Publications by authors named "Preethi Thunga"

Zebrafish have become an essential model organism in screening for developmental neurotoxic chemicals and their molecular targets. The success of zebrafish as a screening model is partially due to their physical characteristics including their relatively simple nervous system, rapid development, experimental tractability, and genetic diversity combined with technical advantages that allow for the generation of large amounts of high-dimensional behavioral data. These data are complex and require advanced machine learning and statistical techniques to comprehensively analyze and capture spatiotemporal responses.

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Per- and polyfluoroalkyl substances (PFAS) are a widespread and persistent class of contaminants posing significant environmental and human health concerns. Comprehensive understanding of the modes of action underlying toxicity among structurally diverse PFAS is mostly lacking. To address this need, we recently reported on our application of developing zebrafish to evaluate a large library of PFAS for developmental toxicity.

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Article Synopsis
  • Zebrafish are increasingly valuable for identifying harmful chemicals and their effects on development due to their simple nervous systems and rapid growth.
  • Researchers have employed advanced semi-supervised deep learning techniques to analyze complex behavioral data from zebrafish, focusing on establishing a baseline of "normal" behavior.
  • The model identified new chemicals that cause abnormal behavior, enhancing our understanding of how different substances impact zebrafish and potentially informing studies on similar effects in more complex organisms.
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β-N-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria, which has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). It is postulated that chronic exposure to BMAA can lead to formation of protein aggregates, oxidative stress, and/or excitotoxicity, which are mechanisms involved in the etiology of ALS. While specific genetic mutations are identified in some instances of ALS, it is likely that a combination of genetic and environmental factors, such as exposure to the neurotoxin BMAA, contributes to disease.

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  • * A study using high-throughput zebrafish screening assessed how larval behavior and gene expression varied in response to PFHxA exposure, revealing significant GxE effects in behavior.
  • * Findings indicated that genetics directly influence both gene expression and behavioral responses to PFHxA, demonstrating the potential to utilize genetic variation in populations for GxE testing.
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  • Zebrafish have shown promise as a model for studying these interactions, and this study used bioinformatics and experimental methods to explore chemical susceptibility in a genetically diverse zebrafish population.
  • The research identified two distinct alleles associated with different susceptibility levels to the chemical Abamectin, revealing that the GG allele had higher expression levels than the TT allele, which correlated with differences in transcription factor binding.
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  • * Researchers found that the gene wfikkn1 is closely related to AHR activation in zebrafish and demonstrated that its expression depends on the Ahr2 gene in the presence of TCDD.
  • * Although wfikkn1 was shown to influence gene and protein expression related to muscle and neurological development after TCDD exposure, it did not significantly affect the toxicity of TCDD or alter behavior in mutant zebrafish, suggesting it plays a supportive role in AHR signaling rather than being a main driver of toxicity. *
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The continual introduction of new chemicals into the market necessitates fast, efficient testing strategies for evaluating their toxicity. Ideally, these high-throughput screening (HTS) methods should capture the entirety of biological complexity while minimizing reliance on expensive resources that are required to assess diverse phenotypic endpoints. In recent years, the zebrafish () has become a preferred vertebrate model to conduct rapid toxicity tests.

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Per- and polyfluoroalkyl substances (PFAS) are a class of widely used chemicals with limited human health effects data relative to the diversity of structures manufactured. To help fill this data gap, an extensive in vivo developmental toxicity screen was performed on 139 PFAS provided by the US EPA. Dechorionated embryonic zebrafish were exposed to 10 nominal water concentrations of PFAS (0.

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