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BackgroundElevated adiposity is often posited by medical and public health researchers to be a risk factor associated with cardiovascular disease, diabetes, and other diseases. These health challenges are now thought to be reflected in epigenetic modifications to DNA molecules, such as DNA methylation, which can alter gene expression.MethodsHere we report the results of three Epigenome Wide Association Studies (EWAS) in which we assessed the differential methylation of DNA (obtained from peripheral blood) associated with three adiposity phenotypes (BMI, waist circumference, and impedance-measured percent body fat) among American Indian adult participants in the Strong Heart Study.ResultsWe found differential methylation at 8264 CpG sites associated with at least one of our three response variables. Of the three adiposity proxies we measured, waist circumference had the highest number of associated differentially methylated CpGs, while percent body fat was associated with the lowest. Because both waist circumference and percent body fat relate to physiology, we focused interpretations on these variables. We found a low degree of overlap between these two variables in our gene ontology enrichment and Differentially Methylated Region analyses, supporting that waist circumference and percent body fat measurements represent biologically distinct concepts.ConclusionsWe interpret these general findings to indicate that highly significant regions of the genome (DMR) and synthesis pathways (GO) in waist circumference analyses are more likely to be associated with the presence of visceral/abdominal fat than more general measures of adiposity. Our findings confirmed numerous CpG sites previously found to be differentially methylated in association with adiposity phenotypes, while we also found new differentially methylated CpG sites and regions not previously identified.

Social environment profoundly influences the fitness of animals, affecting their probability of survival to adulthood, longevity, and reproductive output. The social conditions experienced by parents at the time of reproduction can predict the social environments that offspring will face. Despite clear challenges in predicting future environmental conditions, adaptive maternal effects provide a mechanism of passing environmental information from parent to offspring and are now considered pervasive in natural systems. Maternal effects have been widely studied in vertebrates, especially in the context of social environment, and are often mediated by steroid hormone (SH) deposition to eggs. In insects, although many species dramatically alter phenotype and life‐history traits in response to social density, the mechanisms of these alterations, and the role of hormone deposition by insect mothers into their eggs, remains unknown. In the experiments described here, we assess the effects of social environment on maternal hormone deposition to eggs in house crickets (Acheta domesticus). Specifically, we tested the hypotheses that variable deposition of ecdysteroid hormones (ESH) to eggs is affected by both maternal (a) social density and (b) social composition. We found that while maternal hormone deposition to eggs does not respond to social composition (sex ratio), it does reflect social density; females provision their eggs with higher ESH doses under low‐density conditions. This finding is consistent with the interpretation that variable ESH provisioning is an adaptive maternal response to social environment and congruent with similar patterns of variable maternal provisioning across the tree of life. Moreover, our results confirm that maternal hormone provisioning may mediate delayed density dependence by introducing a time lag in the response of offspring phenotype to population size. Here we show that female crickets respond to social density in provisioning their eggs with hormones that govern hatchling growth and development. This is the first evidence that we are aware of for hormone provisioning as a mechanism for achieving delayed density dependence in a population.

An animal’s phenotype may be shaped by its genes, but also reflects its own environment and often that of its parents. Nongenetic parental effects are often mediated by steroid hormones, and operate between parents and offspring through mechanisms that are well described in vertebrate and non-vertebrate model systems. However, less is understood about the strength and frequency of hormone mediated nongenetic parental effects across more than one generation of descendants, and in nonmodel systems. In Chapter 2, I report that variation in the ecdysteroid hormones (ESH) provided by female house crickets (Acheta domesticus) to their eggs can be robustly, replicably measured using an Enzyme Immunoassay technique. In Chapter 3, I show that variation in the ESH that female A. domesticus deposit into their eggs determines the early development rates of their offspring. I also show that variation in the active forms of ESH provided by a female house cricket to her eggs derives primarily from the quality of nutrition available to her mother and maternal grandmother, regardless of genetic background, age at oviposition, or any contribution of ESH by her mate. In Chapter 4, I uncover a potential mechanism of generating delayed density dependence by showing that female A. domesticus alter their ESH provisioning strategy in response to social density. In Chapter 5, I demonstrate that these effects are not limited to lab-raised species, but are relevant to and present in at least two species of wild Gryllid (Gryllus veletis and G. pennsylvanicus). In sum, work reported here demonstrates the power of variable hormone provisioning by mothers to their offspring. These findings highlight the importance of distinguishing between phenotypic plasticity and genetic effects in observing field and laboratory organisms across time and space.

Wildlife is exposed to a diverse set of extrinsic and intrinsic stressors, such as climatic variation or life history constraints, which may impact individual health and fitness. El Niño and climatic anomalies between 2013 and 2016 had major ecological impacts on the California Current ecosystem. As top marine predators, California sea lions (CSL) experienced decreased prey availability and foraging success, impacting their nutritional state. We hypothesize that chronic stress to juvenile CSL increased during the 2015-2016 El Niño and that breeding represents a period of chronic stress for adults, which impact a variety of physiological processes. We opportunistically captured and sampled juvenile CSL (female,  29; male,  38) in central California and adult male CSL (  76) in Astoria, Oregon and quantified a suite of analytes in serum as indicators of acute stress markers, metabolism and thyroid function, and adaptive immune response. We found that stress hormones and glucose were decreased in juvenile CSL during 2016 relative to 2015 and in adult male CSL after the breeding season, which may indicate chronic stress downregulating HPA (hypothalamic-pituitary-adrenal) axis sensitivity with associated metabolic impacts. Conversely, thyroid hormones for both juvenile and adult male CSL were increased, suggesting greater energetic requirements resulting from increased foraging activity during suboptimal conditions in juveniles and breeding tenure in adult males. Immunoglobulin IgG was elevated in juveniles in 2016 but reduced in adult males post-breeding. This suggests that juveniles may face immunostimulatory pressure during anomalously warm ocean environments; however, for adult males, breeding is a significant energetic cost resulting in reductions to immune function. Our results indicate that environmental conditions and life history stage may influence physiological responses in an important marine predator and a sentinel species of changing ocean ecosystems.

