Biology subjects

Lee, B. W.

Publications and source records attributed to Lee, B. W..

5 recordsLinked to original sources

bioRxiv2025

Effects of Sodium Glucose Co-Transporter Inhibitors on Work in Human Hypertrophic Cardiomyopathy Living Myocardial Slices

BackgroundDisease modifying therapies for hypertrophic cardiomyopathy (HCM) remain a prevailing unmet need. Human-based experimental platforms capable of controlled manipulation of preload and afterload can distinguish direct myocardial and systemic effects and facilitate development of targeted cardiac therapeutics. Sodium glucose cotransporter inhibitors (SGLTi) may directly affect cardiac contractility, potentially related to increased ketone availability. These effects have not been adequately studied in human HCM myocardium under defined loading conditions. AimsWe sought to establish human living myocardial slices (LMS) as a platform to interrogate load-dependent myocardial mechanics in HCM and to quantify the acute effects of metabolic and pharmacologic interventions--including SGLTi--on myocardial work under physiologic loading conditions. MethodsHuman myocardial tissue was procured from non-failing donor hearts or individuals with HCM undergoing septal myectomy. Freshly prepared human LMS were mechanically tested to generate biomimetic work loops across a range of physiologic preloads and afterloads in either glucose-only fuel or glucose supplemented with ketone. Following baseline measurements, slices were loaded with drug (isoproterenol, mavacamten, sotagliflozin, or empagliflozin) or vehicle (DMSO) and work loop analysis was repeated, allowing each slice to serve as its own control. Mixed effects linear regression models incorporating random effects for heart and slice and fixed effects for clinical characteristics evaluated determinants of myocardial work and drug response across loading conditions. ResultsA total of 120 LMS from 32 individuals (16 non-failing and 16 HCM) were analyzed. At baseline, myocardial work was positively associated with younger age, hypertension, and ejection fraction. Ketone supplementation augmented work and work-strain slope particularly in HCM LMS at high afterloads. We validated our drug testing methodology by demonstrating increased work with known positive inotrope isoproterenol, decreased work with negative inotrope mavacamtem most pronounced in HCM LMS, and a null effect of DMSO. Acute exposure to SGLTi sotagliflozin and empagliflozin directly reduced myocardial work, with increased potency of sotagliflozin at high afterloads. ConclusionsOur LMS platform enables assessment of myocardial mechanics across controlled loading conditions and is an ideal platform to rigorously phenotype human myocardial tissue and interrogate direct effects of pharmacologic intervention. We demonstrate that SGLTi and ketones have distinct and discordant effects on human myocardial contractility.

physiology↗

bioRxiv2023

Identifying drivers of sewage-associated pollutants in pollinators across urban landscapes

Human sewage can introduce pollutants into food webs and threaten ecosystem integrity. Among the many sewage-associated pollutants, pharmaceuticals and personal care products (PPCPs) are useful indicators of sewage in ecosystems and can also cause potent ecological consequences even at minute concentrations (e.g., ng/L). Despite increased study over the past three decades, PPCPs in terrestrial systems have been less studied than those in aquatic ecosystems. To evaluate PPCP prevalence and drivers in a terrestrial ecosystem, we analyzed managed and native bees collected from agroecosystems in Washington State (USA) for PPCPs. Caffeine, paraxanthine, cotinine, and acetaminophen were detected in all three evaluated taxa (Bombus vosnesenskii, Agapostemon texanus, and Apis mellifera), with B. vosnesenskii and A. texanus having a higher probability of PPCP detection relative to A. mellifera. The probability for PPCP presence in all three taxa increased in landscapes with more human development or greater plant abundance, with significant but negative interactions among these factors. These results suggest that human activity, availability of resources, and species-specific traits affect the introduction and mobilization of PPCPs in terrestrial ecosystems. Consequently, monitoring PPCPs and their ecological responses in terrestrial ecosystems creates opportunities to synthesize consequences of sewage pollution across terrestrial and aquatic ecosystems and organism types.

