Publications by authors named "Stephanie N Kennedy"

Caspase-11 is an innate immune pattern recognition receptor (PRR) that detects cytosolic bacterial lipopolysaccharides (LPS) through its caspase activation and recruitment domain (CARD), triggering inflammatory cell death known as pyroptosis. Caspase-11 also detects eukaryotic ( self) lipids. This observation raises the question of whether common or distinct mechanisms govern the interactions with self and nonself lipids.

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Defective host defenses later in life are associated with changes in immune cell activities, suggesting that age-specific considerations are needed in immunotherapy approaches. In this study, we found that PD-1 and CTLA4-based cancer immunotherapies are unable to eradicate tumors in elderly mice. This defect in anti-tumor activity correlated with two known age-associated immune defects: diminished abundance of systemic naive CD8 T cells and weak migratory activities of dendritic cells (DCs).

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The mechanisms by which innate immune receptors mediate self-nonself discrimination are unclear. In this study, we found species-specific molecular determinants of self-DNA reactivity by cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase (cGAS). Human cGAS contained a catalytic domain that was intrinsically self-DNA reactive and stimulated interferon responses in diverse cell types.

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The Steller sea lion (SSL) population west of 144°W longitude experienced a significant population decline. While there appears to be a stable or increasing population trend in rookeries in the Gulf of Alaska (GOA) and Southeast Alaska (SEA), some rookeries within the Aleutian Islands (AI) have failed to recover. Previous studies found regional differences in whole blood total mercury concentrations ([THg]) showing more than 20% of AI pups had [THg] above critical thresholds for increased risk of immunological effects and other adverse outcomes.

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Selenium (Se) bioavailability is required for synthesis and function of essential Se-dependent antioxidants, including the enzyme glutathione peroxidase (GPx). Strong interactions between monomethyl mercury and Se impair the critical antioxidant role of Se. Approximately 20% of Steller sea lion (Eumetopias jubatus, SSL) pups sampled in the western Aleutian Islands, Alaska, had total Hg concentrations ([THg]) measured in hair and whole blood above thresholds of concern for adverse physiologic effects in pinnipeds.

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Immunoglobulins (Ig) are proteins that preserve immune homeostasis and are quantified to infer changes to the acquired humoral immune response in mammals. Measuring Ig in non-model wildlife for immune surveillance often requires ingenuity, and rigorous standardization of methodologies to provide reliable results especially when lacking species-specific reagents. We modified and optimized existing ELISA methodology utilizing the binding properties of Staphylococcus-derived Protein A (PrtA) to immunoglobulin G (IgG).

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Varying concentrations of the highly conserved acute phase response protein, haptoglobin, can indicate changes to the health and disease status of mammals, including the Steller sea lion (SSL; Eumetopias jubatus). To better understand factors relating to acute phase response in SSLs, circulating haptoglobin concentrations (Hp) were quantified in plasma collected from 1,272 individuals sampled near rookeries and haulouts off the coast of Alaska, US. We compared Hp in SSLs between sexes and among different age classes (young pups, young-of-the-year, yearlings, subadults, and adults) sampled within distinct regions in Alaska (Aleutian Islands, Gulf of Alaska, Southeast Alaska).

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Mercury (Hg) biomonitoring of pinnipeds increasingly utilizes nonlethally collected tissues such as hair and blood. The relationship between total Hg concentrations ([THg]) in these tissues is not well understood for marine mammals, but it can be important for interpretation of tissue concentrations with respect to ecotoxicology and biomonitoring. We examined [THg] in blood and hair in multiple age classes of four pinniped species.

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