Joel A. Pedersen

Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles

Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of Mte- and soil-bound prions. We establish that prions bound to Mte are orally bioavailable, and that, unexpectedly, binding to Mte significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Cox proportional hazards modeling revealed that across the doses of TSE agent tested, Mte increased the effective infectious titer by a factor of 680 relative to unbound agent. Oral exposure to Mte-associated prions led to TSE development in experimental animals even at doses too low to produce clinical symptoms in the absence of the mineral. We tested the oral infectivity of prions bound to three whole soils differing in texture, mineralogy, and organic carbon content and found soil-bound prions to be orally infectious. Two of the three soils increased oral transmission of disease, and the infectivity of agent bound to the third organic carbon-rich soil was equivalent to that of unbound agent. Enhanced transmissibility of soil-bound prions may explain the environmental spread of some TSEs despite the presumably low levels shed into the environment. Association of prions with inorganic microparticles represents a novel means by which their oral transmission is enhanced relative to unbound agent.

Titanium dioxide nanoparticles produce phototoxicity in the developing zebrafish

Abstract Exposure of humans and other organisms to nanomaterials is increasing exponentially. It is important, but difficult, to predict the biological consequences of these exposures. We hypothesized that the unique chemical properties that make nanoparticles useful might also be the key in predicting their biological impact. To investigate this, we chose titanium dioxide nanoparticles (TiO2NPs) and developing zebrafish embryos as model systems. TiO2NPs absorb photons to generate electron–hole pairs that react with water and oxygen to form cytotoxic reactive oxygen species (ROS). Here, we show that the exposure of zebrafish embryos to TiO2NPs produces malformation and death, but only if the fish are also illuminated. TiO2NPs are taken up into the developing fish, but the egg chorion is a barrier to uptake until the embryos hatch. Chemical probes and a transgenic reporter line confirm photo-dependent production of ROS in vivo, and the addition of an ROS scavenger rescues fish embryos from toxicity. To our knowledge, this is the first study to show a photo-dependent toxic response in a whole organism from exposure to TiO2NPs. Of further significance, our study highlights the relationship between the property of the material that makes it useful and the biological effect that is produced. This concept should serve as a guide for future nanotoxicological studies aiming to identify potential hazardous effects on organisms.

Influence of Humic Acid on Titanium Dioxide Nanoparticle Toxicity to Developing Zebrafish

Titanium dioxide nanoparticle (TiO2NP) suspension stability can be altered by adsorption of dissolved organic matter (DOM). This is expected to impact their environmental fate and bioavailability. To date, the influence of DOM on the toxicity of TiO2NPs to aquatic vertebrates has not been reported. We examined the impact of Suwannee River humic acid (HA) on the toxicity of TiO2NPs to developing zebrafish (Danio rerio) in the dark and under simulated sunlight illumination. Adsorption of HA increased suspension stability and decreased TiO2NP exposure. TiO2NPs were more toxic in the presence of HA. In the absence of simulated sunlight, a small but significant increase in lethality was observed in fish exposed to TiO2NPs in the presence of HA. Under simulated sunlight illumination, photocatalytic degradation of HA reduced suspension stability. Despite the lower concentrations of Ti associated with fish in the treatments containing HA, under simulated sunlight illumination, median lethal concentrations were lower and oxidative DNA damage was elevated relative to fish exposed to TiO2NPs in the absence of HA. This study demonstrates the importance of considering environmental factors (i.e., exposure to sunlight, adsorption of DOM) when assessing the potential risks posed by engineered nanomaterials in the environment.

