Biology subjects

McAdam, A.

Publications and source records attributed to McAdam, A..

4 recordsLinked to original sources

bioRxiv2026

Ankyrin-B regulates cardiomyocyte sarcomere organization and its protein-protein interactions are significantly altered by p.S646F expression

Ankyrin-B (ANKB) is a large (220 kDa) multi-domain membrane-localized cytoplasmic protein that acts as a scaffold coordinating cytoskeletal, ion channel, and transporter proteins critical for proper cardiomyocyte structure and function. There is a prevalence of structural cardiac abnormalities within the cohort of the novel ANKB p.S646F variant that we previously identified in two multigenerational Gitxsan First Nation families, suggesting a role for ANKB in cardiac structure. To investigate the impact of ANKB on cardiomyocyte structural organization, we imaged sarcomere structure in primary cardiomyocytes from cardiac-specific ANKB heterozygous (expressing lower levels of ANKB) and full knock-out mice using confocal microscopy. We observed marked disruption of sarcomere structure in primary cardiac cultures associated with lower ANKB expression, suggesting ANKB is required for proper development of sarcomeres. To shed light on the underlying mechanisms, we next employed an unbiased proteomics approach to identify novel ANKB protein-protein interactions. This analysis uncovered a novel ANKB interaction with -actinin-1, an actin-binding protein that stabilizes focal adhesions essential for development of cardiomyocyte structure. Western blot comparison of -actinin-1 co-precipitation with wildtype ANKB and ANKB p.S646F, revealed increased -actinin-1 enrichment with ANKB p.S646F. Bioinformatics analysis of the ANKB interactome revealed enrichment of cytoskeletal organization, sarcomere structure, and chaperone proteins, and marked changes with ANKB p.S646F. Together findings point to a novel role for ANKB in the regulation of cardiomyocyte structural development and support additional investigation into a link between p.S646F and cardiac structural abnormalities.

cell biology↗

bioRxiv2019

Individual variation in phenotypic plasticity of the stress axis

Phenotypic plasticity--one individuals capacity for phenotypic variation under different environments--is critical for organisms facing fluctuating conditions within their lifetime. North American red squirrels (Tamiasciurus hudsonicus) experience drastic among-year fluctuations in conspecific density. This shapes juvenile competition over vacant territories and overwinter survival. To help young cope with competition at high densities, mothers can increase offspring growth rates via a glucocorticoid-mediated maternal effect. However, this effect is only adaptive under high densities, and faster growth often comes at a cost to longevity. While experiments have demonstrated that red squirrels can adjust hormones in response to fluctuating density, the degree to which mothers differ in their ability to regulate glucocorticoids across changing densities remains unknown--little is known about within-individual plasticity in endocrine traits relative to among-individual variation. Findings from our reaction norm approach revealed significant individual variation not only in a female red squirrels mean endocrine phenotype, but also in endocrine plasticity in response to changes in local density. Future work on the proximate and ultimate drivers of variation in the plasticity of endocrine traits and maternal effects is needed, particularly in free-living animals experiencing fluctuating environments.

zoology↗

bioRxiv2018

Seed masting causes fluctuations in optimum litter size and lag load in a seed predator

The episodic production of large seed crops by some perennial plants, is referred to as masting and is known to increase seed escape by alternately starving and swamping seed predators. These pulses of resources, however, might also act as an agent of selection on the life histories of seed predators, which could indirectly enhance seed escape by inducing an evolutionary load on seed predator populations. Lag loads in seed predators could result from mast-induced shifts in optimum phenotypes that exceed the capacity of seed predators to adaptively track optimum phenotypes through phenotypic plasticity. Alternatively, masting could generate mismatches in selection across generations, where adaptation to the parental environment leads to maladaptation in the offspring environment. Here we measured natural selection on female North American red squirrels (Tamiasciurus hudsonicus) across 28 years and five white spruce (Picea glauca) masting events. Red squirrel litter sizes were similar to optimum litter sizes during non-mast years, but were well below optimum litter sizes during resource-rich mast years. Mast events, therefore caused selection for larger litters ({beta} = 0.25) and a lag load (L = 0.25) on red squirrels during mast years. Furthermore, we found that the annual fitness of spruce trees was negatively related to the local density of squirrels during mast years, indicating that the observed lag load on squirrels enhanced the number of spruce cones escaping squirrel predation. Although, the frequency of mast events and the demography of red squirrels were such that offspring and parents often experienced opposite environments with respect to the mast, we found no effect of environmental mismatches across generations on either offspring survival or population growth. Instead, squirrels plastically increased litter sizes in anticipation of mast events, which partially, although not completely, reduced the lag load resulting from this change in food availability. Variable selection on litter size caused by white spruce mast events, therefore, induced a lag load on the population of red squirrels that was not affected by whether individual squirrels were born during mast (matching) or non-mast (mismatching) conditions.

evolutionary biology↗

bioRxiv2018

Stress activity is not predictive of coping style in North American red squirrels

Individuals vary in their behavioral and physiological responses to environmental changes. These behavioral responses are often described as coping styles along a proactive-reactive continuum. Studies in laboratory populations often, but not always, find that behavioral responses and physiological responses to stressors covary, where more proactive (more aggressive and active) individuals have a lower physiological stress response, specifically as measured by hypothalamic-pituitary-adrenal (HPA) axis activity. These studies support the possibility of hormonal pleiotropy underlying the presentation of behaviors that make up the proactive-reactive phenotype. However, recent research in wild populations is equivocal, with some studies reporting the same pattern as found in many controlled laboratory studies, whereas others do not. We tested the hypothesis that physiological and behavioral stress responses are correlated in wild adult North American red squirrels (Tamiasciurus hudsonicus). We used fecal cortisol metabolites (FCMs) as a non-invasive, integrated estimate of circulating glucocorticoids for our measurement of HPA axis activity. We found that FCM concentrations were not correlated with three measures of behavioral coping styles (activity, aggression, and docility) among individuals. This does not support the hypothesis that hormonal pleiotropy underlies a proactive-reactive continuum of coping styles. Instead, our results support the \"two-tier\" hypothesis that behavioral and physiological stress responses are independent and uncorrelated traits among individuals in wild populations that experience naturally varying environments rather than controlled environments. If also found in other studies, this may alter our predictions about the evolutionary consequences of behavioral and endocrine coping styles in free-living animals.\n\nSignificance StatementIndividuals vary in how they respond to stressors through behavior and physiology, but we find the two responses are independent in wild animals. Many laboratory studies find links between the behavioral and physiological stress responses, however studies conducted with wild populations are less conclusive. In wild North American red squirrels, independence between the physiological response and behavioral response may allow adaptive responses to a changing environment without pleiotropic constraint.

animal behavior and cognition↗