Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition-2

<p><b>Copyright information:</b></p><p>Taken from "Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition"</p><p>http://www.biomedcentral.com/1471-2164/9/S1/S16</p><p>BMC Genomics 2008;9(Suppl 1):S16-S16.</p><p>Published online 20 Mar 2008</p><p>PMCID:PMC2386058.</p><p></p

Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition-3

<p><b>Copyright information:</b></p><p>Taken from "Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition"</p><p>http://www.biomedcentral.com/1471-2164/9/S1/S16</p><p>BMC Genomics 2008;9(Suppl 1):S16-S16.</p><p>Published online 20 Mar 2008</p><p>PMCID:PMC2386058.</p><p></p

Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition-1

<p><b>Copyright information:</b></p><p>Taken from "Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition"</p><p>http://www.biomedcentral.com/1471-2164/9/S1/S16</p><p>BMC Genomics 2008;9(Suppl 1):S16-S16.</p><p>Published online 20 Mar 2008</p><p>PMCID:PMC2386058.</p><p></p

Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition-0

<p><b>Copyright information:</b></p><p>Taken from "Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition"</p><p>http://www.biomedcentral.com/1471-2164/9/S1/S16</p><p>BMC Genomics 2008;9(Suppl 1):S16-S16.</p><p>Published online 20 Mar 2008</p><p>PMCID:PMC2386058.</p><p></p

Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition-4

<p><b>Copyright information:</b></p><p>Taken from "Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition"</p><p>http://www.biomedcentral.com/1471-2164/9/S1/S16</p><p>BMC Genomics 2008;9(Suppl 1):S16-S16.</p><p>Published online 20 Mar 2008</p><p>PMCID:PMC2386058.</p><p></p

A Systems Toxicology Approach to Elucidate the Mechanisms Involved in RDX Species-Specific Sensitivity

Interspecies uncertainty factors in ecological risk assessment provide conservative estimates of risk where limited or no toxicity data is available. We quantitatively examined the validity of interspecies uncertainty factors by comparing the responses of zebrafish (<i>Danio rerio</i>) and fathead minnow (<i>Pimephales promelas</i>) to the energetic compound 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), a known neurotoxicant. Relative toxicity was measured through transcriptional, morphological, and behavioral end points in zebrafish and fathead minnow fry exposed for 96 h to RDX concentrations ranging from 0.9 to 27.7 mg/L. Spinal deformities and lethality occurred at 1.8 and 3.5 mg/L RDX respectively for fathead minnow and at 13.8 and 27.7 mg/L for zebrafish, indicating that zebrafish have an 8-fold greater tolerance for RDX than fathead minnow fry. The number and magnitude of differentially expressed transcripts increased with increasing RDX concentration for both species. Differentially expressed genes were enriched in functions related to neurological disease, oxidative-stress, acute-phase response, vitamin/mineral metabolism and skeletal/muscular disorders. Decreased expression of collagen-coding transcripts were associated with spinal deformity and likely involved in sensitivity to RDX. Our work provides a mechanistic explanation for species-specific sensitivity to RDX where zebrafish responded at lower concentrations with greater numbers of functions related to RDX tolerance than fathead minnow. While the 10-fold interspecies uncertainty factor does provide a reasonable cross-species estimate of toxicity in the present study, the observation that the responses between ZF and FHM are markedly different does initiate a call for concern regarding establishment of broad ecotoxicological conclusions based on model species such as zebrafish

Identification of Metabolic Pathways in <i>Daphnia magna</i> Explaining Hormetic Effects of Selective Serotonin Reuptake Inhibitors and 4‑Nonylphenol Using Transcriptomic and Phenotypic Responses

The molecular mechanisms explaining hormetic effects of selective serotonin reuptake inhibitors (SSRIs) and 4-nonylphenol in <i>Daphnia magna</i> reproduction were studied in juveniles and adults. Transcriptome analyses showed changes in mRNA levels for 1796 genes in juveniles and 1214 genes in adults (out of 15 000 total probes) exposed to two SSRIs (fluoxetine and fluvoxamine) or to 4-nonylphenol. Functional annotation of affected genes was improved by assuming the annotations of putatively homologous <i>Drosophila</i> genes. Self-organizing map analysis and partial least-square regression coupled with selectivity ratio procedures analyses allowed to define groups of genes with specific responses to the different treatments. Differentially expressed genes were analyzed for functional enrichment using Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes databases. Serotonin metabolism, neuronal developmental processes, and carbohydrates and lipid metabolism functional categories appeared as selectively affected by SSRI treatment, whereas 4-nonylphenol deregulated genes from the carbohydrate metabolism and the ecdysone regulatory pathway. These changes in functional and metabolic pathways are consistent with previously reported SSRIs and 4-nonylphenol hormetic effects in <i>D. magna</i>, including a decrease in reserve carbohydrates and an increase in respiratory metabolism

