Risk Assessment.

Environ Sci Technol 2021 07 24;55(13):9109-9118. Epub 2021 Jun 24.

Toxicology Centre, University of Saskatchewan, Saskatoon S7N 5B3, Canada.

Standardized laboratory tests with a limited number of model species are a key component of chemical risk assessments. These surrogate species cannot represent the entire diversity of native species, but there are practical and ethical objections against testing chemicals in a large variety of species. In previous research, we have developed a multispecies toxicokinetic model to extrapolate chemical bioconcentration across species by combining single-species physiologically based toxicokinetic (PBTK) models. This "top-down" approach was limited, however, by the availability of fully parameterized single-species models. Here, we present a "bottom-up" multispecies PBTK model based on available data from 69 freshwater fishes found in Canada. Monte Carlo-like simulations were performed using statistical distributions of model parameters derived from these data to predict steady-state bioconcentration factors (BCFs) for a set of well-studied chemicals. The distributions of predicted BCFs for 1,4-dichlorobenzene and dichlorodiphenyltrichloroethane largely overlapped those of empirical data, although a tendency existed toward overestimation of measured values. When expressed as means, predicted BCFs for 26 of 34 chemicals (82%) deviated by less than 10-fold from measured data, indicating an accuracy similar to that of previously published single-species models. This new model potentially enables more environmentally relevant predictions of bioconcentration in support of chemical risk assessments.
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http://dx.doi.org/10.1021/acs.est.1c02055DOI Listing
July 2021

Remodeling of Arctic char (Salvelinus alpinus) lipidome under a stimulated scenario of Arctic warming.

Glob Chang Biol 2021 07 2;27(14):3282-3298. Epub 2021 May 2.

Toxicology Centre, University of Saskatchewan, Saskatoon, SK, Canada.

Arctic warming associated with global climate change poses a significant threat to populations of wildlife in the Arctic. Since lipids play a vital role in adaptation of organisms to variations in temperature, high-resolution mass-spectrometry-based lipidomics can provide insights into adaptive responses of organisms to a warmer environment in the Arctic and help to illustrate potential novel roles of lipids in the process of thermal adaption. In this study, we studied an ecologically and economically important species-Arctic char (Salvelinus alpinus)-with a detailed multi-tissue analysis of the lipidome in response to chronic shifts in temperature using a validated lipidomics workflow. In addition, dynamic alterations in the hepatic lipidome during the time course of shifts in temperature were also characterized. Our results showed that early life stages of Arctic char were more susceptible to variations in temperature. One-year-old Arctic char responded to chronic increases in temperature with coordinated regulation of lipids, including headgroup-specific remodeling of acyl chains in glycerophospholipids (GP) and extensive alterations in composition of lipids in membranes, such as less lyso-GPs, and more ether-GPs and sphingomyelin. Glycerolipids (e.g., triacylglycerol, TG) also participated in adaptive responses of the lipidome of Arctic char. Eight-week-old Arctic char exhibited rapid adaptive alterations of the hepatic lipidome to stepwise decreases in temperature while showing blunted responses to gradual increases in temperature, implying an inability to adapt rapidly to warmer environments. Three common phosphatidylethanolamines (PEs) (PE 36:6|PE 16:1_20:5, PE 38:7|PE 16:1_22:6, and PE 40:7|PE 18:1_22:6) were finally identified as candidate lipid biomarkers for temperature shifts via machine learning approach. Overall, this work provides additional information to a better understanding of underlying regulatory mechanisms of the lipidome of Arctic organisms in the face of near-future warming.
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http://dx.doi.org/10.1111/gcb.15638DOI Listing
July 2021

Development of a Comprehensive Toxicity Pathway Model for 17α-Ethinylestradiol in Early Life Stage Fathead Minnows ().

Environ Sci Technol 2021 04 23;55(8):5024-5036. Epub 2021 Mar 23.

Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada.

