Development of Models for the Prediction of Short-term and Long-term Toxicity to Hyalella azteca from Separate Exposures to Nickel and Cadmium

This study investigated whether principles of the Biotic Ligand Model (BLM), originally developed to predict acute metal toxicity to fish, may be applied to metal accumulation and toxicity in short-term and long-term exposures of Hyalella azteca, an epibenthic invertebrate. In both short-term and long-term exposures, hydrogen and calcium were the only cations found to significantly influence nickel accumulation and toxicity, although some influence by magnesium was suggested in solutions of low calcium and alkalinity. Analysis of short-term (seven-day) bioaccumulation and long-term (28-day) toxicity data established three potential models to explain the observed accumulation and/or toxicity. One of the models included calcium and hydrogen as competitors to nickel (consistent with BLM theory), while the other two models incorporated the non-competitive effect of calcium on the biotic ligand in addition to, or instead of, the competitive action of calcium (not currently considered by BLM theory). Short-term accumulation observed in the tests with adults was best predicted by the competitive (BLM-type) model. However, long-term accumulation and toxicity were predicted equally well by both competitive and non-competitive models. In short-term cadmium exposures the models including calcium as a competitor, rather than an influence on the ligand, predicted accumulation and toxicity best. Hydrogen did not appear to have a significant influence. Although both competitive and non-competitive calcium models were able to predict long-term toxicity within a factor of two of the observed for most tests, the relationship between predicted and observed LC50s was not linear. Instead, for a given calcium concentration, a wide range of LC50s was observed but was associated with a relatively constant predicted LC50 (based on the influence of calcium alone). The predicted LC50s fell roughly in three lateral bands, according to calcium concentrations of approximately 0.3, 1 and 3 mmol/L. The broad range of observed LC50s associated with a relatively constant predicted LC50 reflected variability in organism response in four-week exposures in similar media and/or may have suggested that other factors influencing cadmium toxicity were not accounted for in the models

Ethics Dumping Case Studies from North-South Research Collaborations

This book provides original, up-to-date case studies of “ethics dumping” that were largely facilitated by loopholes in the ethics governance of low and middle-income countries. It is instructive even to experienced researchers since it provides a voice to vulnerable populations from the fore mentioned countries. Ensuring the ethical conduct of North-South collaborations in research is a process fraught with difficulties. The background conditions under which such collaborations take place include extreme differentials in available income and power, as well as a past history of colonialism, while differences in culture can add a new layer of complications. In this context, up-to-date case studies of unethical conduct are essential for research ethics training

Recolonizing carnivores: Is cougar predation behaviorally mediated by bears?

Conservation and management efforts have resulted in population increases and range expansions for some apex predators, potentially changing trophic cascades and foraging behavior. Changes in sympatric carnivore and dominant scavenger populations provide opportunities to assess how carnivores affect one another. Cougars (Puma concolor) were the apex predator in the Great Basin of Nevada, USA, for over 80 years. Black bears (Ursus americanus) have recently recolonized the area and are known to heavily scavenge on cougar kills. To evaluate the impacts of sympatric, recolonizing bears on cougar foraging behavior in the Great Basin, we investigated kill sites of 31 cougars between 2009 and 2017 across a range of bear densities. We modeled the variation in feeding bout duration (number of nights spent feeding on a prey item) and the proportion of primary prey, mule deer (Odocoileus hemionus), in cougar diets using mixed-effects models. We found that feeding bout duration was driven primarily by the size of the prey item being consumed, local bear density, and the presence of dependent kittens. The proportion of mule deer in cougar diet across all study areas declined over time, was lower for male cougars, increased with the presence of dependent kittens, and increased with higher bear densities. In sites with feral horses (Equus ferus), a novel large prey, cougar consumption of feral horses increased over time. Our results suggest that higher bear densities over time may reduce cougar feeding bout durations and influence the prey selection trade-off for cougars when alternative, but more dangerous, large prey are available. Shifts in foraging behavior in multicarnivore systems can have cascading effects on prey selection. This study highlights the importance of measuring the impacts of sympatric apex predators and dominant scavengers on a shared resource base, providing a foundation for monitoring dynamic multipredator/scavenger systems

STEM through Authentic Research and Training Program (START) for Underrepresented Communities: Adapting to the COVID-19 Pandemic

The STEM Through Authentic Research and Training (START) Program is a new program integrating academic, social, and professional experiences, in the theme of exomedicine, to build a pipeline into college for first generation and traditionally underrepresented students by providing year-round authentic opportunities and professional development for high school students and teachers. In response to the COVID-19 pandemic, the START Program has worked with the local Fayette County public school and community partners to provide content to over 300 students through: virtual laboratory tours with community partner Space Tango, meet a scientist discussions, and online near-peer student demonstrations aimed at making the practice of STEM disciplines approachable. Furthermore, the START Program has partnered with Higher Orbits to provide at-home, space-themed learning kits for students to develop teamwork, communication, and STEM principles while engaging in online content with teachers, professionals, and astronauts. Finally, the START Program has moved its training platforms online, including receiving College Reading and Learning Association (CRLA) Peer Educator accreditation for our near-peer mentoring and coaching training. As a result, the START Program is better positioned to address this critical need in STEM education, while reaching more students in the community than possible with face-to-face interactions alone

Human PXR Forms a Tryptophan Zipper-Mediated Homodimer †

The human nuclear receptor pregnane X receptor (PXR) responds to a wide variety of potentially harmful chemicals and coordinates the expression of genes central to xenobiotic and endobiotic metabolism. Structural studies reveal that the PXR ligand binding domain (LBD) uses a novel sequence insert to form a homodimer unique to the nuclear receptor superfamily. Terminal β-strands from each monomeric LBD interact in an ideal antiparallel fashion to bury potentially exposed surface β-strands, generating a ten-stranded intermolecular β-sheet. Conserved tryptophan and tyrosine residues lock across the dimer interface and provide the first tryptophan-zipper (Trp-Zip) interaction observed in a native protein. We show using analytical ultracentrifugation that the PXR LBD forms a homodimer in solution. We further find that removal of the interlocking aromatic residues eliminates dimer formation but does not affect PXR's ability to interact with DNA, RXRα, or ligands. Disruption of the homodimer significantly reduces receptor activity in transient transfection experiments, however, and effectively eliminates the receptor's recruitment of the transcriptional coactivator SRC-1 both in vitro and in vivo. Taken together, these results suggest that the unique Trp-Zip-mediated PXR homodimer plays a role in the function of this nuclear xenobiotic receptor

Navigating Work-Life Integration, Legal Issues, Patient Safety: Lessons for Work-Life Wellness in Academic Medicine: Part 1 of 3

In this series of three manuscripts, we will explore real-life scenarios encountered by clinicians, learners, and researchers in healthcare, which challenge our assumptions and our understanding of how to navigate issues as diverse as mental health, racial diversity, gender discrimination, imposter syndrome, and substance use disorder