11 research outputs found
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 AgNO<sub>3</sub> 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. AgNO<sub>3</sub> and PVP-AgNP exposed fish had common and
distinct effects consistent with both intact nanoparticles and dissolved
silver causing effects. PVP-AgNPs and AgNO<sub>3</sub> both affected
pathways involved in Na<sup>+</sup>, K<sup>+</sup>, and H<sup>+</sup> 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. AgNO<sub>3</sub> 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