Demography and space-use of Eastern Red-backed Salamanders (Plethodon cinereus) between mature and successional forests.

Space-use and demographic processes are critical to the persistence of populations across space and time. Despite their importance, estimates of these processes are often derived from a limited number of populations spanning broad habitat or environmental gradients. With increasing appreciation of the role fine-scale environmental variation in microgeographic adaptation, there is a need and value to assessing within-site variation in space-use and demographic patterns. In this study, we analyze 3 years of spatial capture-recapture data on the Eastern Red-backed Salamander collected from a mixed-use deciduous forest site in central Ohio, USA. Study plots were situated in both a mature forest stand and successional forest stand separated by <100-m distance. Our results showed that salamander density was reduced on successional plots, which corresponded with greater distance between nearest neighbors, less overlap in core use areas, greater space-use, and greater shifts in activity centers when compared to salamanders occupying the mature habitat. By contrast, individual growth rates of salamanders occupying the successional forest were significantly greater than salamanders in the mature forest. These estimates result in successional plot salamanders reaching maturity more than 1 year earlier than salamanders on the mature forest plots and increasing their estimated lifetime fecundity by as much as 43%. The patterns we observed in space-use and individual growth are likely the result of density-dependent processes, potentially reflecting differences in resource availability or quality. Our study highlights how fine-scale, within-site variation can shape population demographics. As research into the demographic and population consequences of climate change and habitat loss and alteration continue, future research should take care to acknowledge the role that fine-scale variation may play, especially for abiotically sensitive organisms with limited vagility.

Cardiac myosin-Th17 responses promote heart failure in human myocarditis.

In human myocarditis and its sequela dilated cardiomyopathy (DCM), the mechanisms and immune phenotype governing disease and subsequent heart failure are not known. Here, we identified a Th17 cell immunophenotype of human myocarditis/DCM with elevated CD4+IL17+ T cells and Th17-promoting cytokines IL-6, TGF-ß, and IL-23 as well as GM-CSF-secreting CD4+ T cells. The Th17 phenotype was linked with the effects of cardiac myosin on CD14+ monocytes, TLR2, and heart failure. Persistent heart failure was associated with high percentages of IL-17-producing T cells and IL-17-promoting cytokines, and the myocarditis/DCM phenotype included significantly low percentages of FOXP3+ Tregs, which may contribute to disease severity. We demonstrate a potentially novel mechanism in human myocarditis/DCM in which TLR2 peptide ligands from human cardiac myosin stimulated exaggerated Th17-related cytokines including TGF-ß, IL-6, and IL-23 from myocarditic CD14+ monocytes in vitro, and an anti-TLR2 antibody abrogated the cytokine response. Our translational study explains how an immune phenotype may be initiated by cardiac myosin TLR ligand stimulation of monocytes to generate Th17-promoting cytokines and development of pathogenic Th17 cells in human myocarditis and heart failure, and provides a rationale for targeting IL-17A as a therapeutic option.

Autoimmune myocarditis, valvulitis, and cardiomyopathy.

Myocarditis and valvulitis are inflammatory diseases affecting myocardium and valve. Myocarditis, a viral-induced disease of myocardium, may lead to dilated cardiomyopathy and loss of heart function. Valvulitis leads to deformed heart valves and altered blood flow in rheumatic heart disease. Animal models recapitulating these diseases are important in understanding the human condition. Cardiac myosin is a major autoantigen in heart, and antibodies and T cells to cardiac myosin are evident in inflammatory heart diseases. This unit is a practical guide to induction and evaluation of experimental autoimmune myocarditis (EAM) in several mouse strains and the Lewis rat. Purification protocols for cardiac myosin and protocols for induction of EAM by cardiac myosin and its myocarditis-producing peptides, and coxsackievirus CVB3, are defined. Protocols for assessment of myocarditis and valvulitis in humans and animal models provide methods to define functional autoantibodies targeting cardiac myosin, ß-adrenergic, and muscarinic receptors, and their deposition in tissues.