Nicholas S. Fisher

The Assimilation of Elements Ingested by Marine Copepods

The efficiency with which a variety of ingested elements (Ag, Am, C, Cd, P, S, Se, and Zn) were assimilated in marine calanoid copepods fed uniformly radiolabeled diatoms ranged from 0.9% for Am to 97.1% for Se. Assimilation efficiencies were directly related to the cytoplasmic content of the diatoms. This relation indicates that the animals obtained nearly all their nutrition from this source. The results suggest that these zooplankton, which have short gut residence times, have developed a gut lining and digestive strategy that provides for assimilation of only soluble material. Because the fraction of total cellular protein in the cytoplasm of the diatoms increased markedly with culture age, copepods feeding on senescent cells should obtain more protein than those feeding on rapidly dividing cells. Elements that are appreciably incorporated into algal cytoplasm and assimilated in zooplankton should be recycled in surface waters and have longer oceanic residence times than elements bound to cell surfaces.

Trace element trophic transfer in aquatic organisms: A critique of the kinetic model approach

The bioaccumulation of trace elements in aquatic organisms can be described with a kinetic model that includes linear expressions for uptake and elimination from dissolved and dietary sources. Within this model, trace element trophic transfer is described by four parameters: the weight-specific ingestion rate (IR); the assimilation efficiency (AE); the physiological loss rate constant (ke); and the weight-specific growth rate (g). These four parameters define the trace element trophic transfer potential (TTP = IR.AE/[ke + g]) which is equal to the ratio of the steady-state trace element concentration in a consumer due to trophic accumulation to that in its prey. Recent work devoted to the quantification of AE and ke for a variety of trace elements in aquatic invertebrates has provided the data needed for comparative studies of trace element trophic transfer among different species and trophic levels and, in at least one group of aquatic consumers (marine bivalves), sensitivity analyses and field tests of kinetic bioaccumulation models. Analysis of the trophic transfer potentials of trace elements for which data are available in zooplankton, bivalves, and fish, suggests that slight variations in assimilation efficiency or elimination rate constant may determine whether or not some trace elements (Cd, Se, and Zn) are biomagnified. A linear, single-compartment model may not be appropriate for fish which, unlike many aquatic invertebrates, have a large mass of tissue in which the concentrations of most trace elements are subject to feedback regulation.

Fukushima-derived radionuclides in the ocean and biota off Japan

The Tōhoku earthquake and tsunami of March 11, 2011, resulted in unprecedented radioactivity releases from the Fukushima Dai-ichi nuclear power plants to the Northwest Pacific Ocean. Results are presented here from an international study of radionuclide contaminants in surface and subsurface waters, as well as in zooplankton and fish, off Japan in June 2011. A major finding is detection of Fukushima-derived 134Cs and 137Cs throughout waters 30–600 km offshore, with the highest activities associated with near-shore eddies and the Kuroshio Current acting as a southern boundary for transport. Fukushima-derived Cs isotopes were also detected in zooplankton and mesopelagic fish, and unique to this study we also find 110mAg in zooplankton. Vertical profiles are used to calculate a total inventory of ∼2 PBq 137Cs in an ocean area of 150,000 km2. Our results can only be understood in the context of our drifter data and an oceanographic model that shows rapid advection of contaminants further out in the Pacific. Importantly, our data are consistent with higher estimates of the magnitude of Fukushima fallout and direct releases [Stohl et al. (2011) Atmos Chem Phys Discuss 11:28319–28394; Bailly du Bois et al. (2011) J Environ Radioact, 10.1016/j.jenvrad.2011.11.015]. We address risks to public health and marine biota by showing that though Cs isotopes are elevated 10–1,000× over prior levels in waters off Japan, radiation risks due to these radionuclides are below those generally considered harmful to marine animals and human consumers, and even below those from naturally occurring radionuclides.