Occurrence of tetracycline resistance genes in aquaculture facilities with varying use of oxytetracycline

The contribution of human activities to environmental reservoirs of antibiotic resistance is poorly understood. The purpose of this study was to determine if oxytetracycline (OTC) use in aquaculture facilities increased the detection frequency (i.e., prevalence) of tetracycline resistance (tetR) genes relative to facilities with no recent OTC treatment. We used polymerase chain reaction to screen water and sediment from four noncommercial fish farms in northwestern Wisconsin for the presence of ten tetR determinants: tet(A), tet(B), tet(D), tet(E), tet(G), tet(M), tet(O), tet(Q), tet(S), and tet(W). Water from farms with recent OTC use had significantly higher tetR detection frequencies than did water from farms without recent OTC use, with prevalence in raceways and rearing ponds of farms with recent OTC use exceeding by more than twofold that of farms not using OTC. Effluent from all farms, regardless of treatment regime, had higher tetR detection frequencies than their corresponding influent for all genes, but the specific combinations of tetR genes detected in a sample were not different from their corresponding influent. Although OTC use was associated with the increased occurrence and diversity of tetR genes in water samples, it was not found to relate to tetR gene occurrence in sediment samples. Sediment samples from facilities with no recent OTC use had significantly higher frequencies of tetR gene detection than did samples from facilities with recent OTC use. All of the tetR genes were detected in both the medicated and nonmedicated feed samples analyzed in this study. These findings suggest that both OTC treatment in aquaculture facilities and the farms themselves may be sources of tetR gene introduction to the environment. To our knowledge, this is the first study to use genotypic and cultivation-independent methods to examine tetR gene occurrence associated with OTC use in aquaculture.

Root Uptake of Pharmaceuticals and Personal Care Product Ingredients

Crops irrigated with reclaimed wastewater or grown in biosolids-amended soils may take up pharmaceuticals and personal care product ingredients (PPCPs) through their roots. The uptake pathways followed by PPCPs and the propensity for these compounds to bioaccumulate in food crops are still not well understood. In this critical review, we discuss processes expected to influence root uptake of PPCPs, evaluate current literature on uptake of PPCPs, assess models for predicting plant uptake of these compounds, and provide recommendations for future research, highlighting processes warranting study that hold promise for improving mechanistic understanding of plant uptake of PPCPs. We find that many processes that are expected to influence PPCP uptake and accumulation have received little study, particularly rhizosphere interactions, in planta transformations, and physicochemical properties beyond lipophilicity (as measured by Kow). Data gaps and discrepancies in methodology and reporting have so far hindered development of models that accurately predict plant uptake of PPCPs. Topics warranting investigation in future research include the influence of rhizosphere processes on uptake, determining mechanisms of uptake and accumulation, in planta transformations, the effects of PPCPs on plants, and the development of predictive models.

Transformation of Sulfamethazine by Manganese Oxide in Aqueous Solution

The transformation of the sulfonamide antimicrobial sulfamethazine (SMZ) by a synthetic analogue of the birnessite-family mineral vernadite (δ-MnO(2)) was studied. The observed pseudo-first-order reaction constants (k(obs)) decreased as the pH increased from 4.0 to 5.6, consistent with the decline in δ-MnO(2) reduction potential with increasing pH. Molecular oxygen accelerated SMZ transformation by δ-MnO(2) and influenced the transformation product distribution. Increases in the Na(+) concentration produced declines in k(obs). Transformation products identified by tandem mass spectrometry and the use of (13)C-labeled SMZ included an azo dimer self-coupling product and SO(2) extrusion products. Product analysis and density functional theory calculations are consistent with surface precursor complex formation followed by single-electron transfer from SMZ to δ-MnO(2) to produce SMZ radical species. Sulfamethazine radicals undergo further transformation by at least two pathways: radical-radical self-coupling or a Smiles-type rearrangement with O addition and then extrusion of SO(3). Experiments conducted in H(2)(18)O or in the presence of (18)O(2)(aq) demonstrated that oxygen both from the lattice of as-synthesized δ-MnO(2) and initially present as dissolved oxygen reacted with SMZ. The study results suggest that the oxic state and pH of soil and sediment environments can be expected to influence manganese oxide-mediated transformation of sulfonamide antimicrobials.

