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Consumption of contaminated Great Lakes fish by pregnant women is associated with decreased birth weight and deficits in cognitive function in their infants and children. These fish contain many known and suspected anthropogenic neurotoxicants, making it difficult to determine which contaminant(s) are responsible for the observed deficits. We have undertaken a series of experiments to determine the relevant toxicants by comparing the neurotoxic effects of two of these contaminants-polychlorinated biphenyls (PCBs) and methylmercury (MeHg)-both of which are recognized neurotoxicants. Striatal punches obtained from adult rat brain were exposed to PCBs only, MeHg only, or the two in combination, and tissue and media concentrations of dopamine (DA) and its metabolites were determined by high performance liquid chromatography. Exposure to PCBs only reduced tissue DA and elevated media DA in a dose-dependent fashion. Exposure to MeHg only did not significantly affect either measure. However, when striatal punches were simultaneously exposed to PCBs and MeHg, there were significantly greater decreases in tissue DA concentrations and elevations in media DA than those caused by PCBs only, in the absence of changes in media lactate dehydrogenase concentrations. Elevations in both tissue and media 3,4-dihydroxyphenylacetic acid concentrations were also observed. We suggest that the significant interactions between these two toxicants may be due to a common site of action (i.e., toxicant-induced increases in intracellular calcium and changes in second messenger systems) that influences DA function. The synergism between these contaminants suggests that future revisions of fish-consumption guidelines should consider contaminant interactions.

Polychlorinated biphenyls (PCBs) reduce tissue dopamine (DA) concentrations and increase media DA concentrations in both in vitro preparations of bovine adrenal chromaffin cells and adult rat striatal tissue. To determine whether these changes also occur in the intact animal, we used in vivo microdialysis to determine changes in concentrations of DA in striatal dialysates from freely moving adult male rats after exposure to 25 mg/kg/day Aroclor 1254 for varying periods of time. We also determined DA concentrations in striatal tissue obtained postmortem from similarly treated animals. The effects of PCBs on dialysate DA concentrations depended on the length of exposure; DA concentrations were significantly elevated after 3 days of exposure and were significantly reduced after exposure for periods of 1 week or longer. On the other hand, striatal tissue concentrations of DA, determined postmortem in rats exposed to PCBs for the same periods of time, were not significantly altered. We suggest that these time-dependent alterations in dialysate DA concentrations a) reflect PCB-induced alterations of both plasma membrane and vesicular DA transporter function; b) provide a more sensitive index of altered central DA function after exposure to PCBs than does measurement of postmortem tissue DA concentrations; and c) play an important role in mediating some PCB-mediated changes in behavior.

Polychlorinated biphenyls (PCBs) and methylmercury (MeHg) are two well-known neurotoxicants which persist in the environment and are commonly found in food destined for human consumption. Children whose mothers regularly consume such contaminated foods, both before and during pregnancy, demonstrate developmental and behavioral deficits associated with PCB and/or MeHg body burdens. Experiments performed in our laboratory demonstrated that combined exposure to PCBs and MeHg results in synergistic reductions in rat brain striatal tissue dopamine (DA) content and elevations in extracellular DA concentrations. Experiments in rat cerebellar granule cells revealed that exposure to PCBs+MeHg resulted in both dose- and time-dependent synergistic and antagonistic elevations in intracellular calcium concentrations. In order to improve our understanding of how these two toxicants may induce these effects, I used rat striatal synaptosomes to examine the potential consequences which PCB-induced increases in intracellular calcium and/or inhibition of dopamine transporters can have on DA. PCBs altered both synaptosomal tissue DA content and media DA concentrations, and intrasynaptosomal calcium. Manipulation of synaptosomal calcium by incubation in nominal calcium free medium or chelation of intracellular calcium, inhibited the ability of PCBs to reduce tissue DA content but did not affect PCB-mediated elevations in media DA concentrations. Because PCBs are known to inhibit monoamine transporter function, the consequences of this inhibition on the neurochemical effects observed following exposure of synaptosomes to PCBs was investigated. PCB-mediated inhibition of the dopamine transporter (DAT) was significantly correlated with both reductions in tissue DA and elevations in media DA concentrations. Inhibition of the vesicular monoamine transporter only correlated with an increase in tissue+media dihydroxyphenylacetic acid concentrations. Thus, PCB-induced alterations in tissue DA appear to be partly calcium-dependent and both tissue and media DA alterations appear to be partially mediated by the ability of PCBs to inhibit the uptake of DA by DAT. These studies provide a more complete understanding of the mechanistic pathways through which PCBs alter neurochemical function. Improving our understanding of how PCBs alter specific DA nerve terminal processes will provide insight into how PCBs may interact with other environmental contaminants to alter neurotransmitter function, and ultimately influence behavior.

Accurate identification of fishes is essential for understanding their biology and to ensure food safety for consumers. DNA barcoding is an important tool because it can verify identifications of both whole and processed fishes that have had key morphological characters removed (e.g., filets, fish meal); however, DNA reference libraries are incomplete, and public repositories for sequence data contain incorrectly identified sequences. During a nine-year sampling program in the Philippines, a global biodiversity hotspot for marine fishes, we developed a verified reference library of cytochrome c oxidase subunit I (COI) sequences for 2,525 specimens representing 984 species. Specimens were primarily purchased from markets, with additional diversity collected using rotenone or fishing gear. Species identifications were verified based on taxonomic, phenotypic, and genotypic data, and sequences are associated with voucher specimens, live-color photographs, and genetic samples catalogued at Smithsonian Institution, National Museum of Natural History. The Biodiversity of Philippine Marine Fishes dataset is released herein to increase knowledge of species diversity and distributions and to facilitate accurate identification of market fishes.

From January 21 through February 23, 2020, public health agencies detected 14 U.S. cases of coronavirus disease 2019 (COVID-19), all related to travel from China (1,2). The first nontravel-related U.S. case was confirmed on February 26 in a California resident who had become ill on February 13 (3). Two days later, on February 28, a second nontravel-related case was confirmed in the state of Washington (4,5). Examination of four lines of evidence provides insight into the timing of introduction and early transmission of SARS-CoV-2, the virus that causes COVID-19, into the United States before the detection of these two cases. First, syndromic surveillance based on emergency department records from counties affected early by the pandemic did not show an increase in visits for COVID-19-like illness before February 28. Second, retrospective SARS-CoV-2 testing of approximately 11,000 respiratory specimens from several U.S. locations beginning January 1 identified no positive results before February 20. Third, analysis of viral RNA sequences from early cases suggested that a single lineage of virus imported directly or indirectly from China began circulating in the United States between January 18 and February 9, followed by several SARS-CoV-2 importations from Europe. Finally, the occurrence of three cases, one in a California resident who died on February 6, a second in another resident of the same county who died February 17, and a third in an unidentified passenger or crew member aboard a Pacific cruise ship that left San Francisco on February 11, confirms cryptic circulation of the virus by early February. These data indicate that sustained, community transmission had begun before detection of the first two nontravel-related U.S. cases, likely resulting from the importation of a single lineage of virus from China in late January or early February, followed by several importations from Europe. The widespread emergence of COVID-19 throughout the United States after February highlights the importance of robust public health systems to respond rapidly to emerging infectious threats.