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Herron, E.

Publications and source records attributed to Herron, E..

2 recordsLinked to original sources

Aging changes the underlying mechanism of JAK2 modulation in neutrophil function

Janus Kinase 2 (JAK2) has been linked to various neutrophil functions, but the intracellular mechanisms underlying its modulation are unknown. Neutrophils are essential cells for host defense. Neutrophil effector functions include migration, reactive oxygen species (ROS) production, degranulation, and neutrophil extracellular trap (NET) formation. The goal of this study was to elucidate the signaling mechanism through which JAK2 modulates neutrophil function and the effect of aging on this pathway. We hypothesized that JAK2-mediated modulation changes the molecular mechanisms associated with neutrophil function in an age- and sex-dependent manner. Neutrophils from young (3 months) and aged (22+ months), male and female C57BL/6J mice were isolated, treated with a JAK2 inhibitor (AZD1480) or a pan-JAK inhibitor (Baricitinib), and stimulated with Phorbol 12-myristate 13-acetate (PMA). Functional assays were conducted to assess migration, ROS production, degranulation, NETosis, and metabolism. Mass spectrometry and Luminex assays provided proteomic and cytokine profiles. Our data show that JAK2 promotes migration via membrane composition and actin remodeling, with age-dependent shifts in chemokine secretion. JAK2 indirectly affects NETosis by modulating IL-1 signaling and ROS production. It also primes ROS production by altering NADPH oxidase components. In young neutrophils, JAK2 influences degranulation through actin remodeling, while aged neutrophils display impaired granule release. Metabolically, JAK2 enhances pentose phosphate pathway activity in young neutrophils and decreases glycogen breakdown in aged cells. These findings reveal mechanisms by which JAK2 modulates neutrophil function and suggest age-specific therapeutic targeting in inflammatory diseases.

immunology↗

Increasing Chlorophyll a Amid Stable Nutrient Concentrations in Rhode Island Lakes and Reservoirs

Addressing anthropogenic impacts on aquatic ecosystems is a focus of lake management. Controlling phosphorus and nitrogen can mitigate these impacts, but determining management effectiveness requires long-term datasets. Recent analysis of the LAke multi-scaled GeOSpatial and temporal database for the Northeast (LAGOSNE) United States found stable water quality in the northeastern and midwestern United States, however, sub-regional trends may be obscured. We analyze a sub-regional (i.e., 3000 km2) trend with the University of Rhode Islands Watershed Watch Volunteer Monitoring Program (URIWW) dataset. URIWW has collected water quality data on Rhode Island lakes and reservoirs for over 25 years. The LAGOSNE and URIWW datasets allow for comparison of water quality trends at regional and sub-regional extents, respectively. We assess regional (LAGOSNE) and state (URIWW) trends with yearly mean anomalies calculated on a per-station basis. Sub-regionally, temperature and chlorophyll a increased from 1993 to 2016. Total nitrogen shows a weak increase driven by low years in the early 1990s. Total phosphorus and the nitrogen:phosphorus ratio (N:P) were stable. At the regional scale, the LAGOSNE dataset shows similar trends to prior studies of the LAGOSNE with chlorophyll a, total nitrogen, total phosphorus, and N:P all stable over time. In short, algal biomass, as measured by chlorophyll a in Rhode Island lakes and reservoirs is increasing, despite stability in total nitrogen, total phosphorus, and the nitrogen to phosphorus ratio. This analysis suggests an association between lake temperature and primary production. Additionally, we demonstrate both the value of long-term monitoring programs, like URIWW, for identifying trends in environmental condition, and the utility of site-specific anomalies for analyzing for long-term water quality trends.

ecology↗