Phylogenetic signal in amphibian sensitivity to copper sulfate relative to experimental temperature

The release of large quantities of chemicals into the environment represents a major source of environmental disturbance. In recent years, the focus of ecotoxicology has shifted from describing the effects of chemical contaminants on individual species to developing more integrated approaches for predicting and evaluating long term effects of chemicals across species and ecosystems. Traditional ecotoxicology is typically based on data of sensitivity of a few surrogate species to a contaminant and often considers little variability in chemical sensitivity within and among taxonomic groups. This approach assumes that evolutionary history and phylogenetic relatedness among species have little or no impact on species’ sensitivity to chemical compounds. Few studies have tested this assumption. Using phylogenetic comparative methods and published data for amphibians, we show that sensitivity to copper sulfate, a commonly used pesticide, exhibits a strong phylogenetic signal when controlling for experimental temperature. Our results indicate that evolutionary history needs to be accounted for to make accurate predictions of amphibian sensitivity to this contaminant under different temperature scenarios. Since physiological and metabolic traits showing high phylogenetic signal likely underlie variation in species sensitivity to chemical stressors, future studies should evaluate and predict species vulnerability to pollutants using evolutionarily informed approaches

Intra- and interspecific toxicity testing methods and data for nematodes exposed to metals

Twenty-four hour median lethal concentration (LC50) toxicity tests were performed with five species of nematodes (Caenorhabditis elegans, Caenorhabditis briggsae, Pristionchus pacificus, Oscheius tipulae, and Oscheius myriophila) in response to copper chloride and zinc chloride. In addition, lethality tests were also performed with seven strains of C. elegans (N2 &gt; 1 year in culture, N2 newly acquired, N2 ancestral, ED3053, JU258, JU1171, and MY1) exposed to copper chloride. Nominal chemical concentrations were validated and analyzed according to U.S. Environmental Protection Agency method 6010 using inductively coupled plasma–atomic emission spectroscopy (ICP-AES). This paper combines the datasets previously published separately by Heaton et al. (2020, 2022). The goal is to catalog all raw and analyzed toxicity data collected from both studies in a single consistent information source for use by the scientific community.</p

Chemical prioritization of pharmaceuticals and personal care products in an urban tributary of the Potomac River

Pharmaceuticals and personal care products (PPCPs) are incredibly diverse in terms of chemical structures, physicochemical properties, and modes of action, making their environmental impacts challenging to assess. New chemical prioritization methodologies have emerged that compare contaminant monitoring concentrations to multiple toxicity data sources, including whole organism and high-throughput data, to develop a list of “high priority” chemicals requiring further study. We applied such an approach to assess PPCPs in Hunting Creek, an urban tributary of the Potomac River near Washington, DC, which has experienced extensive human population growth. We estimated potential risks of 99 PPCPs from surface water and sediment collected upstream and downstream of a major wastewater treatment plant (WWTP), nearby combined sewer overflows (CSO), and in the adjacent Potomac River. The greatest potential risks to the aquatic ecosystem occurred near WWTP and CSO outfalls, but risk levels rapidly dropped below thresholds of concern – established by previous chemical prioritization studies – in the Potomac mainstem. These results suggest that urban tributaries, rather than larger rivers, are important to monitor because their lower or intermittent flow may not adequately dilute contaminants of concern. Common psychotropics, such as fluoxetine and venlafaxine, presented the highest potential risks, with toxicity quotients often &gt; 10 in surface water and &gt; 1000 in sediment, indicating the need for further field studies. Several ubiquitous chemicals such as caffeine and carbamazepine also exceeded thresholds of concern throughout our study area and point to specific neurotoxic and endocrine modes of action that warrant further investigation. Since many “high priority” chemicals in our analysis have also triggered concerns in other areas around the world, better coordination is needed among environmental monitoring programs to improve global chemical prioritization efforts.</p

Role of denosumab in the management of skeletal complications in patients with bone metastases from solid tumors

Skeletal-related events (SREs) including pain, fractures, and hypercalcemia are a major source of morbidity for cancer patients with bone metastases. The receptor activator of NF-κB ligand (RANKL) is a key mediator of osteoclast formation and activity in normal bone physiology as well as cancer-induced bone resorption. The first commercially available drug that specifically targets and inhibits the RANKL pathway is denosumab, a fully human monoclonal antibody that binds and neutralizes RANKL, thereby inhibiting osteoclast function. In this review, we summarize the major studies leading to the US Food and Drug Administration-approval of denosumab for the prevention of SREs in patients with bone metastases from solid tumors. Further, we discuss the role of denosumab in the prevention and treatment of SREs and bone loss in cancer patients. As a monoclonal antibody, denosumab has several advantages over bisphosphonates, including improved efficacy, better tolerability, and the convenience of administration by subcutaneous injection. In addition, as denosumab has no known renal toxicity, it may be the preferred choice over bisphosphonates in patients with baseline renal insufficiency or receiving nephrotoxic therapies. However, other toxicities, including osteonecrosis of the jaw and hypocalcemia, appear to be class effects of agents that potently inhibit osteoclast activity and are associated with both denosumab and bisphosphonate use. The data presented highlight the differences associated with intravenous bisphosphonate and denosumab use as well as confirm the essential role bone-modifying agents play in maintaining the quality of life for patients with bone metastases

A new revolutionary practice: operaisti and the 'refusal of work' in 1970's Italy

