Comparative spatially explicit approach for testing effects of soil chemicals on terrestrial wildlife bioindicator demographics.

Wildlife species are often used as bioindicators to evaluate the extent and severity of environmental contamination and the effectiveness of remediation practices. A common approach for investigating population- or community-level impacts on bioindicators compares demographic parameter estimates (e.g., population size or density) between sites that were subjected to different levels of contamination. However, the traditional analytical method used in such studies is nonspatial capture-recapture, which results in conclusions about potential relationships between demographics and contaminants being inferred indirectly. Here, we extend this comparative approach to the spatially explicit framework, allowing direct estimation of said relationships and comparisons between study areas, by applying spatial capture-recapture (SCR) models to bioindicator (deer mice [Peromyscus spp.]) detection data from two study areas that were subjected to different industrial activities and remediation practices. Bioindicator density differed by 178% between the neighboring study areas, and the area with the highest soil concentrations of polychlorinated biphenyls, chromium, and zinc had the highest bioindicator density. Under the traditional nonspatial approach, we might have concluded that soil chemical levels had negligible influences on demographics. However, by modeling density as a spatial function of select chemical concentrations using SCR models, we found strong support for a positive relationship between density and soil chromium concentrations in one study area (ß = 0.82), which was not masked by or associated with habitat-related metrics. To obtain reliable inferences about potential effects of environmental contamination on bioindicator demographics, we contend that a comparative spatially explicit approach using SCR ought to become standard.

Investigating effects of soil chemicals on density of small mammal bioindicators using spatial capture-recapture models.

Monitoring the ecological impacts of environmental pollution and the effectiveness of remediation efforts requires identifying relationships between contaminants and the disruption of biological processes in populations, communities, or ecosystems. Wildlife are useful bioindicators, but traditional comparative experimental approaches rely on a staunch and typically unverifiable assumption that, in the absence of contaminants, reference and contaminated sites would support the same densities of bioindicators, thereby inferring direct causation from indirect data. We demonstrate the utility of spatial capture-recapture (SCR) models for overcoming these issues, testing if community density of common small mammal bioindicators was directly influenced by soil chemical concentrations. By modeling density as an inhomogeneous Poisson point process, we found evidence for an inverse spatial relationship between Peromyscus density and soil mercury concentrations, but not other chemicals, such as polychlorinated biphenyls, at a site formerly occupied by a nuclear reactor. Although the coefficient point estimate supported Peromyscus density being lower where mercury concentrations were higher (ß = -0.44), the 95% confidence interval overlapped zero, suggesting no effect was also compatible with our data. Estimated density from the most parsimonious model (2.88 mice/ha; 95% CI = 1.63-5.08), which did not support a density-chemical relationship, was within the range of reported densities for Peromyscus that did not inhabit contaminated sites elsewhere. Environmental pollution remains a global threat to biodiversity and ecosystem and human health, and our study provides an illustrative example of the utility of SCR models for investigating the effects that chemicals may have on wildlife bioindicator populations and communities.

Escherichia coli, Salmonella, and Mycobacterium avium subsp. paratuberculosis in wild European starlings at a Kansas cattle feedlot.

The prevalence of Escherichia coli, Salmonella spp., and Mycobacterium avium subsp. paratuberculosis isolated from the feces of wild European starlings (Sturnus vulgaris) humanely trapped at a feedlot in central Kansas was assessed. All E. coli and Salmonella isolates recovered were tested for antimicrobial susceptibility using National Antimicrobial Resistance Monitoring System panels and the E. coli isolates were classified as to their content of genes associated with pathogenic E. coli of birds and cattle, including cvaC, iroN2, ompTp, hlyF2, eitC, iss, iutA, ireA, papC, stxI, stxII, sta, K99, F41, and eae. Escherichia coli O157:H7 and Mycobacterium avium subsp. paratuberculosis were not detected and Salmonella was isolated from only three samples, two of which displayed antimicrobial resistance. Approximately half of the E. coli isolates were resistant to antimicrobial agents with 96% showing resistance to tetracycline. Only one isolate was positive for a single gene associated with bovine pathogenic E. coli. An interesting finding of this study was that 5% of the E. coli isolates tested met the criteria established for identification as avian pathogenic E. coli (APEC). Thus these findings suggest that starlings are not a significant source of Salmonella spp., Mycobacterium avium subsp. paratuberculosis, E. coli O157, or other shiga toxin-producing E. coli in this feedlot. However, they may have the potential to spread APEC, an important pathogen of poultry and a potential pathogen to human beings.

Sexual selection constrains the body mass of male but not female mice.