ecology↗

bioRxiv2021

Bee communities in canola are affected by landscape context and farm management

Bees are key pollinators that promote greater yield and seed quality of oilseed crops such as canola. Canola acreage has increased over 1,000% in the past decade in the Pacific Northwest USA, providing a major pulse of sugar-rich nectar and pollen resources that may affect bee health and community structure. However, because canola does not require insect pollination for seed production, few studies have examined the biodiversity of pollinators taking advantage of these resources, or the floral traits of canola that affect pollinators across variable landscapes. Here, we conducted pollinator surveys at canola farms across the inland Northwest region of the USA. We surveyed bee biodiversity and abundance, and assessed how these metrics correlated with landscape context, canola production practices, and floral traits of various canola varieties. We found that bee communities differed between sites and across growing seasons, with sweat bees more abundant later in the season, and mining bees more abundant earlier in the season. We also found that bees were more abundant overall on farms with less floral nectar and with less developed landscape surrounding the sampling area. Bee diversity was greater in spring canola than winter canola, and floral traits were also correlated with differing bee community diversity. This research provides important information for canola growers and land managers and offers a framework for future research in pollinator management in the inland Northwest.

ecology↗

bioRxiv2021

Legume plant defenses and nutrients mediate indirect interactions between soil rhizobia and chewing herbivores

Soil bacteria that form mutualisms with plants, such as rhizobia, affects susceptibility of plants to herbivores and pathogens. Soil rhizobia also promote nitrogen fixation, which mediates host nutrient levels and defenses. However, whether aboveground herbivores affect the function of soil rhizobia remains poorly understood. We assessed reciprocal interactions between Sitona lineatus, a chewing herbivore, and pea (Pisum sativum) plants grown with or without rhizobia (Rhizobium leguminosarum biovar viciae). We also examined the underlying plant-defense and nutritional mechanisms of these interactions. In our experiments, soil rhizobia influenced feeding and herbivory by chewing herbivores. Leaf defoliation by S. lineatus was lower on plants treated with rhizobia, but these insects had similar amino acid levels compared to those on un-inoculated plants. Plants grown with soil rhizobia had increased expression of gene transcripts associated with phytohormone-mediated defense, which may explain decreased susceptibility to S. lineatus. Rhizobia also induced expression of gene transcripts associated with physical and antioxidant-related defense pathways in P. sativum. Conversely, S. lineatus feeding reduced the number of root nodules and nodule biomass, suggesting a disruption of the symbiosis between plants and rhizobia. Our study shows that aboveground herbivores can engage in mutually antagonistic interactions with soil microbes mediated through a multitude of plant-mediated pathways.

ecology↗

bioRxiv2021

Predators affect a plant virus through direct and trait-mediated indirect effects on vectors

Arthropods that vector plant pathogens often interact with predators within food webs. Predators affect vectors by eating them (consumptive effects) and by inducing antipredator behaviors (non-consumptive effects), and these interactions may affect transmission of vector-borne pathogens. However, it has proven difficult to experimentally tease apart the effects of predators on vector fitness and behavior as they are often correlated. We addressed this problem by assessing how both aphids and an aphid-borne pathogen were affected by variable predation risk. Specifically, we experimentally manipulated ladybeetle predators mouthparts to isolate consumptive, and non-consumptive, effects of predators on aphid fitness, movement, and virus transmission. We show that although lethal predators decreased aphid vector abundance, they increased pathogen transmission by increasing aphid movement among hosts. Moreover, aphids responded to risk of predation by moving to younger plant tissue that was more susceptible to the pathogen. Aphids also responded to predator risk through compensatory reproduction, which offset direct consumptive effects. Our results support predictions of disease models showing alterations of vector movement due to predators can have greater effects on transmission of pathogens than vector consumption. Broadly, our study shows isolating direct and indirect predation effects can reveal novel pathways by which predators affect vector-borne pathogens.

ecology↗