The social protest that engulfed Italy in the 1970s found a theoretical analysis in the work of the operaisti. Through a series of concepts, they outlined a new revolutionary practice that aimed to return to a more authentic reading of Marxism. This article focuses on the notion of ‘refusal of work’ and the ancillary concept of ‘appropriation’ and examines how these theoretical tools emerged out of radical protest in factories and were put forward by the operaisti as a central plank of a revolutionary strategy for the working clas

Physical acting training as therapy : outcomes from three therapeutic physical acting training workshops

The subject area of this research is the therapeutic implication of physical theatre training on a client's journey towards living in accordance with their internal judgment and motivations. The purpose of this study was to determine how healthy adults without a previous history of mental illness respond to brief physical acting training workshops. The intention was to see if the workshop participants experience an increase in their internal locus of control and attention regulation abilities. In this research paper, eight participants' experiences of physical theatre training techniques are described and analyzed. The workshops succeeded in helping the participants heighten their physical and emotional awareness in relation to their internal and external awareness of their environments and interpersonal relationships. The participants also learned about ways in which reactions and actions affect the way they interact with others and how they feel about themselves, helping them realize they have the power to choose what they focus on in their live

The effects of historical fragmentation on major histocompatibility complex class II β and microsatellite variation in the Aegean island reptile, Podarcis erhardii

The major histocompatibility complex (MHC) plays a key role in disease resistance and is the most polymorphic gene region in vertebrates. Although habitat fragmentation is predicted to lead to a loss in MHC variation through drift, the impact of other evolutionary forces may counter this effect. Here we assess the impact of selection, drift, migration, and recombination on MHC class II and microsatellite variability in 14 island populations of the Aegean wall lizard Podarcis erhardii. Lizards were sampled from islands within the Cyclades (Greece) formed by rising sea levels as the last glacial maximum approximately 20,000 before present. Bathymetric data were used to determine the area and age of each island, allowing us to infer the corresponding magnitude and timing of genetic bottlenecks associated with island formation. Both MHC and microsatellite variation were positively associated with island area, supporting the hypothesis that drift governs neutral and adaptive variation in this system. However, MHC but not microsatellite variability declined significantly with island age. This discrepancy is likely due to the fact that microsatellites attain mutation-drift equilibrium more rapidly than MHC. Although we detected signals of balancing selection, recombination and migration, the effects of these evolutionary processes appeared negligible relative to drift. This study demonstrates how land bridge islands can provide novel insights into the impact of historical fragmentation on genetic diversity as well as help disentangle the effects of different evolutionary forces on neutral and adaptive diversity

Concurrent Evolution of Antiaging Gene Duplications and Cellular Phenotypes in Long-Lived Turtles

There are many costs associated with increased body size and longevity in animals, including the accumulation of genotoxic and cytotoxic damage that comes with having more cells and living longer. Yet, some species have overcome these barriers and have evolved remarkably large body sizes and long lifespans, sometimes within a narrow window of evolutionary time. Here, we demonstrate through phylogenetic comparative analysis that multiple turtle lineages, including Galapagos giant tortoises, concurrently evolved large bodies, long lifespans, and reduced cancer risk. We also show through comparative genomic analysis that Galapagos giant tortoises have gene duplications related to longevity and tumor suppression. To examine the molecular basis underlying increased body size and lifespan in turtles, we treated cell lines from multiple species, including Galapagos giant tortoises, with drugs that induce different types of cytotoxic stress. Our results indicate that turtle cells, in general, are resistant to oxidative stress related to aging, whereas Galapagos giant tortoise cells, specifically, are sensitive to endoplasmic reticulum stress, which may give this species an ability to mitigate the effects of cellular stress associated with increased body size and longevity.</p

Priority screening of contaminants of emerging concern (CECs) in surface water:Comparing cell-based bioassays and exposure-activity ratios (EARs)

In this study, we compared a wide range of cell-based bioassays to the use of chemical analysis followed by exposure-activity ratio (EAR) and Toxicological Prioritization index (ToxPi) for prioritizing chemicals, sites, and hazard concerns in water samples. Surface water samples were collected from nine sites in three Central Pennsylvania streams and analyzed for a forty-six contaminants of emerging concern (CECs), including pesticides, personal care products, and pharmaceuticals. Cell-based reporter assays evaluated human and zebrafish molecular initiating events (MIEs) in endocrine and metabolic disruption, altered lipid metabolism, and oxidative stress. Bioassays showed that 12 out of 40 assays had at least one site with activity over the effect-based trigger (EBT) values. The receptors that exhibited the highest number of samples above the EBT that would be expected to cause toxicity were Aryl hydrocarbon receptor (AhR, human and zebrafish), Pregnane X Receptor (PXR), Estrogen Receptor-beta (ERB), and Androgen Receptor (AR). Characterizing the collection sites by their bioactivity aligned closely with the stream in which samples were collected. The sum of all EARs for each chemical indicated that the pharmaceutical Carbamazepine and the pesticides Carbaryl and Atrazine posed the greatest concern. However, predicted activity and site prioritization based on individual chemical analysis and calculated EAR were different than those measured by bioassay, indicating that biologically active chemicals are present in the samples that were not included in the targeted analytes. Taken together, these data show that chemical analysis and EAR analysis are beneficial for prioritization of chemicals, whereas mechanism-based bioassays are more inclusive of known as well as unknown chemical contaminants and thus of more use for overall water quality analysis and site prioritization.</p