There is increasing pressure to develop alternative ecotoxicological risk assessment approaches that do not rely on expensive, time-consuming, and ethically questionable live animal testing. This study aimed to develop a comprehensive early life stage toxicity pathway model for the exposure of fish to estrogenic chemicals that is rooted in mechanistic toxicology. Embryo-larval fathead minnows (FHM; ) were exposed to graded concentrations of 17α-ethinylestradiol (water control, 0.01% DMSO, 4, 20, and 100 ng/L) for 32 days. Fish were assessed for transcriptomic and proteomic responses at 4 days post-hatch (dph), and for histological and apical end points at 28 dph. Molecular analyses revealed core responses that were indicative of observed apical outcomes, including biological processes resulting in overproduction of vitellogenin and impairment of visual development. Histological observations indicated accumulation of proteinaceous fluid in liver and kidney tissues, energy depletion, and delayed or suppressed gonad development. Additionally, fish in the 100 ng/L treatment group were smaller than controls. Integration of omics data improved the interpretation of perturbations in early life stage FHM, providing evidence of conservation of toxicity pathways across levels of biological organization. Overall, the mechanism-based embryo-larval FHM model showed promise as a replacement for standard adult live animal tests.
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http://dx.doi.org/10.1021/acs.est.0c05942DOI Listing
April 2021

In ovo exposure of fathead minnow (Pimephales promelas) to selenomethionine via maternal transfer and embryo microinjection: A comparative study.

Aquat Toxicol 2019 Nov 16;216:105299. Epub 2019 Sep 16.

Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5B3, Canada; School of Environment and Sustainability, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5C8, Canada. Electronic address:

Selenium (Se) is an essential trace element of concern that is known to contaminate aquatic ecosystems as a consequence of releases from anthropogenic activities. Selenium is of particular toxicological concern for egg-laying vertebrates as they bioaccumulate Se through the diet and deposit excess Se to embryo-offspring via maternal transfer, a process which has been shown to result in significant teratogenic effects. The purpose of the present study was to determine and compare the in ovo effects of Se exposure on early development of a laboratory model fish species native to North American freshwater systems, the fathead minnow (Pimephales promelas), through two different exposure routes, maternal transfer and microinjection. For maternal transfer studies, fathead minnow breeding groups (3 females: 2 males) were exposed to diets containing Se-background levels (1.21 μg Se/g food, dry mass [dm]) or environmentally relevant concentrations of selenomethionine (SeMet; 3.88, 8.75 and 26.5 μg Se/g food dm) and bred for 28 days. Embryos were collected at different time points throughout the study to measure Se concentrations and to assess teratogenicity in embryos. While exposure to dietary Se did not negatively affect fecundity among treatment groups, the lowest treatment group (3.88 μg Se/g food dm) produced on average the most embryos per day, per female. The maternal transfer of excess Se occurred rapidly upon onset of exposure, reaching steady-state after approximately 14 days, and embryo Se concentrations increased in a dose-dependent manner. The greatest concentrations of maternally transferred Se significantly increased the total proportion of deformed embryo-larval fathead minnows but did not impact hatchability or survival. In a second study, fathead minnow embryos were injected with SeMet at concentrations of 0.00 (vehicle control), 9.73, 13.5 and 18.9 μg Se/g embryo dm. Microinjection of SeMet did not affect hatchability but significantly increased the proportion of deformed embryo-larval fish in a dose-dependent manner. There was a greater proportion of deformed fathead minnows at embryo Se concentrations of 18.9 μg Se/g embryo dm when exposed via microinjection versus maternal transfer at concentrations of 28.4 μg Se/g embryo dm. However, the findings suggest that both exposure routes induced analogous developmental toxicities in early life stage fish at Se concentrations between 9.73 and 13.5 μg Se/g embryo dm. Overall, this study demonstrated that microinjection has utility for studying the effects of Se in embryo-larval fish and is a promising method for the study of early life stage Se exposure in egg-laying vertebrates.
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http://dx.doi.org/10.1016/j.aquatox.2019.105299DOI Listing
November 2019

Plant cell wall glycosyltransferases: High-throughput recombinant expression screening and general requirements for these challenging enzymes.

PLoS One 2017 9;12(6):e0177591. Epub 2017 Jun 9.

Joint BioEnergy Institute, Emeryville, California, United States of America.

Molecular characterization of plant cell wall glycosyltransferases is a critical step towards understanding the biosynthesis of the complex plant cell wall, and ultimately for efficient engineering of biofuel and agricultural crops. The majority of these enzymes have proven very difficult to obtain in the needed amount and purity for such molecular studies, and recombinant cell wall glycosyltransferase production efforts have largely failed. A daunting number of strategies can be employed to overcome this challenge, including optimization of DNA and protein sequences, choice of expression organism, expression conditions, co-expression partners, purification methods, and optimization of protein solubility and stability. Hence researchers are presented with thousands of potential conditions to test. Ultimately, the subset of conditions that will be sampled depends on practical considerations and prior knowledge of the enzyme(s) being studied. We have developed a rational approach to this process. We devise a pipeline comprising in silico selection of targets and construct design, and high-throughput expression screening, target enrichment, and hit identification. We have applied this pipeline to a test set of Arabidopsis thaliana cell wall glycosyltransferases known to be challenging to obtain in soluble form, as well as to a library of cell wall glycosyltransferases from other plants including agricultural and biofuel crops. The screening results suggest that recombinant cell wall glycosyltransferases in general have a very low soluble:insoluble ratio in lysates from heterologous expression cultures, and that co-expression of chaperones as well as lysis buffer optimization can increase this ratio. We have applied the identified preferred conditions to Reversibly Glycosylated Polypeptide 1 from Arabidopsis thaliana, and processed this enzyme to near-purity in unprecedented milligram amounts. The obtained preparation of Reversibly Glycosylated Polypeptide 1 has the expected arabinopyranose mutase and autoglycosylation activities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177591PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466300PMC
September 2017

