Island species are difficult to conserve because they face the synergy of climate change, invasive species, deforestation, and increasing human population densities in areas where land mass is shrinking. The Caribbean island of Hispaniola presents particular challenges because of geopolitical complexities that span 2 countries and hinder coordinated management of species across the island. We employed species distribution modeling to evaluate the impacts of climatic change and anthropogenic activities on the distribution of an endemic mammal of conservation concern, the Hispaniolan solenodon (Solenodon paradoxus). We aggregated occurrence points for this poorly known species for the Last Glacial Maximum (LGM) and the present (1975–2016) based on museum collections, online biodiversity databases, and new field surveys. We quantified degree of overlap between periods and scenarios with Schoener's D. Through a conservation paleobiology lens, we found that over time humans played an increasing role in shaping the distribution of S. paradoxus, thus, providing a foundation for developing conservation strategies on appropriate spatiotemporal scales. Human population density was the single most important predictor of S. paradoxus occurrence. Densities >166 people/km2 corresponded to a near‐zero probability of occurrence. Models that accounted for climate but not anthropogenic variables falsely identified suitable habitat in Haiti, where on‐the‐ground surveys confirm habitat is unavailable. Climate‐only models also significantly overestimated the potential for habitat connectivity between isolated populations. Our work highlights that alternative fates for S. paradoxus in the Anthropocene exist across the political border between the Dominican Republic and Haiti due to the fundamentally different economic and political realities of each country. Relationships in the fossil record confirm that Hispaniola's sociopolitical boundary is not biologically significant but instead represents one imposed on the island's fauna in the past 500 years by colonial activity. Our approach reveals how a paleontological perspective can contribute to concrete management insights.
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, Schwann cell-derived neoplasms of the peripheral nervous system that have recently been shown to possess an autocrine CXCL12/CXCR4 signaling loop that promotes tumor cell proliferation and survival. Importantly, the CXCL12/CXCR4 signaling axis is driven by availability of the CXCL12 ligand rather than CXCR4 receptor levels alone. Therefore, pharmacological reduction of CXCL12 expression could be a potential chemotherapeutic target for patients with MPNSTs or other pathologies wherein the CXCL12/CXCR4 signaling axis is active. AT101 is a well-established BCL-2 homology domain 3 (BH3) mimetic that we recently demonstrated functions as an iron chelator and thus acts as a hypoxia mimetic. In this study, we found that AT101 significantly reduces CXCL12 mRNA and secreted protein in established human MPNST cell lines in vitro. This effect was recapitulated by other BH3 mimetics [ABT-737 (ABT), obatoclax (OBX) and sabutoclax (SBX)] but not by desferrioxamine (DFO), an iron chelator and known hypoxia mimetic. These data suggest that CXCL12 reduction is a function of AT101's BH3 mimetic property rather than its iron chelation ability. Additionally, this study investigates a potential mechanism of BH3 mimetic-mediated CXCL12 suppression: liberation of a negative CXCL12 transcriptional regulator, poly (ADP-Ribose) polymerase I (PARP1) from its physical interaction with BCL-2. These data suggest that clinically available BH3 mimetics might prove therapeutically useful at least in part by virtue of their ability to suppress CXCL12 expression.
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