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Richardson, B. A.

Publications and source records attributed to Richardson, B. A..

2 recordsLinked to original sources

Environment predicts the maintenance of reproductive isolation in a mosaic hybrid zone of rubber rabbitbrush

Widely distributed plants of western North America experience divergent selection across environmental gradients, have complex histories shaped by biogeographic barriers and distributional shifts, and often illustrate continuums of reproductive isolation. Rubber rabbitbrush (Ericameria nauseosa) is a foundational shrub species that occurs across diverse environments of western North America. Its remarkable phenotypic diversity is currently ascribed to two subspecies - E. n. nauseosa and E. n. consimilis - and 22 named varieties. We analyzed how genetic variation is partitioned across subspecies, varieties, and environment using high throughput sequencing of reduced representation libraries. We found clear evidence for divergence between the two subspecies, despite largely sympatric distributions. Numerous locations exhibiting admixed ancestry were not geographically localized but were widely distributed across a mosaic hybrid zone. The occurrence of hybrid and subspecific ancestries was strongly predicted by environmental variables as well as the proximity to major ecotones between ecoregions. Although this repeatability illustrates the importance of environmental factors in shaping reproductive isolation, variability in the outcomes of hybridization also indicated these factors likely differ across ecological contexts. There was mixed evidence for the evolutionary cohesiveness of varieties, but several genetically distinct and narrow endemic varieties exhibited admixed subspecific ancestries, hinting at the possibility for transgressive hybridization to contribute to phenotypic novelty and the colonization of new environments in E. nauseosa.

evolutionary biology↗

Enhancing natural killer cell function with gp41-targeting bispecific antibodies to combat HIV infection

Objective(s)To develop and evaluate the activity of bispecific antibodies (bsAbs) to enhance NK cell antibody-dependent cellular cytotoxicity (ADCC) against HIV-infected cells.\n\nDesignThese bsAbs are based on patient-derived antibodies targeting the conserved gp41 stump of HIV Env, and also incorporate a high affinity scFv targeting the activating receptor CD16 on NK cells. Overall, we expect the bsAbs to provide increased affinity and avidity over their corresponding monoclonal antibodies, allowing for improved ADCC activity against Env-expressing target cells.\n\nMethodsbsAbs and their corresponding mAbs were expressed in 293T cells and purified. The binding of bsAbs and mAbs to their intended targets was determined using Bio-Layer Interferometry, as well as flow cytometry-based binding assays on in vitro infected cells. The ability of these bsAbs to improve NK cell activity against HIV-infected cells was tested using in vitro co-culture assays, using flow cytometry and calcein release to analyze NK cell degranulation and target cell killing, respectively.\n\nResultsThe bsAbs bound gp41 with similar affinity to their corresponding mAbs, and had increased affinity for CD16. The bsAbs also bound to primary CD4 T cells infected in vitro with two different strains of HIV. In addition, the bsAbs induce increased NK cell degranulation and killing of autologous HIV-infected CD4 T cells.\n\nConclusionsThese bsAbs may provide a promising strategy to improve NK-mediated immune targeting of infected cells during HIV infection.

immunology↗