Publications by authors named "Jill Franzosa"

Background: The number of chemicals present in the environment exceeds the capacity of government bodies to characterize risk. Therefore, data-informed and reproducible processes are needed for identifying chemicals for further assessment. The Minnesota Department of Health (MDH), under its Contaminants of Emerging Concern (CEC) initiative, uses a standardized process to screen potential drinking water contaminants based on toxicity and exposure potential.

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FutureTox IV, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in November 2018. Building upon FutureTox I, II, and III, this conference focused on the latest science and technology for in vitro profiling and in silico modeling as it relates to predictive developmental and reproductive toxicity (DART). Publicly available high-throughput screening data sets are now available for broad in vitro profiling of bioactivities across large inventories of chemicals.

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Article Synopsis
  • * Researchers examined differentiated HepaRG cells, which represent liver functions, measuring the expression of 93 gene transcripts in response to 1060 chemicals over multiple concentrations.
  • * Using a Bayesian framework, the study modeled how these chemicals affected gene expression through six key transcription factors, offering insights into the molecular signaling pathways relevant for toxicology in human liver cells.
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The more than 80,000 chemicals in commerce present a challenge for hazard assessments that toxicity testing in the 21 century strives to address through high-throughput screening (HTS) assays. Assessing chemical effects on human development adds an additional layer of complexity to the screening, with a need to capture complex and dynamic events essential for proper embryo-fetal development. HTS data from ToxCast/Tox21 informs systems toxicology models, which incorporate molecular targets and biological pathways into mechanistic models describing the effects of chemicals on human cells, 3D organotypic culture models, and small model organisms.

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Use of high-throughput, in vitro bioactivity data in setting a point-of-departure (POD) has the potential to accelerate the pace of human health safety evaluation by informing screening-level assessments. The primary objective of this work was to compare PODs based on high-throughput predictions of bioactivity, exposure predictions, and traditional hazard information for 448 chemicals. PODs derived from new approach methodologies (NAMs) were obtained for this comparison using the 50th (PODNAM, 50) and the 95th (PODNAM, 95) percentile credible interval estimates for the steady-state plasma concentration used in in vitro to in vivo extrapolation of administered equivalent doses.

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Cleft palate has been linked to both genetic and environmental factors that perturb key events during palatal morphogenesis. As a developmental outcome, it presents a challenging, mechanistically complex endpoint for predictive modeling. A data set of 500 chemicals evaluated for their ability to induce cleft palate in animal prenatal developmental studies was compiled from Toxicity Reference Database and the biomedical literature, which included 63 cleft palate active and 437 inactive chemicals.

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High throughput screening (HTS) programs have demonstrated that the Vitamin D receptor (VDR) is activated and/or antagonized by a wide range of structurally diverse chemicals. In this study, we examined the Tox21 qHTS data set generated against VDR for reproducibility and concordance and elucidated functional insights into VDR-xenobiotic interactions. Twenty-one potential VDR agonists and 19 VDR antagonists were identified from a subset of >400 compounds with putative VDR activity and examined for VDR functionality utilizing select orthogonal assays.

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Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay.

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Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High-throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay.

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Article Synopsis
  • Retinoic acid (RA) is crucial for the proper development of vertebrates, but its improper regulation can lead to developmental defects.
  • MicroRNAs (miRNAs), particularly the miR-19 family, play an important role in regulating metabolic enzymes like CYP26A1 that control RA levels during development.
  • Research showed that RA exposure reduces miR-19 levels, which in turn misregulates CYP26A1, leading to axis defects; restoring miR-19 levels can counteract these effects.
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Background: MicroRNAs (miRNAs) are noncoding RNAs that direct post-transcriptional regulation of protein coding genes. Recent studies have shown miRNAs are important for controlling many biological processes, including nervous system development, and are highly conserved across species. Given their importance, computational tools are necessary for analysis, interpretation and integration of high-throughput (HTP) miRNA data in an increasing number of model species.

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microRNAs (miRNAs) have emerged as regulators of a broad spectrum of neurodevelopmental processes, including brain morphogenesis, neuronal differentiation, and survival. While the role of miRNAs in establishing and maintaining the developing nervous system is widely appreciated, the developmental neurobehavioral role of miRNAs has yet to be defined. Here we show that transient disruption of brain morphogenesis by ethanol exposure results in behavioral hyperactivity in larval zebrafish challenged with changes in lighting conditions.

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Background: Pyrethrins are the insecticidally active components of pyrethrum extract, derived from flowers of Chrysanthemum cinerariifolium and used in commercial and consumer insecticide products. Most dermal testing performed with pyrethrum extracts was done before current refined pyrethrum concentrate became available (before 1967).

Objective: We analyzed presently commercially available pyrethrum allergen extracts to determine the concentration of pyrethrins and the putative sensitizer pyrethrosin.

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This short review provides a current synopsis of caudal fin regeneration in zebrafish with an emphasis on the molecular signaling networks that dictate epimorphic regeneration. At the outset, the fundamentals of caudal fin architecture and the stages of epimorphic regeneration are described. This is followed by a detailed look at the main networks implicated in fin regeneration, namely the Wnt, fibroblast growth factor, activin-betaA, retinoic acid and hedgehog signaling pathways.

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Zebrafish have the remarkable ability to regenerate body parts including the heart and fins by a process referred to as epimorphic regeneration. Recent studies have illustrated that similar to adult zebrafish, early life stage larvae also possess the ability to regenerate the caudal fin. A comparative microarray analysis was used to determine the degree of conservation in gene expression among the regenerating adult caudal fin, adult heart, and larval fin.

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Reports suggest that pyrethrum, the insecticidally active extract from Chrysanthemum cinerariifolium, can induce Type I hypersensitivity reactions in humans. Using knowledge of pyrethrum chemistry and an evidence-based analysis of literature, whether current refined pyrethrum induces and/or elicits skin manifestations of contact urticaria was assessed. Current extraction and refinement techniques suggest that refined pyrethrum lacks the presence of significant, if any, proteins speculated to induce Type I hypersensitivity.

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Pyrethrum has been reported to produce allergic contact dermatitis in humans. Moreover, it has been speculated that cross reactions occur in ragweed-sensitized people. This review presents the botany, contemporary chemistry, and case reports of alleged allergic contact dermatitis.

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Objective: We assessed the effect of 670-nm light therapy on growth and hatching kinetics in chickens (Gallus gallus) exposed to dioxin.

Background Data: Photobiomodulation has been shown to stimulate signaling pathways resulting in improved energy metabolism, antioxidant production, and cell survival. In ovo treatment with 670-nm light-emitting diode (LED) arrays improves hatching success and increases hatchling size in control chickens.

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Objective: We assessed the effect of 670-nm light therapy on dioxin-induced embryonic mortality in chickens (Gallus gallus).

Background Data: Developmental photobiomodulation using 670-nm light-emitting diode (LED) arrays improves hatching success and increases body size in hatchling chickens. Photobiomodulation also stimulates signaling pathways resulting in improved energy metabolism, antioxidant production and cell survival.

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Objective: The objective of the present study was to assess the survival and hatching success of chickens (Gallus gallus) exposed in ovo to far-red (670-nm) LED therapy.

Background Data: Photobiomodulation by light in the red to near-infrared range (630-1000 nm) using low-energy lasers or light-emitting diode (LED) arrays has been shown to accelerate wound healing and improve recovery from ischemic injury. The mechanism of photobiomodulation at the cellular level has been ascribed to the activation of mitochondrial respiratory chain components resulting in initiation of a signaling cascade that promotes cellular proliferation and cytoprotecton.

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