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

Dynamic Zebrafish Interactome Reveals Transcriptional Mechanisms of Dioxin Toxicity

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.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.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

Smaller classes promote equitable student participation in STEM

Under embargo until: 2020-07-24As science, technology, engineering, and mathematics (STEM) classrooms in higher education transition from lecturing to active learning, the frequency of student interactions in class increases. Previous research documents a gender bias in participation, with women participating less than would be expected on the basis of their numeric proportions. In the present study, we asked which attributes of the learning environment contribute to decreased female participation: the abundance of in-class interactions, the diversity of interactions, the proportion of women in class, the instructor's gender, the class size, and whether the course targeted lower division (first and second year) or upper division (third or fourth year) students. We calculated likelihood ratios of female participation from over 5300 student–instructor interactions observed across multiple institutions. We falsified several alternative hypotheses and demonstrate that increasing class size has the largest negative effect. We also found that when the instructors used a diverse range of teaching strategies, the women were more likely to participate after small-group discussions.acceptedVersio

Synergistic Embryotoxicity of Polycyclic Aromatic Hydrocarbon Aryl Hydrocarbon Receptor Agonists with Cytochrome P4501A Inhibitors in -2

<p><b>Copyright information:</b></p><p>Taken from "Synergistic Embryotoxicity of Polycyclic Aromatic Hydrocarbon Aryl Hydrocarbon Receptor Agonists with Cytochrome P4501A Inhibitors in "</p><p>Environmental Health Perspectives 2004;112(17):1658-1664.</p><p>Published online 18 Aug 2004</p><p>PMCID:PMC1253655.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Synergistic Embryotoxicity of Polycyclic Aromatic Hydrocarbon Aryl Hydrocarbon Receptor Agonists with Cytochrome P4501A Inhibitors in -5

<p><b>Copyright information:</b></p><p>Taken from "Synergistic Embryotoxicity of Polycyclic Aromatic Hydrocarbon Aryl Hydrocarbon Receptor Agonists with Cytochrome P4501A Inhibitors in "</p><p>Environmental Health Perspectives 2004;112(17):1658-1664.</p><p>Published online 18 Aug 2004</p><p>PMCID:PMC1253655.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Synergistic Embryotoxicity of Polycyclic Aromatic Hydrocarbon Aryl Hydrocarbon Receptor Agonists with Cytochrome P4501A Inhibitors in -0

<p><b>Copyright information:</b></p><p>Taken from "Synergistic Embryotoxicity of Polycyclic Aromatic Hydrocarbon Aryl Hydrocarbon Receptor Agonists with Cytochrome P4501A Inhibitors in "</p><p>Environmental Health Perspectives 2004;112(17):1658-1664.</p><p>Published online 18 Aug 2004</p><p>PMCID:PMC1253655.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Synergistic Embryotoxicity of Polycyclic Aromatic Hydrocarbon Aryl Hydrocarbon Receptor Agonists with Cytochrome P4501A Inhibitors in -1

<p><b>Copyright information:</b></p><p>Taken from "Synergistic Embryotoxicity of Polycyclic Aromatic Hydrocarbon Aryl Hydrocarbon Receptor Agonists with Cytochrome P4501A Inhibitors in "</p><p>Environmental Health Perspectives 2004;112(17):1658-1664.</p><p>Published online 18 Aug 2004</p><p>PMCID:PMC1253655.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p