Delineating metal accumulation pathways for marine invertebrates

Delineating the routes of metal uptake in marine invertebrates is important for understanding metal bioaccumulation and toxicity and for setting appropriate water and sediment quality criteria. Trace element biogeochemical cycling can also be affected if the rates of metal uptake and regeneration by marine animals are dependent on the routes of metal accumulation. In this paper we review recent studies on the pathways of metal accumulation in marine invertebrates. Both food and water can dominate metal accumulation, depending on the species, metal and food sources. Trace elements which exist in seawater primarily in anionic forms (e.g. As and Se) are mainly accumulated from food. For metals that tend to associate with protein, uptake from water can be an important source. Kinetic modeling has recently been used to quantitatively separate the pathways of metal uptake in a few marine invertebrates. This approach requires measurements of several physiological parameters, including metal assimilation efficiencies (AE) from ingested food, metal uptake rates from the dissolved phase, and metal efflux rates (physiological turnover rates) in animals. For suspension feeders such as mussels and copepods, uptake from the dissolved phase and food ingestion can be equally important to metal accumulation. Metal AE and partition coefficients for suspended particles, which are dependent on many environmental conditions, can critically affect the exposure pathways of metals. For marine surface deposit feeding polychaetes such as Nereis succinea, nearly all metals are obtained from ingestion of sediments, largely because of their high ingestion rates and low uptake from solution. The bioavailability of metals from food and the trophic transfer of metals must be considered in establishing water and sediment quality.

Stoichiometric controls of mercury dilution by growth.

Rapid growth could significantly reduce methylmercury (MeHg) concentrations in aquatic organisms by causing a greater than proportional gain in biomass relative to MeHg (somatic growth dilution). We hypothesized that rapid growth from the consumption of high-quality algae, defined by algal nutrient stoichiometry, reduces MeHg concentrations in zooplankton, a major source of MeHg for lake fish. Using a MeHg radiotracer, we measured changes in MeHg concentrations, growth and ingestion rates in juvenile Daphnia pulex fed either high (C:P = 139) or low-quality (C:P = 1317) algae (Ankistrodesmus falcatus) for 5 d. We estimated Daphnia steady-state MeHg concentrations, using a biokinetic model parameterized with experimental rates. Daphnia MeHg assimilation efficiencies (≈95%) and release rates (0.04 d−1) were unaffected by algal nutrient quality. However, Daphnia growth rate was 3.5 times greater when fed high-quality algae, resulting in pronounced somatic growth dilution. Steady-state MeHg concentrations in Daphnia that consumed high-quality algae were one-third those of Daphnia that consumed low-quality algae due to higher growth and slightly lower ingestion rates. Our findings show that rapid growth from high-quality food consumption can significantly reduce the accumulation and trophic transfer of MeHg in freshwater food webs.

EFFECT OF MORPHOLOGY OF ZNO NANOSTRUCTURES ON THEIR TOXICITY TO MARINE ALGAE

The influence of ZnO nanoparticle morphology on its toxicity for marine diatoms was evaluated. Four ZnO nanoparticle motifs, possessing distinctive sizes and shapes, were synthesized without adding surfactants. Diameters of ZnO spheres ranged from 6.3 nm to 15.7 nm, and lengths of rod-shaped particles were 242 nm to 862 nm. Their effects on the growth of the marine diatoms, Thalassiosira pseudonana, Chaetoceros gracilis, and Phaeodactylum tricornutum, were determined in laboratory cultures. Between 4.1 and 4.9% of the Zn from all types of nanoparticles dissolved within 72 h and was neither concentration dependent nor morphology dependent. Addition of all nanoparticles at all concentrations tested stopped growth of T. pseudonana and C. gracilis, whereas P. tricornutum was the least sensitive, with its growth rate inversely proportional to nanoparticle concentration. Bioaccumulation of Zn released from nanoparticles in T. pseudonana was sufficient to kill this diatom. The toxicity of rod-shaped particles to P. triocornutum was noted to be greater than that of the spheres. The overall results suggest that toxicity studies assessing the effects of nanoparticles on aquatic organisms need to consider both the dissolution of these particles and the cellular interaction of nanoparticle aggregates.

Polychlorinated biphenyls and DDT alter species composition in mixed cultures of algae.

