RESUMO
Meeting international commitments to protect 17% of terrestrial ecosystems worldwide will require >3 million square kilometers of new protected areas and strategies to create those areas in a way that respects local communities and land use. In 2000-2016, biological and social scientists worked to increase the protected proportion of Peru's largest department via 14 interdisciplinary inventories covering >9 million hectares of this megadiverse corner of the Amazon basin. In each landscape, the strategy was the same: convene diverse partners, identify biological and sociocultural assets, document residents' use of natural resources, and tailor the findings to the needs of decision-makers. Nine of the 14 landscapes have since been protected (5.7 million hectares of new protected areas), contributing to a quadrupling of conservation coverage in Loreto (from 6 to 23%). We outline the methods and enabling conditions most crucial for successfully applying similar campaigns elsewhere on Earth.
RESUMO
BACKGROUND: Sepsis, a life-threatening organ dysfunction caused by a dysregulated systemic immune response to infection, associates with reduced responsiveness to subsequent infections. How such tolerance is acquired is not well understood but is known to involve epigenetic and transcriptional dysregulation. METHODS: Bead arrays were used to compare global DNA methylation changes in patients with sepsis, non-infectious systemic inflammatory response syndrome, and healthy controls. Bioinformatic analyses were performed to dissect functional reprogramming and signaling pathways related to the acquisition of these specific DNA methylation alterations. Finally, in vitro experiments using human monocytes were performed to test the induction of similar DNA methylation reprogramming. RESULTS: Here, we focused on DNA methylation changes associated with sepsis, given their potential role in stabilizing altered phenotypes. Tolerized monocytes from patients with sepsis display changes in their DNA methylomes with respect to those from healthy controls, affecting critical monocyte-related genes. DNA methylation profiles correlate with IL-10 and IL-6 levels, significantly increased in monocytes in sepsis, as well as with the Sequential Organ Failure Assessment score; the observed changes associate with TFs and pathways downstream to toll-like receptors and inflammatory cytokines. In fact, in vitro stimulation of toll-like receptors in monocytes results in similar gains and losses of methylation together with the acquisition of tolerance. CONCLUSION: We have identified a DNA methylation signature associated with sepsis that is downstream to the response of monocytes to inflammatory signals associated with the acquisition of a tolerized phenotype and organic dysfunction.