Local and Systemic CD4 +

Investigation of the Th1 immune response in sarcoidosis CD4+ T cells has revealed reduced proliferative capacity and cytokine expression upon TCR stimulation. In other disease models, such cellular dysfunction has been associated with a step-wise, progressive loss of T cell function that results from chronic antigenic stimulation. T cell exhaustion is defined by decreased cytokine production upon TCR activation, decreased proliferation, increased expression of inhibitory cell surface receptors, and increased susceptibility to apoptosis. We characterized sarcoidosis CD4+ T cell immune function in systemic and local environments among subjects undergoing disease progression compared to those experiencing disease resolution. Spontaneous and TCR-stimulated Th1 cytokine expression and proliferation assays were performed in 53 sarcoidosis subjects and 30 healthy controls. PD-1 expression and apoptosis were assessed by flow cytometry. Compared to healthy controls, sarcoidosis CD4+ T cells demonstrated reductions in Th1 cytokine expression, proliferative capacity (p<0.05), enhanced apoptosis (p<0.01), and increased PD-1 expression (p<0.001). BAL-derived CD4+ T cells also demonstrated multiple facets of T cell exhaustion (p<0.05). Reversal of CD4+ T cell exhaustion was observed in subjects undergoing spontaneous resolution (p<0.05). Sarcoidosis CD4+ T cells exhibit loss of cellular function during progressive disease that follows the archetype of T cell exhaustion

RE-ARMing salt marshes: a resilience-experimentalist approach to prescribed fire and bird conservation in high marshes of the Gulf of Mexico

Uncertainty, complexity, and dynamic changes present challenges for conservation and natural resource management. Evidence-based approaches grounded in reliable information and rigorous analysis can enhance the navigation of the uncertainties and trade-offs inherent in conservation problems. This study highlights the importance of collaborative efforts and evidence-based decision-making, specifically implementing the Resilience-Experimentalist school of adaptive management (RE-ARM), which emphasizes stakeholder involvement, shared understanding, and experimentation. Our goal was to develop an adaptive management framework to reduce the uncertainty around the use of prescribed fire to manage the habitat for eastern black rails (Laterallus jamaicensis jamaicensis) and mottled ducks (Anas fulvigula) in saltmarshes of the Gulf of Mexico. Supported by discussions at a series of workshops, we used a value of information analysis to select a fire management hypothesis to test, developed an influence diagram to represent the system under fire management, used the influence diagram to develop a Bayesian decision network (BDN), and conducted a power analysis to guide management experiments and monitoring. Value of information analysis identified fire return interval as the critical uncertainty. Our BDN provided valuable insight into how managers believe prescribed fire influences vegetation characteristics and how vegetation influences both eastern black rail occupancy and mottled duck abundance. The results of the power analysis indicated that a standard occupancy modeling framework was more useful to compare 2- and 5-year fire return intervals for black rails than two alternative designs (removal and conditional). Our BDN can be used to predict the probability of achieving the desirable vegetative response to increase the occupancy probability of black rails and abundance of mottled ducks, and monitoring data can be used to update the BDN (learn) and improve best management practices for prescribed burns (adapt). Linking the value of information, BDNs, and power analysis enhances our understanding of the system, improves management decision-making, and builds trust among scientists, interested parties, and decision-makers. This approach lays the groundwork for knowledge co-production and adaptive management

Carvacrol, a Food-Additive, Provides Neuroprotection on Focal Cerebral Ischemia/Reperfusion Injury in Mice

Carvacrol (CAR), a naturally occurring monoterpenic phenol and food additive, has been shown to have antimicrobials, antitumor, and antidepressant-like activities. A previous study demonstrated that CAR has the ability to protect liver against ischemia/reperfusion injury in rats. In this study, we investigated the protective effects of CAR on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that CAR (50 mg/kg) significantly reduced infarct volume and improved neurological deficits after 75 min of ischemia and 24 h of reperfusion. This neuroprotection was in a dose-dependent manner. Post-treatment with CAR still provided protection on infarct volume when it was administered intraperitoneally at 2 h after reperfusion; however, intracerebroventricular post-treatment reduced infarct volume even when the mice were treated with CAR at 6 h after reperfusion. These findings indicated that CAR has an extended therapeutic window, but delivery strategies may affect the protective effects of CAR. Further, we found that CAR significantly decreased the level of cleaved caspase-3, a marker of apoptosis, suggesting the anti-apoptotic activity of CAR. Finally, our data indicated that CAR treatment increased the level of phosphorylated Akt and the neuroprotection of CAR was reversed by a PI3K inhibitor LY-294002, demonstrating the involvement of the PI3K/Akt pathway in the anti-apoptotic mechanisms of CAR. Due to its safety and wide use in the food industry, CAR is a promising agent to be translated into clinical trials