Either DDT or polychlorinated biphenyls were added to mixed cultures containing a marine diatom and a marine green alga that were sensitive and resistant, respectively, to these organochlorine compounds. The diatom grew faster and was therefore dominant in control cultures, but its dominance diminished in treated cultures, even at concentrations of chlorinated hydrocarbons that had no apparent effect in pure cultures. Such stable pollutants could disrupt the species composition of phytoplankton communities, thereby affecting whole eco-systems.

Effects of copper and zinc on growth, morphology, and metabolism of Asterionella japonica (Cleve) 1☆

When exposed to elevated levels of copper or zinc, the diatom Asterionella japonica (Cleve) showed a reduced cell division rate and a marked increase in cell size. Metal-treated cells had greater cell volumes, dry weights, carbon, nitrogen, chlorophyll, and DNA contents, all in approximately the same proportion as control cells. Two protoplasts often appeared to be contained within one frustule. Metal-treated cells photosynthesized at near-normal rates on a per chlorophyll basis and above normal rates on a per cell basis. Excretion of photosynthetically fixed carbon was depressed by metal treatment; 10–22% of fixed carbon was excreted in control cells and typically less than 1% in treated cells. Thus, metal-treated cells showed an uncoupling of photosynthesis from cell division and continued to enlarge when fixed carbon could not be excreted or utilized in cell division. Uptake of sulphate and silicic acid proceeded at slower rates than other processes (e.g., nitrogen uptake or photosynthesis) in copper-treated cells. Free amino acids in copper-treated cells totalled ≈ 10% of control cell levels, with greatest proportional declines in methionine, cysteine, aspartic acid, valine, and isoleucine. Copper-treated cells resuspended in fresh medium shrank to normal size when exposed to methionine (which they accumulated), although cell division rates did not return to normal. These cells excreted 2–3 times as much fixed carbon as comparable EDTA-treated or untreated cells, neither of which decreased in size. Copper-treated cells appeared indistinguishable from silicon-limited cells (i.e., cells not dividing for lack of silicon) in a copper-free medium. Cells treated with the sulfhydryl binder PCMB divided at reduced rates and also swelled in a manner comparable to copper-treated cells. The results suggest that toxic metals may bind to sulfhydryl groups on cell membranes, impairing normal membrane function and reducing silicic acid uptake and amino-acid synthesis, thereby resulting in depressed cell division rates.

Polychlorinated Biphenyls: Toxicity to Certain Phytoplankters

The growth rates of two species of marine diatoms were reduced by polychlorinated biphenyls (PCBs), widespread pollutants of the marine environment, at concentrations as low as 10 to 25 parts per billion. In contrast, a marine green alga and two species of freshwater algae were not inhibited at these or higher concentrations. The sensitivity of these species to PCBs paralleled their sensitivity to DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane].

Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria

There is an urgent need for new antimalarial drugs with novel mechanisms of action to deliver effective control and eradication programs. Parasite resistance to all existing antimalarial classes, including the artemisinins, has been reported during their clinical use. A failure to generate new antimalarials with novel mechanisms of action that circumvent the current resistance challenges will contribute to a resurgence in the disease which would represent a global health emergency. Here we present a unique generation of quinolone lead antimalarials with a dual mechanism of action against two respiratory enzymes, NADH:ubiquinone oxidoreductase (Plasmodium falciparum NDH2) and cytochrome bc1. Inhibitor specificity for the two enzymes can be controlled subtly by manipulation of the privileged quinolone core at the 2 or 3 position. Inhibitors display potent (nanomolar) activity against both parasite enzymes and against multidrug-resistant P. falciparum parasites as evidenced by rapid and selective depolarization of the parasite mitochondrial membrane potential, leading to a disruption of pyrimidine metabolism and parasite death. Several analogs also display activity against liver-stage parasites (Plasmodium cynomolgi) as well as transmission-blocking properties. Lead optimized molecules also display potent oral antimalarial activity in the Plasmodium berghei mouse malaria model associated with favorable pharmacokinetic features that are aligned with a single-dose treatment. The ease and low cost of synthesis of these inhibitors fulfill the target product profile for the generation of a potent, safe, and inexpensive drug with the potential for eventual clinical deployment in the control and eradication of falciparum malaria.