Nuclear receptor-mediated gene expression is proposed to be regulated by the ordered recruitment of large protein complexes in which activity depends on mutual interactions and posttranslational modifications. In contrast, relatively little attention has been given to mechanisms regulating the expression of the coregulator proteins themselves. Previously we have shown that the ligand-dependent corepressor, RIP140, is a direct transcriptional target of all-trans retinoic acid (RA). Here we demonstrate that RA induction of RIP140 constitutes a rate-limiting step in the regulation of retinoic acid receptor signaling. Silencing of the RA induction of RIP140 dramatically enhances and accelerates retinoid receptor transactivation, endogenous expression of other RA target genes, and RA-induced neuronal differentiation and cell cycle arrest in human embryonal carcinoma cells. The data suggest that RA induction of RIP140 constitutes a functional negative feedback loop that limits activation of retinoid receptors in the continued presence of RA and that acutely regulated expression of coregulators may be a general regulatory mechanism in hormonal signaling.

As conservation shifts to meet the challenges of our globalized world, approaches for planning and evaluating interventions must evolve to account for the increasing complexity of conservation problems and the dynamic, multiscalar relationships between humans and the environment. Systems thinking offers approaches that could help conservation be more adaptive, transparent, and evidence-based. Using case studies and the literature, we trace the evolution of systems thinking and demonstrate how systems mapping could support the process of planning and evaluating interventions. Systems mapping helps disentangle the context of conservation and encourage collaborative planning that integrates diverse views. It can also change the way interventions are characterized and communicated by emphasizing the systems targeted for change as opposed to actions. Last, it can encourage evidence-based decision-making by identifying indicators attune to complexity, prompting discussion on knowledge gaps, and filling gaps through qualitative mapping or computational modeling. Integrating systems thinking in practice will help practitioners foster the capacity for learning and adaptation required for conservation to deliver global results.

Conservation practitioners routinely work within complex social-ecological systems to address threats facing biodiversity and to promote positive human-wildlife interactions. Inadequate understanding of the direct and indirect, short- and long-term consequences of decision making within these dynamic systems can lead to misdiagnosed problems and interventions with perverse outcomes, exacerbating conflict. Participatory system dynamics (SD) modeling is a process that encourages stakeholder engagement, synthesizes research and knowledge, increases trust and consensus and improves transdisciplinary collaboration to solve these complex types of problems. Tiger conservation exemplifies a set of interventions in a complex social-ecological system. Wild tigers remain severely threatened by various factors, including habitat constraints, human-wildlife conflict, and persistent consumer demand for their body parts. Opinions differ on whether commercial captive tiger facilities reduce or increase the threat from poaching for trade, resulting in policy conflict among diverse stakeholder groups. This paper explains how we are working with international conservation partners in a virtual environment to utilize a participatory SD modeling approach with the goal of better understanding and promoting coexistence of humans and wild tigers. We highlight a step-by-step process that others might use to apply participatory SD modeling to address similar conservation challenges, building trust and consensus among diverse partners to reduce conflict and improve the efficacy of conservation interventions.

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