The Good, the Bad, and the Toxic: Approaching Hormesis in <i>Daphnia magna</i> Exposed to an Energetic Compound

A hormetic response is characterized by an opposite effect in small and large doses of chemical exposure, often resulting in seemingly beneficial effects at low doses. Here, we examined the potential mechanisms underlying the hormetic response of <i>Daphnia magna</i> to the energetic trinitrotoluene (TNT). <i>Daphnia magna</i> were exposed to TNT for 21 days, and a significant increase in adult length and number of neonates was identified at low concentrations (0.002–0.22 mg/L TNT), while toxic effects were identified at high concentrations (0.97 mg/L TNT and above). Microarray analysis of <i>D. magna</i> exposed to 0.004, 0.12, and 1.85 mg/L TNT identified effects on lipid metabolism as a potential mechanism underlying hormetic effects. Lipidomic analysis of exposed <i>D. magna</i> supported the hypothesis that TNT exposure affected lipid and fatty acid metabolism, showing that hormetic effects could be related to changes in polyunsaturated fatty acids known to be involved in <i>Daphnia</i> growth and reproduction. Our results show that <i>Daphnia</i> exposed to low levels of TNT presented hormetic growth and reproduction enhancement, while higher TNT concentrations had an opposite effect. Our results also show how a systems approach can help elucidate potential mechanisms of action and adverse outcomes

Differential Effects and Potential Adverse Outcomes of Ionic Silver and Silver Nanoparticles in Vivo and in Vitro

Nanoparticles are of concern because of widespread use, but it is unclear if metal nanoparticles cause effects directly or indirectly. We explored whether polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) cause effects through intact nanoparticles or dissolved silver. Females of the model species fathead minnow (<i>Pimephales promelas</i>) were exposed to either 4.8 μg/L of AgNO₃ or 61.4 μg/L of PVP-AgNPs for 96h. Microarray analyses were used to identify impacted receptors and toxicity pathways in liver and brain tissues that were confirmed using in vitro mammalian assays. AgNO₃ and PVP-AgNP exposed fish had common and distinct effects consistent with both intact nanoparticles and dissolved silver causing effects. PVP-AgNPs and AgNO₃ both affected pathways involved in Na⁺, K⁺, and H⁺ homeostasis and oxidative stress but different neurotoxicity pathways. In vivo effects were supported by PVP-AgNP activation of five in vitro nuclear receptor assays and inhibition of ligand binding to the dopamine receptor. AgNO₃ inhibited ligand binding to adrenergic receptors α1 and α2 and cannabinoid receptor CB1, but had no effect in nuclear receptor assays. PVP-AgNPs have the potential to cause effects both through intact nanoparticles and metal ions, each interacting with different initiating events. Since the in vitro and in vivo assays examined here are commonly used in human and ecological hazard screening, this work suggests that environmental health assessments should consider effects of intact nanoparticles in addition to dissolved metals

Prioritization of Contaminants of Emerging Concern in Wastewater Treatment Plant Discharges Using Chemical:Gene Interactions in Caged Fish

We examined whether contaminants present in surface waters could be prioritized for further assessment by linking the presence of specific chemicals to gene expression changes in exposed fish. Fathead minnows were deployed in cages for 2, 4, or 8 days at three locations near two different wastewater treatment plant discharge sites in the Saint Louis Bay, Duluth, MN and one upstream reference site. The biological impact of 51 chemicals detected in the surface water of 133 targeted chemicals was determined using biochemical endpoints, exposure activity ratios for biological and estrogenic responses, known chemical:gene interactions from biological pathways and knowledge bases, and analysis of the covariance of ovary gene expression with surface water chemistry. Thirty-two chemicals were significantly linked by covariance with expressed genes. No estrogenic impact on biochemical endpoints was observed in male or female minnows. However, bisphenol A (BPA) was identified by chemical:gene covariation as the most impactful estrogenic chemical across all exposure sites. This was consistent with identification of estrogenic effects on gene expression, high BPA exposure activity ratios across all test sites, and historical analysis of the study area. Gene expression analysis also indicated the presence of nontargeted chemicals including chemotherapeutics consistent with a local hospital waste stream. Overall impacts on gene expression appeared to be related to changes in treatment plant function during rain events. This approach appears useful in examining the impacts of complex mixtures on fish and offers a potential route in linking chemical exposure to adverse outcomes that may reduce population sustainability