Deena Wassenberg

Synergistic embryotoxicity of polycyclic aromatic hydrocarbon aryl hydrocarbon receptor agonists with cytochrome P4501A inhibitors in Fundulus heteroclitus.

Widespread contamination of aquatic systems with polycyclic aromatic hydrocarbons (PAHs) has led to concern about effects of PAHs on aquatic life. Some PAHs have been shown to cause deformities in early life stages of fish that resemble those elicited by planar halogenated aromatic hydrocarbons (pHAHs) that are agonists for the aryl hydrocarbon receptor (AHR). Previous studies have suggested that activity of cytochrome P4501A, a member of the AHR gene battery, is important to the toxicity of pHAHs, and inhibition of CYP1A can reduce the early-life-stage toxicity of pHAHs. In light of the effects of CYP1A inhibition on pHAH-derived toxicity, we explored the impact of both model and environmentally relevant CYP1A inhibitors on PAH-derived embryotoxicity. We exposed Fundulus heteroclitus embryos to two PAH-type AHR agonists, β-naphthoflavone and benzo(a)pyrene, and one pHAH-type AHR agonist, 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126), alone and in combination with several CYP1A inhibitors. In agreement with previous studies, coexposure of embryos to PCB-126 with the AHR antagonist and CYP1A inhibitor α-naphthoflavone decreased frequency and severity of deformities compared with embryos exposed to PCB-126 alone. In contrast, embryos coexposed to the PAHs with each of the CYP1A inhibitors tested were deformed with increased severity and frequency compared with embryos dosed with PAH alone. The mechanism by which inhibition of CYP1A increased embryotoxicity of the PAHs tested is not understood, but these results may be helpful in elucidating mechanisms by which PAHs are embryotoxic. Additionally, these results call into question additive models of PAH embryotoxicity for environmental PAH mixtures that contain both AHR agonists and CYP1A inhibitors.

Effects of the polycyclic aromatic hydrocarbon heterocycles, carbazole and dibenzothiophene, on in vivo and in vitro cyp1a activity and polycyclic aromatic hydrocarbon-derived embryonic deformities

Heterocyclic derivatives of polycyclic aromatic hydrocarbons (PAHs) are often significant components of environmental contaminant mixtures; however, their contribution to the toxicity of these mixtures is not well characterized. These heterocycles commonly co-occur in PAH mixtures, which contain agonists for the aryl hydrocarbon receptor (AHR). Our goal for these studies was to explore the effects of two PAH heterocycles, carbazole (CB) and dibenzothiophene (DBT), alone and in combination with a PAH-type agonist for the AHR (beta-naphthoflavone [BNF]) on AHR-mediated cytochrome P4501A (CYP1A) activity and on fish embryotoxicity. Embryos of Fundulus heteroclitus were exposed to CB or DBT, with and without coexposure to BNE Carbazole alone slightly induced, whereas DBT alone slightly reduced, in ovo CYP1A-mediated ethoxyresorufin-O-deethylase (EROD) activity compared to control values. However, exposure to CB or DBT reduced in ovo EROD activity in embryos coexposed to BNE Carbazole and DBT were characterized in vitro as noncompetitive CYP1A inhibitors. Carbazole and DBT enhanced the embryotoxicity of BNF, although neither compound was embryotoxic by itself. The co-occurrence of CB and DBT with PAH-type AHR inducers in contaminated ecosystems may increase the toxicity of PAH-type AHR agonists in these settings and may need to be considered when estimating the embryotoxicity of PAH mixtures.

Expression and inducibility of aryl hydrocarbon receptor pathway genes in wild-caught Killifish (Fundulus heteroclitus) with different contaminant-exposure histories

