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McNamara, K.

Publications and source records attributed to McNamara, K..

3 recordsLinked to original sources

Decision analysis in support of proactive planning for chronic wasting disease in Vermont, USA

Chronic wasting disease (CWD), a fatal, transmissible disease in white-tailed deer (Odocoileus virginianus) and related species, is spreading across North America but has not yet been detected in Vermont, United States (U.S.). The Vermont Department of Fish and Wildlife, along with partner agencies, wants to develop a proactive prevention and response plan in anticipation of the eventual detection of the disease. Between September 2023 and September 2025, staff from the U.S. Geological Survey and the University of Vermont facilitated a structured decision-making (SDM) process with seven State and Federal agencies that have jurisdiction over some aspect of CWD management in Vermont. The aim of this process was to generate and evaluate alternative response plans against a range of long-term objectives important to the agencies. To aid in the evaluation of the alternatives, we developed a linked set of models for white-tailed deer population and disease dynamics, hunter participation and health, forest health, economic consequences, and agricultural opportunities related to the actions being contemplated as part of the response plan. We evaluated over 256 different permutations of management actions and used multi-criteria decision analysis, a branch of decision analysis designed to help decision makers navigate tradeoffs among competing objectives, to summarize the performance of those alternative strategies against the desired outcomes. Proactive actions, those designed to slow the arrival of CWD to Vermont, were moderately effective, but the most important proactive action was surveillance to detect the disease early after arrival, which triggered response actions after detection. With the insights generated by the SDM process and the results of the analyses, the participating agencies were able to identify a preferred strategy and outline the elements of a proactive response plan. This report describes the SDM process, the technical details of the modeling work, and the results of the analyses.

ecology↗

Conserved Molecular Function and Regulatory Subfunctionalization of the LORELEI Gene Family in Brassicaceae

A signaling complex comprising members of the LORELEI (LRE)-LIKE GPI-anchored protein (LLG) and Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE (CrRLK1L) families perceive RAPID ALKALINIZATION FACTOR (RALF) peptides and regulate growth, reproduction, immunity, and stress responses in Arabidopsis. Genes encoding these proteins are members of multi-gene families in most angiosperms and could generate thousands of signaling complex variants. However, the link(s) between expansion of these gene families and the functional diversification of this critical signaling complex as well as the evolutionary factors underlying the maintenance of gene duplicates remain unknown. Here, we investigated LLG gene family evolution, function, and expression in angiosperms. We found that LLGs in monocots and eudicots are descendants of a duplication early in angiosperm evolution and that both ancient and recent LLG duplicates are retained. Complementation and expression analysis showed that expression divergence of LLGs (regulatory subfunctionalization), rather than functional divergence, explains the retention of paralogs in Brassicales. All but one extant monocot and eudicot species examined maintained an LLG copy with preferential expression in male reproductive tissues, with the other duplicate copies showed highest levels of expression in female or vegetative tissues. Interestingly, the single LLG copy in Amborella (sister to all other angiosperms) is expressed vastly higher in male compared to female reproductive or vegetative tissues. Reconstruction of expression evolution showed that the highest inferred expression levels for the single copy ancestral angiosperm LLG was in male reproductive tissues. We propose that expression divergence played an important role in maintenance of LLG duplicates in angiosperms. One Sentence SummaryExpression divergence played an important role in maintenance of two sub-groups of LLG duplicates in angiosperms

plant biology↗

Clonal replacement of tumor-specific T cells following PD-1 blockade

Immunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of cancer patients. However, which tumor-specific T cells are mobilized following checkpoint blockade remains unclear. Here, we performed paired single-cell RNA- and T cell receptor (TCR)-sequencing on 79,046 cells from site-matched tumors from patients with basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) pre- and post-anti-PD-1 therapy. Tracking TCR clones and transcriptional phenotypes revealed a coupling of tumor-recognition, clonal expansion, and T cell dysfunction: the T cell response to treatment was accompanied by clonal expansions of CD8+CD39+ T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, this expansion did not derive from pre-existing tumor infiltrating T cell clones; rather, it comprised novel clonotypes, which were not previously observed in the same tumor. Clonal replacement of T cells was preferentially observed in exhausted CD8+ T cells, compared to other distinct T cell phenotypes, and was evident in BCC and SCC patients. These results, enabled by single-cell multi-omic profiling of clinical samples, demonstrate that pre-existing tumor-specific T cells may be limited in their capacity for re-invigoration, and that the T cell response to checkpoint blockade relies on the expansion of a distinct repertoire of T cell clones that may have just recently entered the tumor.

immunology↗