Project description:Domoic acid (DA) is a neuroexcitatory amino acid that is naturally produced by some marine diatom species of the genus Pseudo-nitzschia. Ingestion of DA-contaminated seafood by humans results in a severe neurotoxic disease known as amnesic shellfish poisoning (ASP). Clinical signs of ASP include seizures and neuronal damage from activation of AMPA and kainate receptors. However, the impacts of DA exposure at levels below those known to induce outward signs of neurobehavioral exicitotoxicity have not been well characterized. To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. Transcriptional profiles were suggestive of neuronal apoptosis following an overwhelming of protective adaptive pathways. Further, potential molecular biomarkers of neuropathic injury, including Nrdg4, were identified and may be relevant to DA exposure levels below that causing neurobehavioral injury. Our results validate zebrafish as a vertebrate model to study mechanisms of DA neurotoxicity and provide a basis for identifying pathways of DA-induced injury as well as biomarkers of asymptomatic and symptomatic DA exposure levels. Keywords: neurotoxic disease To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. All animal studies were carried out under approved IACUC protocols at the University of Washington.

Project description:Transcriptomic profiling of normal mouse thyroid tissue following 211At irradiation Introduction The cellular response to stimuli can be studied on different molecular levels, including gene expression regulation. RNA microarray is a high-throughput technique that enables comparison of genome-wide transcriptional status between samples. 211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. Metabolically released 211At accumulates in the thyroid gland, which is one of the main critical organs for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on transcriptional expression in mouse thyroid gland. Method BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean absorbed doses to thyroid of 0.023, 0.32, and 1.4 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively, resulting in mean absorbed doses to thyroid of 1.4 Gy. Animals were killed through cardiac puncture under anesthesia, and thyroids were removed and snap-frozen. Total RNA was extracted from pooled thyroid tissue samples and mRNA levels were determined with the Illumina RNA microarray platform. Nexus Expression 3.0 was used to identify differentially expressed transcripts (adjusted p-value <0.01, fold change >1.5) and enriched GO terms (p-value <0.05) between irradiated groups and controls. Results In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose when the exposure time was 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. This suggests that initial dose-rate (thus injected activity) is an important parameter in radiation-induced responses. Furthermore, the regulation profiles of groups administered 1.7 kBq were similar. Few previously proposed radiation responsive genes were identified in the present study, but, e.g. Gadd45g and Cdkn1a were among the regulated genes identified in the present study. A response involving immunological processes was identified especially at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy). Conclusion The present study allowed a comprehensive assessment of how variations in exposure parameters affect transcriptional regulation. The regulation profiles were dependent on both absorbed dose and time after exposure, but, initial dose-rate was the most influential parameter. Functional annotation of regulated genes revealed exposure-specific effects on biological processes. Additionally, we have identified several recurrently regulated genes after 211At exposure that may play a role in how mouse thyroid tissue responds to 211At exposure. Introduction The cellular response to stimuli can be studied on different molecular levels, including gene expression regulation. RNA microarray is a high-throughput technique that enables comparison of genome-wide transcriptional status between samples. 211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. Metabolically released 211At accumulates in the thyroid gland, which is one of the main critical organs for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on transcriptional expression in mouse thyroid gland. Method BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean absorbed doses to thyroid of 0.023, 0.32, and 1.4 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively, resulting in mean absorbed doses to thyroid of 1.4 Gy. Animals were killed through cardiac puncture under anesthesia, and thyroids were removed and snap-frozen. Total RNA was extracted from pooled thyroid tissue samples and mRNA levels were determined with the Illumina RNA microarray platform. Nexus Expression 3.0 was used to identify differentially expressed transcripts (adjusted p-value <0.01, fold change >1.5) and enriched GO terms (p-value <0.05) between irradiated groups and controls. Results In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose when the exposure time was 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. This suggests that initial dose-rate (thus injected activity) is an important parameter in radiation-induced responses. Furthermore, the regulation profiles of groups administered 1.7 kBq were similar. Few previously proposed radiation responsive genes were identified in the present study, but, e.g. Gadd45g and Cdkn1a were among the regulated genes identified in the present study. A response involving immunological processes was identified especially at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy). Conclusion The present study allowed a comprehensive assessment of how variations in exposure parameters affect transcriptional regulation. The regulation profiles were dependent on both absorbed dose and time after exposure, but, initial dose-rate was the most influential parameter. Functional annotation of regulated genes revealed exposure-specific effects on biological processes. Additionally, we have identified several recurrently regulated genes after 211At exposure that may play a role in how mouse thyroid tissue responds to 211At exposure. Total RNA was isolated from fresh-frozen tissue samples (Normal balb/c mouse thyroids)

