The Joshua tree (Yucca brevifolia, Y. jaegeriana) is a large, evergreen monocot distributed patchily across the southwestern United States. The plant occurs on alluvial fans, plains, and bajadas ...primarily in the Mojave Desert, but populations can also be found in the Great Basin and Sonoran Deserts. Named by the Mormon pioneers for the branching, supplicating arms reaching toward the sky, the species has become an emblematic symbol of the Mojave Desert for residents and visitors alike. Joshua trees inhabit cooler, moister microclimates within the larger desert macroclimate, and research has indicated the species may be vulnerable to future climatic regimes characterized by warmer and drier conditions. Here we present a concise review examining the past distribution, the current population status and threats, and the viability of the species under differing habitat and climate scenarios projected for the future. Additionally, we identify knowledge gaps to guide future research directions. Our results provide insight into management and conservation actions and contribute to a greater understanding of range-wide effects of ongoing environmental change on this species.
The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer ...patients who progressed on immunotherapy. Here we show that modelling of intermittent ceralasertib treatment in mouse tumor models reveals CD8
T-cell dependent antitumor activity, which is separate from the effects on tumor cells. Ceralasertib suppresses proliferating CD8
T-cells on treatment which is rapidly reversed off-treatment. Ceralasertib causes up-regulation of type I interferon (IFNI) pathway in cancer patients and in tumor-bearing mice. IFNI is experimentally found to be a major mediator of antitumor activity of ceralasertib in combination with PD-L1 antibody. Improvement of T-cell function after ceralasertib treatment is linked to changes in myeloid cells in the tumor microenvironment. IFNI also promotes anti-proliferative effects of ceralasertib on tumor cells. Here, we report that broad immunomodulatory changes following intermittent ATR inhibition underpins the clinical therapeutic benefit and indicates its wider impact on antitumor immunity.
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