Jiangxin Wang

The impact of ZnO nanoparticle aggregates on the embryonic development of zebrafish (Danio rerio)

With extensive use of metal oxide nanoparticles (NPs) in a variety of applications comes a higher potential of release into aquatic environments. NPs tend to form much larger aggregates in water, which are expected to settle down to the bottom of the water column and possibly get mixed with the sediments. However, little is known about the environmental impacts and biological effects of these aggregated NPs in the sediment column. In this study, we examined the sedimentation of nanoscale ZnO particles (nZnO) in zebrafish culture medium, and assessed the toxicity of settled nZnO aggregates on developing zebrafish embryos and larvae. Given the known dissolution of nZnO particles to release Zn(2+), we also assessed the toxic effect of soluble Zn(2+) in this organism. We demonstrated that within 48 h, micron-sized nZnO aggregates were formed and settled out of the culture medium. These aggregates were found to exert dose-dependent toxicity to zebrafish embryos and larvae, reducing the hatching rate and causing pericardial edema. The observed toxicity of the nZnO aggregates was not likely a result solely of particle dissolution, as soluble Zn(2+) alone caused much less toxicity to zebrafish embryos than nZnO. Instead, the combination of both nZnO and Zn(2+) may contribute to the embryonic toxicity, possibly by increasing reactive oxidative species (ROS) and/or compromising the cellular oxidative stress response. Interestingly, we demonstrated that one type of formulated sediments could mitigate the toxicity of nZnO aggregates, highlighting a possible countermeasure to reduce the adverse impact of nZnO aggregates on the environment.

Trophic transfer of TiO2 nanoparticles from daphnia to zebrafish in a simplified freshwater food chain

The rapid development of nanotechnology and the corresponding increase in the use of manufactured nanomaterials (MNMs) in commercial products have led to concerns about the health risks and environmental impacts of such nanosized materials. One of the most significant and currently not well-understood risks is their potential transfer and magnification in food webs. To address this concern, a simplified model of a freshwater food chain including a low trophic level organism (daphnia, Daphnia magna) and a high trophic level organism (zebrafish, Danio rerio) was established. Our results provide the first direct evidence that nanoscale TiO(2) particles (nTiO(2)) can transfer from D. magna to D. rerio by dietary exposure. However, no biomagnifications of nTiO(2) was observed in this simplified food chain because the values of the biomagnification factors (BMF) in this study (0.024 and 0.009) were all less than one. Compared to the dietary intake, D. rerio could accumulate nTiO(2) by aqueous exposure with high bioaccumulation factors (BCFs) of 25.38 and 181.38 for 0.1 and 1.0mgL(-1) exposure groups, respectively. Nevertheless, higher body burden of nTiO(2) in the dietary exposure groups than that in the aqueous exposure groups demonstrated that dietary intake may constitute a major route of potential nanomaterial exposure for a higher trophic level of aquatic organisms. This study represents the first examination of the potential food chain transfer and biomagnification of nTiO(2) in an aquatic ecosystem.

Toxicity assessment of manufactured nanomaterials using the unicellular green alga Chlamydomonas reinhardtii

With the rapid development of nanotechnology, there is an increasing risk of human and environmental exposure to nanotechnology-based materials and products. As water resources are particularly vulnerable to direct and indirect contamination of nonomaterials (NMs), the potential toxicity and environmental implication of NMs to aquatic organisms must be evaluated. In this study, we assessed potential toxicity of two commercially used NMs, titanium dioxide (TiO(2)) and quantum dots (QDs), using the unicellular green alga Chlamydomonas reinhartii as a model system. The response of the organism to NMs was assessed at physiological, biochemical, and molecular genetic levels. Growth kinetics showed that growth inhibition occurred during the first two to three days of cultivation in the presence of TiO(2) or QDs. Measurements of lipid peroxidation measurement indicated that oxidative stress of the cells occurred as early as 6 h after exposure to TiO(2) or QDs. The transcriptional expression profiling of four stress response genes (sod1, gpx, cat, and ptox2) revealed that transient up-regulation of these genes occurred in cultures containing as low as 1.0 mg L(-1) of TiO(2) or 0.1 mg L(-1) of QDs, and the maximum transcripts of cat, sod1, gpx, and ptox2 occurred at 1.5, 3, 3, and 6 h, respectively, and were proportional to the initial concentration of the NMs. As the cultures continued, recovery in growth was observed and the extent of recovery, as indicated by the final cell concentration, was dosage-dependent. QDs were found to be more toxic to Chlamydomonas cells than TiO(2) under our experimental conditions.