Sorption of Sulfonamide Antimicrobial Agents to Humic Acid–Clay Complexes

The interaction of sulfonamide antimicrobial agents with smectite clay minerals and humic acid (HA)-clay complexes was investigated in batch experiments to assess the influence of adsorbed humic acid on sulfonamide sorption. Soil HA-clay complexes were produced at HA:clay ratios of 1:5, 1:50, and 1:100 (w/w). Vibrational and electronic spectroscopy indicated the preferential adsorption of polar and aliphatic components of HA to smectite surfaces, a phenomenon most readily discerned at the two lower HA:clay ratios (1:50 and 1:100). Humic acid adsorption to smectite clay minerals enhanced sulfamethazine [2-(p-aminobenzenesulfonamido)-4,6-dimethyl pyrimidine] sorption, especially at the highest HA:clay ratio (1:5). Sulfamethazine sorption to adsorbed HA generally increased with the abundance of carboxyl (and possibly other O- and N-containing) moieties and aliphatic carbon content. Both the smectite surface and the adsorbed humic acids contributed to sulfamethazine sorption-desorption hysteresis; hysteresis in sulfamethazine sorption to the adsorbed humic acids was equal to or larger than for adsorption to the smectites. Competitive sorption with a structurally similar sulfonamide antimicrobial was apparent only at high competitor concentrations. This study indicates that sorption to organic carbon and clay mineral surfaces as well as the hysteretic sorption behavior warrant consideration in predicting the transport of these antimicrobial agents in soils and subsurface environments.

A Citric Acid-Derived Ligand for Modular Functionalization of Metal Oxide Surfaces via “Click” Chemistry

Citric acid is a widely used surface-modifying ligand for growth and processing of a variety of nanoparticles; however, the inability to easily prepare derivatives of this molecule has restricted the development of versatile chemistries for nanoparticle surface functionalization. Here, we report the design and synthesis of a citric acid derivative bearing an alkyne group and demonstrate that this molecule provides the ability to achieve stable, multidentate carboxylate binding to metal oxide nanoparticles, while also enabling subsequent multistep chemistry via the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The broad utility of this strategy for the modular functionalization of metal oxide surfaces was demonstrated by its application in the CuAAC modification of ZnO, Fe(2)O(3), TiO(2), and WO(3) nanoparticles.

Assessing Landscape Condition Relative to Water Resources in the Western United States: A Strategic Approach

The Environmental Monitoring and Assessment Program (EMAP) is proposing an ambitious agenda to assess the status of streams and estuaries in a 12-State area of the western United States by the end of 2003. Additionally, EMAP is proposing to access landscape conditions as they relate to stream and estuary conditions across the west. The goal of this landscape project is to develop a landscape model that can be used to identify the relative risks of streams and estuaries to potential declines due to watershed-scale, landscape conditions across the west. To do so, requires an understanding of quantitative relationships between landscape composition and pattern metrics and parameters of stream and estuary conditions. This paper describes a strategic approach for evaluating the degree to which landscape composition and pattern influence stream and estuary condition, and the development and implementation of a spatially-distributed, landscape analysis approach.

Biological Responses to Engineered Nanomaterials: Needs for the Next Decade.

The interaction of nanomaterials with biomolecules, cells, and organisms is an enormously vital area of current research, with applications in nanoenabled diagnostics, imaging agents, therapeutics, and contaminant removal technologies. Yet the potential for adverse biological and environmental impacts of nanomaterial exposure is considerable and needs to be addressed to ensure sustainable development of nanomaterials. In this Outlook four research needs for the next decade are outlined: (i) measurement of the chemical nature of nanomaterials in dynamic, complex aqueous environments; (ii) real-time measurements of nanomaterial–biological interactions with chemical specificity; (iii) delineation of molecular modes of action for nanomaterial effects on living systems as functions of nanomaterial properties; and (iv) an integrated systems approach that includes computation and simulation across orders of magnitude in time and space.