Wildcaught killifish from a contaminated site on the Elizabeth River (VA, USA) are refractory to induction of cytochrome P4501A (CYP1A, measured as catalytic activity and immunodetectable CYP1A protein) after exposure to typical aryl hydrocarbon receptor (AHR) agonists, as has been reported for fish from other sites highly contaminated with these compounds. In an attempt to understand the molecular basis for the lack of inducibility of CYP1A protein expression and activity in Elizabeth River killifish, we analyzed the expression of CYP1A and four other members of the AHR signal transduction pathway: AHR1, AHR2, AHR repressor (AHRR), and AHR nuclear translocator (ARNT). Gene expression was measured by cycle-optimized reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of messenger ribonucleic acid (mRNA) extracted from livers of killifish from the Elizabeth River and Kings Creek (VA, USA) (reference site), 36 h after injection with beta-naphthoflavone (BNF, an AHR agonist) or corn oil (carrier control). Hepatic CYP1A mRNA was inducible in Kings Creek killifish. However, in Elizabeth River killifish, no induction of CYP1A mRNA was observed, confirming and extending previous results showing no induction of CYP1A protein or catalytic activity in this population. Similarly, AHRR and AHR2 mRNA levels were induced by BNF in Kings Creek but not Elizabeth River killifish. No population or treatment-related differences were observed in expression of AHR1 or ARNT mRNAs. The results reveal in Elizabeth River killifish a consistent lack of inducibility of genes that are normally inducible by AHR agonists (CYP1A, AHRR, AHR2). However, the expression of AHR1, AHR2, and AHRR in vehicle-treated fish did not differ between Elizabeth River and Kings Creek killifish, suggesting that altered constitutive expression of AHRs or AHRR does not underlie the refractory CYP1A phenotype in Elizabeth River killifish.

Dynamic Zebrafish Interactome Reveals Transcriptional Mechanisms of Dioxin Toxicity

Background In order to generate hypotheses regarding the mechanisms by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) causes toxicity, we analyzed global gene expression changes in developing zebrafish embryos exposed to this potent toxicant in the context of a dynamic gene network. For this purpose, we also computationally inferred a zebrafish (Danio rerio) interactome based on orthologs and interaction data from other eukaryotes. Methodology/Principal Findings Using novel computational tools to analyze this interactome, we distinguished between dioxin-dependent and dioxin-independent interactions between proteins, and tracked the temporal propagation of dioxin-dependent transcriptional changes from a few genes that were altered initially, to large groups of biologically coherent genes at later times. The most notable processes altered at later developmental stages were calcium and iron metabolism, embryonic morphogenesis including neuronal and retinal development, a variety of mitochondria-related functions, and generalized stress response (not including induction of antioxidant genes). Within the interactome, many of these responses were connected to cytochrome P4501A (cyp1a) as well as other genes that were dioxin-regulated one day after exposure. This suggests that cyp1a may play a key role initiating the toxic dysregulation of those processes, rather than serving simply as a passive marker of dioxin exposure, as suggested by earlier research. Conclusions/Significance Thus, a powerful microarray experiment coupled with a flexible interactome and multi-pronged interactome tools (which are now made publicly available for microarray analysis and related work) suggest the hypothesis that dioxin, best known in fish as a potent cardioteratogen, has many other targets. Many of these types of toxicity have been observed in mammalian species and are potentially caused by alterations to cyp1a.

Considering the Role of “Need for Cognition” in Students' Acceptance of Climate Change & Evolution

Abstract Anthropogenic climate change (ACC) and evolution are examples of issues that are perceived differently by scientists and the general public. Within the scientific community, there are clear consensuses that human activities are increasing global temperatures (ACC) and that evolutionary mechanisms have led to the biodiversity of life on Earth (evolution). However, there is much debate in the public discourse about the scientific evidence supporting these topics. The purpose of our study was to explore the relationship between a students need for cognition (NFC) — preference to engage in and enjoy thinking — and the students acceptance of ACC and evolution. The results revealed that students with a higher NFC were more accepting of both ACC and evolution. Future investigations should include evaluating the efficacy of different instructional techniques on NFC and acceptance of polarizing topics such as evolution and ACC.

Do Small Classes in Higher Education Reduce Performance Gaps in STEM

Performance gaps in science are well documented, and an examination of underlying mechanisms that lead to underperformance and attrition of women and underrepresented minorities (URM) may offer highly targeted means to promote such students. Determining factors that influence academic performance may provide a basis for improved pedagogy and policy development at the university level. We examined the impact of class size on students in 17 biology courses at four universities. Although the female students underperformed on high-stakes exams compared with the men as class size increased, the women received higher scores than the men on nonexam assessments. The URM students underperformed across grade measures compared with the majority students regardless of class size, suggesting that other characteristics of the education environment affect learning. Student enrollment is expected to increase precipitously in the next decade, underscoring the need to prioritize individual student potential rather than yield to budget constraints when considering equitable pedagogy and caps on classroom sizes.