Implications of Lead (Pb)-Induced Transcriptomic and Phenotypic Alterations in the Aged Zebrafish (Danio rerio) DOI Creative Commons
Chia‐Chen Wu,

Danielle Meyer,

Alex Haimbaugh

и другие.

Toxics, Год журнала: 2024, Номер 12(10), С. 745 - 745

Опубликована: Окт. 14, 2024

Lead (Pb) is a well-known neurotoxin with established adverse effects on the neurological functions of children and younger adults, including motor, learning, memory abilities. However, its potential impact older adults has received less attention. Using zebrafish model, our study aims to characterize dose-response relationship between environmentally relevant Pb exposure levels their changes in behavior transcriptomics during geriatric periods. We exposed two-year-old waterborne lead acetate (1, 10, 100, 1000, or 10,000 µg/L) vehicle (DMSO) for 5 days. While lower concentrations (1-100 reflect levels, higher (1000-10,000 were included assess acute toxicity under extreme scenarios. conducted adult assessment evaluate locomotor activity following exposure. The same individual fish subsequently sacrificed brain dissection after day recovery aquatic system. RNA extraction sequencing then performed Pb-induced transcriptomic changes. Higher ug/L) induced hyperactive patterns aged zebrafish, while (10-100 resulted lowest compared control group. Exposure 100 µg/L led highest number differentially expressed genes (DEGs), larger fold both directions. pathways impacted by include related neurotransmission, such as cytoskeletal regulation synaptogenesis, oxidative stress response, mitochondrial dysfunction downregulation heat shock protein genes. These findings emphasize U-shape aging brain.

Язык: Английский

Fish models to explore epigenetic determinants of hypoxia-tolerance DOI Creative Commons

William Johnston,

Sally Adil,

Catherine Cao

и другие.

Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology, Год журнала: 2025, Номер 302, С. 111811 - 111811

Опубликована: Янв. 6, 2025

Язык: Английский

Процитировано

1
Integration of multi-omics and benchmark dose modeling to support adverse outcome pathways DOI Creative Commons

Ngoc Q. Vuong,

Saadia Khilji,

A. Williams

и другие.

International Journal of Radiation Biology, Год журнала: 2025, Номер unknown, С. 1 - 14

Опубликована: Янв. 2, 2025

Background Recent advancements in omics and benchmark dose (BMD) modeling have facilitated identifying the required for a predetermined change response (e.g. gene or protein change) that can be used to establish acceptable levels hazardous exposures. Adverse Outcome Pathways (AOPs) describe causal links between toxicants adverse effects through key events (KEs). Integrating data within AOP framework quantitatively early molecular later phenotypic effects. In this study, we use omic-based BMD analyses an vitro blood model exposed radiation identify point of departure (POD) values across KEs acute myeloid leukemia (www.aopwiki.org/aop/432).

Язык: Английский

Процитировано

0
Gene Set Enrichment Analysis in Zebrafish Embryos Is Susceptible to False-Positive Results in the Absence of Differentially Expressed Genes DOI Creative Commons
John D. H. Stead, Hyojin Lee, Andrew Williams

и другие.

Bioinformatics and Biology Insights, Год журнала: 2025, Номер 19

Опубликована: Янв. 1, 2025

High-throughput gene expression studies commonly employ pathway analyses to infer biological meaning from lists of differentially expressed genes (DEGs). In toxicology and pharmacology studies, treatment groups are analysed against vehicle controls identify DEGs altered pathways. Previously, we empirically quantified false-positive rates in data pools vehicle-treated zebrafish embryos determine appropriate study designs (sample pool size). Here, the same were subject Over-Representation Analysis (ORA) Gene Set Enrichment (GSEA) enriched As expected, number ORA results was lowest where sample sizes largest (conditions which also generated fewest significant DEGs). contrast, frequency GSEA false-positives through fast (fgsea) algorithm increased with size highest for simulations that 0 DEGs, ribosomal sets significantly frequency. We describe 2 distinct mechanisms by these results, both most likely generate under conditions differences particularly low. Finally, repeated using 1 alternative (CERNO) 11 different ranking statistics. almost every analysis, highest, ribosome as more frequently set, suggesting our observations be generalizable implementations GSEA. These suggest caution interpreting any contrasts there no DEGs.

Язык: Английский

Процитировано

0
Implications of Lead (Pb)-Induced Transcriptomic and Phenotypic Alterations in the Aged Zebrafish (Danio rerio) DOI Creative Commons
Chia‐Chen Wu,

Danielle Meyer,

Alex Haimbaugh

и другие.

Toxics, Год журнала: 2024, Номер 12(10), С. 745 - 745

Опубликована: Окт. 14, 2024

Lead (Pb) is a well-known neurotoxin with established adverse effects on the neurological functions of children and younger adults, including motor, learning, memory abilities. However, its potential impact older adults has received less attention. Using zebrafish model, our study aims to characterize dose-response relationship between environmentally relevant Pb exposure levels their changes in behavior transcriptomics during geriatric periods. We exposed two-year-old waterborne lead acetate (1, 10, 100, 1000, or 10,000 µg/L) vehicle (DMSO) for 5 days. While lower concentrations (1-100 reflect levels, higher (1000-10,000 were included assess acute toxicity under extreme scenarios. conducted adult assessment evaluate locomotor activity following exposure. The same individual fish subsequently sacrificed brain dissection after day recovery aquatic system. RNA extraction sequencing then performed Pb-induced transcriptomic changes. Higher ug/L) induced hyperactive patterns aged zebrafish, while (10-100 resulted lowest compared control group. Exposure 100 µg/L led highest number differentially expressed genes (DEGs), larger fold both directions. pathways impacted by include related neurotransmission, such as cytoskeletal regulation synaptogenesis, oxidative stress response, mitochondrial dysfunction downregulation heat shock protein genes. These findings emphasize U-shape aging brain.

Язык: Английский

Процитировано

0