Disruption of zebrafish (Danio rerio) reproduction upon chronic exposure to TiO2 nanoparticles

As common engineered nanomaterials, TiO(2) nanoparticles (nTiO(2)) are usually perceived as non-toxic, and have already been widely used in many products and applications. Such a perception might have been shaped by some short-term studies that revealed no/low toxicity of nTiO(2) to cells and eco-relevant organisms. However, given the ultimate release of nTiO(2) into the aquatic environment, which can act as a sink for engineered nanoparticles, their long-term impact on the environment and human health is still a concern and deserves more research efforts. Here, for the first time, we demonstrate that chronic exposure of zebrafish to 0.1 mg L(-1) nTiO(2), can significantly impair zebrafish reproduction. For instance, there was a 29.5% reduction in the cumulative number of zebrafish eggs after 13 weeks of nTiO(2) exposure. Thus, we provided timely information on indicating a serious risk of reproductive impairment of environments contaminated with low levels of nTiO(2) on aquatic organisms, leading to alterations in population dynamics and aquatic ecosystem balance, and thus warrants a careful scrutiny on toxicity assessment of nTiO(2), especially their long-term impact.

Identifying biologically relevant genes via multiple heterogeneous data sources

Selection of genes that are differentially expressed and critical to a particular biological process has been a major challenge in post-array analysis. Recent development in bioinformatics has made various data sources available such as mRNA and miRNA expression profiles, biological pathway and gene annotation, etc. Efficient and effective integration of multiple data sources helps enrich our knowledge about the involved samples and genes for selecting genes bearing significant biological relevance. In this work, we studied a novel problem of multi-source gene selection: given multiple heterogeneous data sources (or data sets), select genes from expression profiles by integrating information from various data sources. We investigated how to effectively employ information contained in multiple data sources to extract an intrinsic global geometric pattern and use it in covariance analysis for gene selection. We designed and conducted experiments to systematically compare the proposed approach with representative methods in terms of statistical and biological significance, and showed the efficacy and potential of the proposed approach with promising findings.

Application of embryonic and adult zebrafish for nanotoxicity assessment.

As an emerging model for toxicological studies, zebrafish has been explored for nanotoxicity assessment. In addition to endpoint examination of embryo/fish mortality and/or developmental disorders, molecular analyses of differential gene expression have also been employed to evaluate toxic effects associated with the exposure to nanomaterials. Here, we describe zebrafish-based assays, including both embryo and adult, for evaluation of nanotoxicity caused by metal oxide nanoparticles (NPs), in particular, zinc oxide (ZnO) and titanium oxide (TiO(2)) nanoparticles.

Integrating Knowledge in Search of Biologically Relevant Genes

Gene selection aims at detecting biologically relevant genes to assist biologists research. The cDNA Microarray data used in gene selection is usually wide. With more than ten thousand genes, but only less than a hundred of samples, many biologically irrelevant genes can gain their statistical relevance by sheer randomness. Moreover, even for genes that are biologically relevant, biologists often prefer the trigger to the fire. Addressing these problems goes beyond what the cDNA Microarray can offer and necessitates the use of additional information. Recent developments in bioinformatics have made various knowledge sources available, such as the KEGG pathway repository and Gene Ontology database. Integrating different types of knowledge for gene selection could provide more information about genes and samples. In this work, we propose a novel framework to integrate different types of knowledge for identifying biologically relevant genes. The framework converts different types of external knowledge to its internal knowledge, which can be used to rank genes. Upon obtaining the ranking lists, it aggregates them via a probabilistic model and generates a final ranking list. Experimental results from our study on acute lymphoblastic leukemia demonstrate the novelty and efficacy of the proposed framework and show that using different types of knowledge together can help detect biologically relevant genes.