No abstract

How underlying mechanisms bias evolution toward predictable outcomes remains an area of active debate. In this study, we leveraged phenotypic plasticity and parallel adaptation across independent lineages of Trinidadian guppies (Poecilia reticulata) to assess the predictability of gene expression evolution during parallel adaptation. Trinidadian guppies have repeatedly and independently adapted to high‐ and low‐predation environments in the wild. We combined this natural experiment with a laboratory breeding design to attribute transcriptional variation to the genetic influences of population of origin and developmental plasticity in response to rearing with or without predators. We observed substantial gene expression plasticity, as well as the evolution of expression plasticity itself, across populations. Genes exhibiting expression plasticity within populations were more likely to also differ in expression between populations, with the direction of population differences more likely to be opposite those of plasticity. While we found more overlap than expected by chance in genes differentially expressed between high‐ and low‐predation populations from distinct evolutionary lineages, the majority of differentially expressed genes were not shared between lineages. Our data suggest alternative transcriptional configurations associated with shared phenotypes, highlighting a role for transcriptional flexibility in the parallel phenotypic evolution of a species known for rapid adaptation.

No abstract

Oral mucositis (OM) is a common complication in cancer patients undergoing anticancer treatment. Despite the clinical and economic consequences of OM, there are no drugs available for its fundamental control. Here we show that high-mobility group box 1 (HMGB1), a "danger signal" that acts as a potent innate immune mediator, plays a critical role in the pathogenesis of OM. In addition, we investigated treatment of OM through HMGB1 blockade using NecroX-7 (tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxothiomorpholin-4-yl)methyl-1Hindole-7-yl]amine). NecroX-7 ameliorated basal layer epithelial cell death and ulcer size in OM induced by chemotherapy or radiotherapy. This protective effect of NecroX-7 was mediated by inhibition of HMGB1 release and downregulation of mitochondrial oxidative stress. Additionally, NecroX-7 inhibited the HMGB1-induced release of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and macrophage inflammatory protein (MIP)-1β, as well as the expression of p53upregulated modulator of apoptosis (PUMA) and the excessive inflammatory microenvironment, including nuclear factor-kB (NF-kB) pathways. In conclusion, our findings suggest that HMGB1 plays a key role in the pathogenesis of OM; therefore, blockade of HMGB1 by NecroX-7 may be a novel therapeutic strategy for OM.

No abstract