Sexual size dimorphism results when female and male body size is influenced differently by natural and sexual selection. Typically, in polygynous species larger male body size is thought to be favored in competition for mates and constraints on maximal body size are due to countervailing natural selection on either sex; however, it has been postulated that sexual selection itself may result in stabilizing selection at an optimal mass. Here we test this hypothesis by retrospectively assessing the influence of body mass, one metric of body size, on the fitness of 113 wild-derived house mice (Mus musculus) residing within ten replicate semi-natural enclosures from previous studies conducted by our laboratory. Enclosures possess similar levels of sexual selection, but relaxed natural selection, relative to natural systems. Heavier females produced more offspring, while males of intermediate mass had the highest fitness. Female results suggest that some aspect of natural selection, absent from enclosures, acts to decrease their body mass, while the upper and lower boundaries of male mass are constrained by sexual selection.

Rofecoxib-Induced Deleterious Effects Escape Detection by Organismal Performance Assays.

BACKGROUND: Organismal Performance Assays (OPAs) are a unique toxicity quantification method used to assess the safety of potentially toxic compounds, such as pharmaceuticals. OPAs utilize genetically diverse wild mice (Mus musculus) housed in semi-natural enclosures wherein exposed individuals compete directly with controls for resources. Previously, OPAs have been successful in detecting adverse effects in mice that were exposed to paroxetine. Here, we further test OPAs utility in pharmaceutical safety assessment by testing OPAs with rofecoxib, a drug with known adverse effects in humans. METHODS: We exposed mice to rofecoxib (~37.5 mg/kg/day) during gestation and into early adulthood. Exposure ceased when individuals were released into enclosures. Five independent populations were established and rofecoxib-exposed individuals (n = 58) competed directly with control individuals (n = 58) over 28 weeks. Organismal performance was determined by quantifying reproduction, survival and male competitive ability. RESULTS: In enclosures, rofecoxib-exposed males had equal reproduction, survival and competitive ability. Rofecoxib-exposed females had equal survival compared to controls but experienced 40% higher reproductive output. CONCLUSIONS: The adverse health effects of rofecoxib seen in humans escaped detection by OPAs, just as they had during traditional preclinical assays. These results may be explained by the exposure design (in enclosures, all animals were on the control diet), the relatively short duration of exposure, species differences, or because the health benefits of the drug negated the side effects. Similarly to numerous assays used in preclinical trials, OPAs cannot reveal all maladies, despite their demonstrated sensitivity in detecting cryptic toxicity from numerous exposures.

Quantification of cerivastatin toxicity supports organismal performance assays as an effective tool during pharmaceutical safety assessment.

A major problem in pharmaceutical development is that adverse effects remain undetected during preclinical and clinical trials, but are later revealed after market release when prescribed to many patients. We have developed a fitness assay known as the organismal performance assay (OPA), which evaluates individual performance by utilizing outbred wild mice (Mus musculus) that are assigned to an exposed or control group, which compete against each other for resources within semi-natural enclosures. Performance measurements included reproductive success, survival, and male competitive ability. Our aim was to utilize cerivastatin (Baycol(®), Bayer), a pharmaceutical with known adverse effects, as a positive control to assess OPAs as a potential tool for evaluating the safety of compounds during preclinical trials. Mice were exposed to cerivastatin (~4.5 mg/kg/day) into early adulthood. Exposure ceased and animals were released into semi-natural enclosures. Within enclosures, cerivastatin-exposed females had 25% fewer offspring and cerivastatin-exposed males had 10% less body mass, occupied 63% fewer territories, sired 41% fewer offspring, and experienced a threefold increase in mortality when compared to controls. OPAs detected several cerivastatin-induced adverse effects indicating that fitness assays, commonly used in ecology and evolutionary biology, could be useful as an additional tool in safety testing during pharmaceutical development.

Low-dose paroxetine exposure causes lifetime declines in male mouse body weight, reproduction and competitive ability as measured by the novel organismal performance assay.

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that is currently available on the market and is suspected of causing congenital malformations in babies born to mothers who take the drug during the first trimester of pregnancy. We utilized organismal performance assays (OPAs), a novel toxicity assessment method, to assess the safety of paroxetine during pregnancy in a rodent model. OPAs utilize genetically diverse wild mice (Mus musculus) to evaluate competitive performance between experimental and control animals as they compete among each other for limited resources in semi-natural enclosures. Performance measures included reproductive success, male competitive ability and survivorship. Paroxetine-exposed males weighed 13% less, had 44% fewer offspring, dominated 53% fewer territories and experienced a 2.5-fold increased trend in mortality, when compared with controls. Paroxetine-exposed females had 65% fewer offspring early in the study, but rebounded at later time points, presumably, because they were no longer exposed to paroxetine. In cages, paroxetine-exposed breeders took 2.3 times longer to produce their first litter and pups of both sexes experienced reduced weight when compared with controls. Low-dose paroxetine-induced health declines detected in this study that were undetected in preclinical trials with doses 2.5-8 times higher than human therapeutic doses. These data indicate that OPAs detect phenotypic adversity and provide unique information that could be useful towards safety testing during pharmaceutical development.