RESUMO
Given unprecedented rates of biodiversity loss, there is an urgency to better understand the ecological consequences of interactions among organisms that may lost or altered. Positive interactions among organisms of the same or different species that directly or indirectly improve performance of at least one participant can structure populations and communities and control ecosystem process. However, we are still in need of synthetic approaches to better understand how positive interactions scale spatio-temporally across a range of taxa and ecosystems. Here, we synthesize two complementary approaches to more rigorously describe positive interactions and their consequences among organisms, across taxa, and over spatio-temporal scales. In the first approach, which we call the mechanistic approach, we make a distinction between two principal mechanisms of facilitation-habitat modification and resource modification. Considering the differences in these two mechanisms is critical because it delineates the potential spatio-temporal bounds over which a positive interaction can occur. We offer guidance on improved sampling regimes for quantification of these mechanistic interactions and their consequences. Second, we present a trait-based approach in which traits of facilitators or traits of beneficiaries can modulate their magnitude of effect or how they respond to either of the positive interaction mechanisms, respectively. Therefore, both approaches can be integrated together by quantifying the degree to which a focal facilitator's or beneficiary's traits explain the magnitude of a positive effect in space and time. Furthermore, we demonstrate how field measurements and analytical techniques can be used to collect and analyze data to test the predictions presented herein. We conclude by discussing how these approaches can be applied to contemporary challenges in ecology, such as conservation and restoration and suggest avenues for future research.
RESUMO
Activation of microglia, the resident macrophages in the CNS, plays a significant role in neuronal death or degeneration in a broad spectrum of CNS disorders. Recent studies indicate that nanomolar concentrations of the serine protease, thrombin, can activate microglia in culture. However, in contrast to other neural cells responsive to thrombin, the participation of novel protease-activated receptors (PARs), such as the prototypic thrombin receptor PAR1, in thrombin-induced microglial activation was cast in doubt. In this report, by utilizing primary microglial cultures from PAR1 knockout (PAR1-/-) mice, application of the PAR1 active peptide TRAP-6 (SFLLRN) in comparison to a scrambled peptide (LFLNR), we have unambiguously demonstrated that murine microglia constitutively express PAR1 mRNA that is translated into fully functional protein. Activation of the microglial PAR1 induces a rapid cytosolic free [Ca2+]i increase and transient activation of both p38 and p44/42 mitogen-activated protein kinases. Moreover, although in part, this PAR1 activation directly contributes to thrombin-induced microglial proliferation. Furthermore, although not directly inducing tumor necrosis factor-alpha (TNF-alpha) release, PAR1 activation up-regulates microglial CD40 expression and potentiates CD40 ligand-induced TNF-alpha production, thus indirectly contributing to microglial activation. Taken together, these results demonstrate an essential role of PAR1 in thrombin-induced microglial activation. In addition, strategies aimed at blocking thrombin signaling through PAR1 may be therapeutically valuable for diseases associated with cerebral vascular damage and significant inflammation with microglial activation.