Wildlife is exposed to a diverse set of extrinsic and intrinsic stressors, such as climatic variation or life history constraints, which may impact individual health and fitness. El Nino and climatic anomalies between 2013 and 2016 had major ecological impacts on the California Current ecosystem. As top marine predators, California sea lions (CSL) experienced decreased prey availability and foraging success, impacting their nutritional state. We hypothesize that chronic stress to juvenile CSL increased during the 2015-2016 El Nino and that breeding represents a period of chronic stress for adults, which impact a variety of physiological processes. We opportunistically captured and sampled juvenile CSL (female, n = 29; male, n = 38) in central California and adult male CSL (n = 76) in Astoria, Oregon and quantified a suite of analytes in serum as indicators of acute stress markers, metabolism and thyroid function, and adaptive immune response. We found that stress hormones and glucose were decreased in juvenile CSL during 2016 relative to 2015 and in adult male CSL after the breeding season, which may indicate chronic stress downregulating HPA (hypothalamic-pituitary-adrenal) axis sensitivity with associated metabolic impacts. Conversely, thyroid hormones for both juvenile and adult male CSL were increased, suggesting greater energetic requirements resulting from increased foraging activity during suboptimal conditions in juveniles and breeding tenure in adult males. Immunoglobulin IgG was elevated in juveniles in 2016 but reduced in adult males post-breeding. This suggests that juveniles may face immunostimulatory pressure during anomalously warm ocean environments; however, for adult males, breeding is a significant energetic cost resulting in reductions to immune function. Our results indicate that environmental conditions and life history stage may influence physiological responses in an important marine predator and a sentinel species of changing ocean ecosystems.

Background We studied the safety and efficacy of performing low-risk elective and acute infarct percutaneous coronary interventions at a community hospital without cardiac surgical capability. Methods Immanuel St Joseph's Hospital is located 85 miles from St Mary's Hospital, which is the nearest center with on-site cardiac surgery. All components of the Mayo Clinic percutaneous coronary intervention program were replicated at Immanuel St Joseph's Hospital, including a telemedicine system to enable real-time consultation with interventional and cardiac surgical colleagues during procedures. Results From March 1999 to June 2001, 196 patients underwent elective percutaneous coronary intervention at Immanuel St Joseph's Hospital. Procedural success was achieved in 195 (99.5%) patients, with 1 (0.5%) inhospital death. At mean follow-up of 8.2 months, 2 (1.0%) additional patients died of noncardiac causes and 15 (7.7%) patients required target vessel revascularization. From March 2000 to June 2001, 89 patients underwent primary percutaneous coronary intervention for acute myocardial infarction. Procedural success was achieved in 83 (93.3%) patients, with 3 (3.4%) inhospital deaths. At 30-day follow up, no additional patients died, had recurrent myocardial infarction, or required target vessel revascularization. No patients required transfer to another facility for emergent cardiac surgery for a procedure-related complication. Conclusions Low-risk elective and acute infarct percutaneous coronary interventions can be performed with safety and efficacy at a community hospital without cardiac surgical capability by following rigorous standards. (Am Heart J 2003;145:278-84.)

The actomyosin cortex is an active material that provides animal cells with a strong but flexible exterior, whose mechanics, including non-Gaussian fluctuations and occasional large displacements or cytoquakes, have defied explanation. We study the active fluctuations of the cortex using nanoscale tracking of arrays of flexible microposts adhered to multiple cultured cell types. When the confounding effects of static heterogeneity and tracking error are removed, the fluctuations are found to be heavy-tailed and well-described by a truncated Lévy alpha-stable distribution over a wide range of timescales, in multiple cell types. The largest random displacements closely resemble the earlier-reported cytoquakes, but notably, we find these cytoquakes are not due to earthquake-like cooperative rearrangement of many cytoskeletal elements. Rather, they are indistinguishable from chance large excursions of a super-diffusive random process driven by heavy-tailed noise. The non-cooperative microscopic events driving these fluctuations need not be larger than the expected elastic energy of single tensed cortical actin filaments, and the implied distribution of microscopic event energies will need to be accounted for by future models of the cytoskeleton.

The eight-planet Kepler-90 system exhibits the greatest multiplicity of planets found to date. All eight planets are transiting and were discovered in photometry from the NASA Kepler primary mission. The two outermost planets, g (\\(P_g\\) = 211 d) and h (\\(P_h\\) = 332 d) exhibit significant transit-timing variations (TTVs), but were only observed 6 and 3 times respectively by Kepler. These TTVs allow for the determination of planetary masses through dynamical modeling of the pair's gravitational interactions, but the paucity of transits allows a broad range of solutions for the masses and orbital ephemerides. To determine accurate masses and orbital parameters for planets g and h, we combined 34 radial velocities (RVs) of Kepler-90, collected over a decade, with the Kepler transit data. We jointly modeled the transit times of the outer two planets and the RV time series, then used our two-planet model to predict their future times of transit. These predictions led us to recover a transit of Kepler-90 g with ground-based observatories in May 2024. We then combined the 2024 transit and several previously unpublished transit times of planets g and h with the Kepler photometry and RV data to update the masses and linear ephemerides of the planets, finding masses for g and h of \\(15.0 1.3\\, M_\\), and \\(203 16\\, M_\\) respectively from a Markov Chain Monte Carlo analysis. These results enable further insights into the architecturally rich Kepler-90 system and pave the way for atmospheric characterization with space-based facilities.