Perfluorooctanoic acid induces liver and serum dyslipidemia in humanized PPARα mice fed an American diet.

Per- and polyfluoroalkyl substances (PFAS) are pervasive in the environment resulting in nearly universal detection in people. Human serum PFAS concentrations are strongly associated with increased serum low-density lipoprotein cholesterol (LDL-C), and growing evidence suggests an association with serum triacylglycerides (TG). Here, we tested the hypothesis that perfluorooctanoic acid (PFOA) dysregulates liver and serum triacylglycerides in human peroxisome proliferator activated receptor α (hPPARα)-expressing mice fed an American diet. Mice were exposed to PFOA (3.5 mg/L) in drinking water for 6 weeks resulting in a serum concentration of 48 ± 9 µg/ml. In male and female hPPARα mice, PFOA increased total liver TG and TG substituted with saturated and monounsaturated fatty acids. Lack of expression of PPARα alone also increased total liver TG, and PFOA treatment had little effect on liver TG in PPARα null mice. In hPPARα mice, PFOA neither significantly increased nor decreased serum TG; however, there was a modest increase in TG associated with very low-density cholesterol particles in both sexes. Intriguingly, in female PPARα null mice, PFOA significantly increased serum TG, with a similar trend in males. PFOA also modified fatty acid and TG homeostasis-related gene expression in liver, in a hPPARα-dependent manner, but not in adipose. The results of our study and others reveal the importance of context (serum concentration and genotype) in determining the effect of PFOA on lipid homeostasis.

Use of Fish Telemetry in Rehabilitation Planning, Management, and Monitoring in Areas of Concern in the Laurentian Great Lakes.

Freshwater ecosystems provide many ecosystem services; however, they are often degraded as a result of human activity. To address ecosystem degradation in the Laurentian Great Lakes, Canada and the United States of America established the Great Lakes Water Quality Agreement (GLWQA). In 1987, 43 highly polluted and impacted areas were identified under the GLWQA as having one or more of 14 Beneficial Use Impairments (BUIs) to the physical and chemical habitat for fish, wildlife and humans, and were designated as Areas of Concern (AOC). Subnational jurisdictions combined with local stakeholders, with support from federal governments, developed plans to remediate and restore these sites. Biotelemetry (the tracking of animals using electronic tags) provides information on the spatial ecology of fish in the wild relevant to habitat management and stock assessment. Here, seven case studies are presented where biotelemetry data were directly incorporated within the AOC Remedial Action Plan (RAP) process. Specific applications include determining seasonal fish-habitat associations to inform habitat restoration plans, identifying the distribution of pollutant-indicator species to identify exposure risk to contamination sources, informing the development of fish passage facilities to enable fish to access fragmented upstream habitats, and assessing fish use of created or restored habitats. With growing capacity for fish biotelemetry research in the Great Lakes, we discuss the strengths and weaknesses of incorporating biotelemetry into AOC RAP processes to improve the science and practice of restoration and to facilitate the delisting of AOCs.

Spatial ecology of non-native common carp (Cyprinus carpio) in Lake Ontario with implications for management.

Common carp, Cyprinus carpio, are a non-native species that established within the Laurentian Great Lakes more than a century ago and are abundant in some locations. Common carp have negatively impacted freshwater ecosystems, including in the Great Lakes, by increasing turbidity and uprooting vegetation through foraging and/or spawning activities. Knowledge of spatial ecology is necessary to effectively manage non-native species and aid in the development of remediation strategies. The aim of this study was to examine the spatial ecology of common carp across multiple spatial scales within Lake Ontario using passive acoustic telemetry. First, Residency Index (RI), as a metric for habitat preference, was calculated for common carp in Toronto Harbour (TH) and Hamilton Harbour (HH). Linear mixed modelling revealed that season, as well as the interaction between season and physical habitat conditions significantly affected RI. Specifically, during spring and summer common carp had significantly higher RI at sites with increased submerged aquatic vegetation, which could be associated with spawning activities. All common carp tagged in HH were resident, compared to half of individuals tagged in TH. Larger individuals tagged in TH were more likely to be absent from the array during summer. Non-resident common carp tagged at TH made extensive movements in spring and summer along the nearshore of Lake Ontario and were detected throughout the entire basin. Knowledge of spawning habitat could inform efforts to exclude common carp from these specific locations. Based on our findings, common carp should be managed at a regional level, as opposed to single sites, owing to their extensive movements. Supplementary Information: The online version contains supplementary material available at 10.1007/s00027-022-00917-9.

"These boots were made for walking": the isotopic analysis of a C(4) Roman inhumation from Gravesend, Kent, UK.

