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Jones, M. F.

Publications and source records attributed to Jones, M. F..

2 recordsLinked to original sources

A holistic survey of small mammal diversity across an iconic Madrean Sky Island (Santa Catalina Mountains, Arizona, USA)

The Santa Catalina Mountains are an iconic member of the Madrean Sky Islands, rising above Tucson, Arizona, USA, where the Catalina Highway connects Sonoran desertscrub to stands of conifer forest nearly 2,800 meters in elevation. As one of the [~]54 forested mountain areas in this system, the Santa Catalinas host unique biotic communities relative to the surrounding lowlands. However, most of these sky islands lack the surveys of resident small mammals (either historical or recent) needed for studying biodiversity in the context of changing climate and habitat use. From 2021 to 2023, we surveyed 10 localities on the north and south slopes of the Santa Catalina Mountains using holistic sampling methods to document terrestrial small mammal diversity and preserve multiple tissue types. Here we summarize these new collections relative to previous voucher specimens and human observations, identifying gaps for future work to address. Our survey recorded the presence of 15 species, preserved 150 voucher specimens paired with a suite of flash-frozen tissues, and non-lethally sampled another 219 individuals (ear tissue, feces, ectoparasites, and measurements) to provide populational data from sites where vouchering occurred. Despite the road accessibility and long history of sampling in the Santa Catalina Mountains, our surveys extended the known elevational range for 8 species, including the first known specimen of Reithrodontomys fulvescens from the area. Our use of a transect-based survey design, which maximizes species diversity across biotic communities, paired with holistic specimen preservation techniques, provides a model for surveying patterns of population genetic and parasite sharing relationships across other Madrean Sky Islands, bridging a [~]40 year lull in specimen preservation while adding new data dimensions that promote integrative studies of small mammal biodiversity. With more complete sampling, other mountains will offer promising replicates for studying eco-evolutionary impacts of the regions episodic habitat connectivity. Teaser textSurveying the terrestrial small mammals of the Santa Catalina Mountains, part of the Madrean Sky Islands, we analyze modern occurrences relative to previous records and demonstrate the potential value of holistically surveying sky island small mammals.

zoology↗

Multi-selective RAS(ON) Inhibition Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 and BCL2 Inhibitors in Acute Myeloid Leukemia

Aberrant activation of the RAS/MAPK signaling limits the clinical efficacy of several targeted therapies in acute myeloid leukemia (AML). In FLT3-mutant AML, the selection of clones harboring heterogeneous RAS mutations drives resistance to FLT3 inhibitors (FLT3i). RAS activation is also associated with resistance to other AML targeted therapies, including the BCL2 inhibitor venetoclax. Despite the critical need to inhibit RAS/MAPK signaling in AML, no targeted therapies have demonstrated clinical benefit in RAS-driven AML. To address this unmet need, we investigated the preclinical activity of RMC-7977, a multi-selective inhibitor of GTP-bound active [RAS(ON)] isoforms of mutant and wild-type RAS in AML models. RMC-7977 exhibited potent antiproliferative and pro-apoptotic activity across AML cell lines with MAPK-activating signaling mutations. In cell line models with acquired FLT3i resistance due to secondary RAS mutations, treatment with RMC-7977 restored sensitivity to FLT3i. Similarly, RMC-7977 effectively reversed resistance to venetoclax in RAS-addicted cell line models with both RAS wild-type and mutant genetic backgrounds. In murine patient-derived xenograft models of RAS-mutant AML, RMC-7977 was well tolerated and significantly suppressed leukemic burden in combination with gilteritinib or venetoclax. Our findings strongly support clinical investigation of broad-spectrum RAS(ON) inhibition in AML to treat and potentially prevent drug resistance due to activated RAS signaling.

cancer biology↗