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Pierce, A. J.

Publications and source records attributed to Pierce, A. J..

2 recordsLinked to original sources

Intraspecific trait variation shapes macro-scale patterns ofniche breadth and range size

Morphological variation within species may promote adaptation across ecological and geographic space, perhaps reflecting evolutionary plasticity and adaptability. Based on this concept, species with greater intraspecific variation in morphological traits may be expected to occupy broader ecological niches and larger geographic ranges. However, even in the age of global trait datasets, intraspecific morphological variation remains poorly quantified at broad taxonomic and geographic scales, limiting our understanding of how trait flexibility shapes ecological and biogeographic patterns. Focusing on 161 species of bulbuls, a widespread avian family containing some of the most abundant bird species in the world, along with some of the rarest and most restricted in range, we conducted global-scale sampling of morphological traits. These included beak shape, tarsus length and wing length, associated with dietary niche, foraging strategy and dispersal, respectively. Using phylogenetic models, we tested whether ecological niche breadth and geographical range size are predicted by intraspecific morphological variation quantified from 8,251 museum specimens and 5,627 live captures. Our results demonstrate that morphological trait variation predicts both ecological niche breadth and geographic range size. Furthermore, widespread species exhibit greater morphological variation than restricted-range species even when comparisons are constrained to equivalent geographic extents, consistent with the hypothesis that intraspecific trait variation facilitates range expansion rather than simply accumulating as a consequence of occupying a larger range. These results identify intraspecific morphological variation as a potentially important, yet largely overlooked, predictor of ecological traits and biogeographic distributions in birds.

ecology↗

OKN4395, a first-in-class EP2/EP4/DP1 triple antagonist reprograms prostanoid-driven immunosuppression to restore antitumor immunity

Immune checkpoint inhibitors, particularly T cell targeting anti-PD(L)1 therapies, have revolutionized the treatment landscape for solid malignancies, but challenges related to non-responsiveness and the development of treatment resistance continue to be observed. An additional immunosuppressive axis relates to prostaglandin signaling downstream of cyclooxygenase-2 (COX2), where COX2 inhibitors have shown clinical promise in re-engaging both T and non-T cell immune compartments, yet have suffered from toxicity concerns. We report here the preclinical characterization of OKN4395, a highly potent and specific first-in-class triple antagonist of EP2, EP4, and DP1, major tumor immunosuppressive receptors downstream of COX2. OKN4395 restores immune function on both T cells and NK cells in vitro. Additionally, OKN4395 acts synergistically with anti-PD1 to increase speed and depth of antitumor activity. Overall, these findings robustly support the clinical investigation of OKN4395 in an ongoing Phase 1 trial (NCT06789172) as an innovative cancer immunotherapy for solid tumors, as a single agent and in combination with anti-PD1 therapy. Statement of significanceOKN4395, a first-in-class oral EP2/EP4/DP1 antagonist, reverses prostanoid-driven immunosuppression to restore antitumor immunity. Integrated pharmacology defines mechanism, translational biomarkers as well as both monotherapy and anti-PD1 combination strategies. These data position prostanoid tri-receptor antagonism as a translatable strategy in solid tumors. A global Phase 1 study is underway (NCT06789172).

pharmacology and toxicology↗