Historical and Contemporary Patterns of Mercury in a Hydroelectric Reservoir and Downstream Fishery: Concentration Decline in Water and Fishes.

Arch Environ Contam Toxicol 2016 Aug 6;71(2):157-70. Epub 2016 Jun 6.

Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, S7N 5B3, Canada.

Mercury (Hg) contamination can pose risks to human and animal health as well as commercial fisheries. Reservoir construction in riverine systems produces flooded conditions amenable to Hg(II)-methylating bacteria, which can transform this relatively benign environmental contaminant into the bioaccumulative, environmentally relevant, and neurotoxic methyl-Hg (MeHg). Hg concentrations ([Hg]) in fishes from reservoirs can take decades to decrease to pre-dam levels, but less is known about Hg exported downstream and its dynamics within downstream fish populations. We examined and compared the multidecadal rates of biotic [Hg] decrease and contemporary factors affecting [Hg] in fish collected from a hydroelectric reservoir (Tobin Lake) and a related downstream fishery (Cumberland Lake) along the Saskatchewan River, Canada. Rates of [Hg] decrease were considered in four species-northern pike (Esox lucius), sauger (Sander canadensis), goldeye (Hiodon alosoides), and walleye (S. vitreus)-all of which showed a significant decrease over time (p < 0.001) and are now lower than Health Canada consumption guidelines (0.5 μg/g). Rates of decrease ranged from 0.5 to 3.9 %/year and were similar between sites in the cases of northern pike and sauger. Contemporary factors affecting [Hg] in walleye collected downstream include fish length (p < 0.001), fish age (p < 0.001), and trophic magnification through the food web (p < 0.001), and relationships between [Hg] and trophic level in predatory and prey fish are now similar to those found in non-Hg-inundated systems at a similar latitude. Together, these results suggest connected contamination between the two sites and delineate the timeline during which [Hg] in a variety of fish species decreased to nontoxic levels in both locations.
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http://dx.doi.org/10.1007/s00244-016-0287-3DOI Listing
August 2016

African American community leaders' policy recommendations for reducing racial disparities in HIV infection, treatment, and care: results from a community-based participatory research project in Philadelphia, Pennsylvania.

Health Promot Pract 2015 Jan 30;16(1):91-100. Epub 2014 May 30.

Philadelphia City Council, Philadelphia, PA, USA.

African Americans account for 45% of new HIV infections in the United States. Little empirical research investigates African American community leaders' normative recommendations for addressing these disparities. Philadelphia's HIV infection rate is 5 times the national average, nearly 70% of new infections are among African Americans, and 2% of African Americans in Philadelphia are living with HIV/AIDS. Using a community-based participatory research approach, we convened focus groups among 52 African American community leaders from diverse backgrounds to solicit normative recommendations for reducing Philadelphia's racial disparities in HIV infection. Leaders recommended that (a) Philadelphia's city government should raise awareness about HIV/AIDS with media campaigns featuring local leaders, (b) local HIV-prevention interventions should address social and structural factors influencing HIV risks rather than focus exclusively on mode of HIV transmission, (c) resources should be distributed to the most heavily affected neighborhoods of Philadelphia, and (d) faith institutions should play a critical role in HIV testing, treatment, and prevention efforts. We developed a policy memo highlighting these normative recommendations for how to enhance local HIV prevention policy. This policy memo led to Philadelphia City Council hearings about HIV/AIDS in October 2010 and subsequently informed local HIV/AIDS prevention policy and development of local HIV prevention interventions. This community-based participatory research case study offers important lessons for effectively engaging community leaders in research to promote HIV/AIDS policy change.
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http://dx.doi.org/10.1177/1524839914534855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639925PMC
January 2015
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