As part of the road widening scheme between London and Dover, Oxford Archaeology South uncovered a large boundary ditch of Iron Age origin that contained Iron Age and Roman inhumations, adjacent to which was a small mid-late Roman cemetery, interpreted as a rural cemetery for Romano-British farmers. Grave goods in the cemetery were restricted to a few individuals with hobnailed boots. Bulk bone collagen isotopic analysis of 11 skeletons of Iron Age and Roman date gave a typical C(3) terrestrial signal (average δ(13) C = -19.8‰, δ(15) N = 9.3‰), but also revealed one (SK12671) with a diet which included a substantial C(4) component (δ(13) C = -15.2‰, δ(15) N = 11.2‰). This is only the second such diet reported in Roman Britain. Subsequent δ(18) O(c) and (87) Sr/(86) Sr measurements on the dental enamel in this individual were, however, consistent with a "local" origin, indicating that either C(4) protein was consumed in Late Roman Britain, or that he came from somewhere else, but where conditions gave rise to similar isotopic values. If we accept the latter, then it indicates that using oxygen and strontium isotopes alone to identify "incomers" may be problematic. The provision of hobnailed boots for the dead appears to have had a strong symbolic element in Late Roman Britain. We suggest that in this case the boots may be significant, in that he was being equipped for the long march home.

Blocking extracellular activation of myostatin as a strategy for treating muscle wasting.

Many growth factors are intimately bound to the extracellular matrix, with regulated processing and release leading to cellular stimulation. Myostatin and GDF11 are closely related members of the TGFß family whose activation requires two proteolytic cleavages to release the growth factor from the prodomain. Specific modulation of myostatin and GDF11 activity by targeting growth factor-receptor interactions has traditionally been challenging. Here we demonstrate that a novel strategy for blocking myostatin and GDF11, inhibition of growth factor release, specifically and potently inhibits signaling both in vitro and in vivo. We developed human monoclonal antibodies that selectively bind the myostatin and GDF11 precursor forms, including a subset that inhibit myostatin proteolytic activation and prevent muscle atrophy in vivo. The most potent myostatin activation-blocking antibodies promoted robust muscle growth and resulted in significant gains in muscle performance in healthy mice. Altogether, we show that blocking the extracellular activation of growth factors is a potent method for preventing signaling, serving as proof of concept for a novel therapeutic strategy that can be applied to other members of the TGFß family of growth factors.

Manipulation of Ovarian Function Significantly Influenced Trabecular and Cortical Bone Volume, Architecture and Density in Mice at Death.

Previously, transplantation of ovaries from young, cycling mice into old, postreproductive-age mice increased life span and decreased cardiomyopathy at death. We anticipated that the same factors that increased life span and decreased cardiomyopathy could also influence the progression of orthopedic disease. At 11 months of age, prepubertally ovariectomized and ovary-intact mice (including reproductively cycling and acyclic mice) received new 60-day-old ovaries. At death, epiphyseal bone in the proximal tibia and the distal femur and mid-shaft tibial and femoral diaphyseal bone was analyzed with micro-computed tomography. For qualitative analysis of osteophytosis, we also included mineralized connective tissue within the stifle joint. Prepubertal ovariectomy had the greatest influence on bone volume, ovarian transplantation had the greatest influence on bone architecture and both treatments influenced bone density. Ovarian transplantation increased cortical, but not trabecular bone density and tended to increase osteophytosis and heterotopic mineralization, except in acyclic recipients. These effects may have been dictated by the timing of the treatments, with ovariectomy appearing to influence early development and ovarian transplantation limited to influencing only the postreproductive period. However, major differences observed between cycling, acyclic and ovariectomized recipients of new ovaries may have been, in part due to differences in the levels of hormone receptors present and the responsiveness of specific bone processes to hormone signaling. Changes that resulted from these treatments may represent a compensatory response to normal age-associated, negative, orthopedic changes. Alternatively, differences between treatments may simply be the 'preservation' of unblemished orthopedic conditions, prior to the influence of negative, age-associated effects. These findings may suggest that in women, tailoring hormone replacement therapy to the patient's current reproductive status may improve therapy effectiveness and that beginning therapy earlier may help preserve trabecular bone mineral density that would otherwise be lost during perimenopause.

Effect of pretreatment with 3-methylcholanthrene and several phenolic antioxidants on glutathione S-transferase activity in various tissues of female Sprague-Dawley rats.

1. Treatment of female Sprague-Dawley rats with 3-methylcholanthrene, butylated hydroxyanisole, ethoxyquin, propyl gallate or methylcholanthrene plus butylated hydroxyanisole was undertaken to determine the effects on glutathione S-transferase activity in liver, small intestine, lung and kidney. 2. A significant increase in hepatic transferase activity was found following all treatments, except after propyl gallate, when 1-chloro-2,4-dinitrobenzene was used as substrate. 3. When 1,2-dichloro-4-nitrobenzene was the substrate, only butylated hydroxyanisole and the combination of butylated hydroxyanisole and methylcholanthrene resulted in a significant increase. 4. In the extra-hepatic tissues using 1-chloro-2,4-dinitrobenzene as a substrate, all treatments caused an increase in transferase activity in the lung; ethoxyquin and combined methylcholanthrene plus butylated hydroxyanisole increased this activity in the kidney, whereas only the combined methylcholanthrene plus butylated hydroxyanisole increased activity in the small intestine. 5. All treatments caused a notable decrease in the composite Km and had varying effects on the composite Vmax of hepatic transferase activity.

The Tri Council for Nursing: 15 years of fruitful cooperation.

Although not a decision making body, the Tri Council for nursing has provided a forum for cooperation among the major nursing organizations. It has also served as a voice for the profession in addressing policymakers, legislators, and the general public.