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Schwarz, P. F.

Publications and source records attributed to Schwarz, P. F..

2 recordsLinked to original sources

Introgression and Parental Conflict Underlie Repeated Occurrences of Postzygotic Isolation

Postzygotic reproductive isolation is often thought to accumulate as a byproduct of neutral divergence. Yet, it frequently evolves rapidly, in line with non-neutral evolution. A major driver of intrinsic postzygotic reproductive barriers are intragenomic conflicts, such as conflict between maternal and paternal interests in resource allocation to offspring (i.e. parental conflict). Parental conflict may underlie hybrid seed inviability, a common and rapidly evolving reproductive barrier in angiosperms. Yet, in closely related, hybridizing species, it remains unclear how intragenomic conflicts and introgression interact to determine the fate of incompatibility alleles in nature. Here, we explore repeated incidences of hybrid seed inviability in a rising model: the Mimulus guttatus species complex. Using an extensive, range-wide crossing survey, we discover patterns of hybrid seed inviability within the widespread M. guttatus that are better described by geography than phylogeny. These patterns of reproductive isolation transgress species boundaries, as geographically-proximate but phylogenetically-distant species also exhibit similar patterns of hybrid seed inviability with allopatric populations of M. guttatus. We find strong support that patterns of reproductive isolation are consistent with parental conflict. Lastly, we provide evidence that introgression may underlie shared patterns of hybrid seed inviability between two species within this complex. Such introgression could have led to cascading reproductive isolation with other closely related species, creating a complex landscape of incompatibility. Overall, this work suggests that parental conflict and introgression can interact to shape the rapid and repeated evolution of strong reproductive isolation in the wild.

evolutionary biology↗

Primulagenin A is a potent inverse agonist of the nuclear receptor RAR-related orphan receptor gamma (RORγ)

Throughout history, herbal medicines and natural products have played a crucial role as therapeutics for humans, yet their molecular mechanisms of action often remain elusive. Here, we ask whether primulagenin A (PGA) from the traditionally used herbal substance Primula root, acts via the nuclear receptor ROR{gamma}, a key regulator of pro-inflammatory Th17 cells, which are linked to autoimmune diseases like psoriasis. Luciferase assays revealed a high potency (IC50 ~100 nM) and efficacy (Imax ~ 90%) of PGA as an inverse agonist of ROR{gamma}. To ensure sufficient supply, we established methods to isolate and synthesize PGA. Its binding to the human ROR{gamma} ligand binding domain was confirmed by nano differential scanning fluorimetry, and a structure-activity relationship was proposed by docking and site-directed mutagenesis. PGA downregulated ROR{gamma} target gene expression and inhibited murine and human Th17 differentiation in a concentration-dependent manner. It also reduced the proportion of IL-17A-producing Th17 cells. In this work, we identify PGA as a new, potent, and efficacious inverse agonist of ROR{gamma}, with potential for modulating immune responses in inflammatory and autoimmune diseases.

pharmacology and toxicology↗