Assaying Environmental Nickel Toxicity Using Model Nematodes

Although nickel exposure results in allergic reactions, respiratory conditions, and cancer in humans and rodents, the ramifications of excess nickel in the environment for animal and human health remain largely undescribed. Nickel and other cationic metals travel through waterways and bind to soils and sediments. To evaluate the potential toxic effects of nickel at environmental contaminant levels (8.9-7,600 µg Ni/g dry weight of sediment and 50-800 µg NiCl2/L of water), we conducted assays using two cosmopolitan nematodes, Caenorhabditis elegans and Pristionchus pacificus. We assayed the effects of both sediment-bound and aqueous nickel upon animal growth, developmental survival, lifespan, and fecundity. Uncontaminated sediments were collected from sites in the Midwestern United States and spiked with a range of nickel concentrations. We found that nickel-spiked sediment substantially impairs both survival from larval to adult stages and adult longevity in a concentration-dependent manner. Further, while aqueous nickel showed no adverse effects on either survivorship or longevity, we observed a significant decrease in fecundity, indicating that aqueous nickel could have a negative impact on nematode physiology. Intriguingly, C. elegans and P. pacificus exhibit similar, but not identical, responses to nickel exposure. Moreover, P. pacificus could be tested successfully in sediments inhospitable to C. elegans. Our results add to a growing body of literature documenting the impact of nickel on animal physiology, and suggest that environmental toxicological studies could gain an advantage by widening their repertoire of nematode species

Sequencing and timing of strategic responses after industry disruption: evidence from post-deregulation competition in the U.S. railroad industry

This paper examines the sequencing and timing of firms’ strategic responses after significant industry disruption. We show that it is not the single strategic choice or response per se, but the sequencing and patterns of consecutive strategic responses that drive a firm’s adaptation and survival in the aftermath of a shift in the industry. We find that firms’ renewal efforts involved differential adaptability in finding balance at the juxtaposition of responding to demand-side pressures and choosing a path of new capability acquisition efficiently. Our study underscores the importance of taking a sequencing approach to studying strategic responses to industry disruption

Virtual Partner Interaction (VPI): Exploring Novel Behaviors via Coordination Dynamics

Inspired by the dynamic clamp of cellular neuroscience, this paper introduces VPI—Virtual Partner Interaction—a coupled dynamical system for studying real time interaction between a human and a machine. In this proof of concept study, human subjects coordinate hand movements with a virtual partner, an avatar of a hand whose movements are driven by a computerized version of the Haken-Kelso-Bunz (HKB) equations that have been shown to govern basic forms of human coordination. As a surrogate system for human social coordination, VPI allows one to examine regions of the parameter space not typically explored during live interactions. A number of novel behaviors never previously observed are uncovered and accounted for. Having its basis in an empirically derived theory of human coordination, VPI offers a principled approach to human-machine interaction and opens up new ways to understand how humans interact with human-like machines including identification of underlying neural mechanisms

CNS Infiltration of Peripheral Immune Cells: D-Day for Neurodegenerative Disease?

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as “immune privilege,” it is now clear that immune responses do occur in the CNS—giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue

Effect of a hypertonic balanced ketone solution on plasma, CSF and brain beta-hydroxybutyrate levels and acid-base status

Purpose: Although glucose is the main source of energy for the human brain, ketones play an important role during starvation or injury. The purpose of our study was to investigate the metabolic effects of a novel hypertonic sodium ketone solution in normal animals. Methods: Adult Sprague-Dawley rats (420-570 g) were divided into three groups of five, one control and two study arms. The control group received an intravenous infusion of 3 % NaCl at 5 ml/kg/h. The animals in the two study arms were assigned to receive one of the two formulations of ketone solutions, containing hypertonic saline with 40 and 120 mmol/l beta-hydroxybutyrate, respectively. This was infused for 6 h and then the animal was euthanized and brains removed and frozen. Results: Both blood and cerebrospinal fluid (CSF) levels of beta-hydroxybutyrate (BHB) demonstrated strong evidence of a change over time (p < 0.0001). There was also strong evidence of a difference between groups (p < 0.0001). Multiple comparisons showed all these means were statistically different (p < 0.05). Measurement of BHB levels in brain tissue found strong evidence of a difference between groups (p < 0.0001) with control: 0.15 mmol/l (0.01), BHB 40: 0.19 mmol/l (0.01), and BHB 120: 0.28 mmol/l (0.01). Multiple comparisons showed all these means were statistically different (p < 0.05). There were no differences over time (p = 0.31) or between groups (p = 0.33) or an interaction between groups and time (p = 0.47) for base excess. Conclusion: The IV infusions of hypertonic saline/BHB are feasible and lead to increased plasma, CSF and brain levels of BHB without significant acid/base effects