Project description:In this data set, we reported for the first time that huanglongbing disease (HLB) induces major changes in the expression of global genes in flavedo, vascular and juice vesicle tissues of citrus fruit. 68 Total samples were analyzed. cDNA generation, array analysis, and statistical tests were performed as a service at the Interdisciplinary Center for Biotechnology Research (ICBR) Microarray Core facility at the University of Florida (Gainesville, FL). The linear models were used for array analysis (Smyth GK et al. Bioinformatics, 2005, 2067-2075). The linear models were firstly used to assess differential expression, and then an empirical Bayes method was used to moderate the standard errors. 13 comparisons were performed for the study. The comparisons in Citrus sinensis cv. Hamlin included: SC vs. CC (genes that respond to infection in symptomatic vascular core); SJV vs. CJV (genes that respond to infection in symptomatic juice vesicle); SS vs. CS (genes that respond to infection in symptomatic seed); SP vs. CP (genes that respond to infection in symptomatic peel). The comparisons in Citrus sinensis cv. Valencia included: SP vs. HP (genes that respond to infection in symptomatic peel); ASP vs. HP (genes that respond to infection in asymptomatic peel); SP vs. ASP (genes that respond to infection in symptomatic peel compared to asymptomatic peel); SC vs. HC (genes that respond to infection in symptomatic vascular core); ASC vs. HC (genes that respond to infection in asymptomatic vascular core); SC vs. ASC (genes that respond to infection in symptomatic vascular core compared to asymptomatic vascular core); SJV vs. HJV (genes that respond to infection in symptomatic juice vesicle); ASJV vs. HJV (genes that respond to infection in asymptomatic juice vesicle); SJV vs. ASJV (genes that respond to infection in symptomatic juice vesicle compared to asymptomatic juice vesicle). ESTs with significant expression changes (P value <0.001; false discovery rate <0.01 with equal or higher than 2-fold changes in expression) were selected for further analysis.

Project description:Transcriptomic profiling of normal mouse thyroid tissue following 211At irradiation Introduction The cellular response to stimuli can be studied on different molecular levels, including gene expression regulation. RNA microarray is a high-throughput technique that enables comparison of genome-wide transcriptional status between samples. 211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. Metabolically released 211At accumulates in the thyroid gland, which is one of the main critical organs for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on transcriptional expression in mouse thyroid gland. Method BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean absorbed doses to thyroid of 0.023, 0.32, and 1.4 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively, resulting in mean absorbed doses to thyroid of 1.4 Gy. Animals were killed through cardiac puncture under anesthesia, and thyroids were removed and snap-frozen. Total RNA was extracted from pooled thyroid tissue samples and mRNA levels were determined with the Illumina RNA microarray platform. Nexus Expression 3.0 was used to identify differentially expressed transcripts (adjusted p-value <0.01, fold change >1.5) and enriched GO terms (p-value <0.05) between irradiated groups and controls. Results In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose when the exposure time was 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. This suggests that initial dose-rate (thus injected activity) is an important parameter in radiation-induced responses. Furthermore, the regulation profiles of groups administered 1.7 kBq were similar. Few previously proposed radiation responsive genes were identified in the present study, but, e.g. Gadd45g and Cdkn1a were among the regulated genes identified in the present study. A response involving immunological processes was identified especially at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy). Conclusion The present study allowed a comprehensive assessment of how variations in exposure parameters affect transcriptional regulation. The regulation profiles were dependent on both absorbed dose and time after exposure, but, initial dose-rate was the most influential parameter. Functional annotation of regulated genes revealed exposure-specific effects on biological processes. Additionally, we have identified several recurrently regulated genes after 211At exposure that may play a role in how mouse thyroid tissue responds to 211At exposure. Introduction The cellular response to stimuli can be studied on different molecular levels, including gene expression regulation. RNA microarray is a high-throughput technique that enables comparison of genome-wide transcriptional status between samples. 211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. Metabolically released 211At accumulates in the thyroid gland, which is one of the main critical organs for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on transcriptional expression in mouse thyroid gland. Method BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean absorbed doses to thyroid of 0.023, 0.32, and 1.4 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively, resulting in mean absorbed doses to thyroid of 1.4 Gy. Animals were killed through cardiac puncture under anesthesia, and thyroids were removed and snap-frozen. Total RNA was extracted from pooled thyroid tissue samples and mRNA levels were determined with the Illumina RNA microarray platform. Nexus Expression 3.0 was used to identify differentially expressed transcripts (adjusted p-value <0.01, fold change >1.5) and enriched GO terms (p-value <0.05) between irradiated groups and controls. Results In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose when the exposure time was 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. This suggests that initial dose-rate (thus injected activity) is an important parameter in radiation-induced responses. Furthermore, the regulation profiles of groups administered 1.7 kBq were similar. Few previously proposed radiation responsive genes were identified in the present study, but, e.g. Gadd45g and Cdkn1a were among the regulated genes identified in the present study. A response involving immunological processes was identified especially at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy). Conclusion The present study allowed a comprehensive assessment of how variations in exposure parameters affect transcriptional regulation. The regulation profiles were dependent on both absorbed dose and time after exposure, but, initial dose-rate was the most influential parameter. Functional annotation of regulated genes revealed exposure-specific effects on biological processes. Additionally, we have identified several recurrently regulated genes after 211At exposure that may play a role in how mouse thyroid tissue responds to 211At exposure.

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Symptomatic Domoic Acid exposure in zebrafish

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