bioRxiv Science⌕ Search

Biology subjects

Stedman, J.

Publications and source records attributed to Stedman, J..

2 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↗

Small molecule allosteric inhibitors of RORγt block Th17-dependent inflammation and associated gene expression in vivo.

Retinoic acid receptor-related orphan nuclear receptor (ROR) {gamma}t is a member of the RORC nuclear hormone receptor family of transcription factors. ROR{gamma}t functions as a critical regulator of thymopoiesis and immune responses. ROR{gamma}t is expressed in multiple immune cell populations including Th17 cells, where its primary function is regulation of immune responses to bacteria and fungi through IL-17A production. However, excessive IL-17A production has been linked to numerous autoimmune diseases. Moreover, Th17 cells have been shown to elicit both pro- and anti-tumor effects. Thus, modulation of the ROR{gamma}t/IL-17A axis may represent an attractive therapeutic target for the treatment of autoimmune disorders and some cancers. Herein we report the design, synthesis and characterization of three selective allosteric ROR{gamma}t inhibitors in preclinical models of inflammation and tumor growth. We demonstrate that these compounds can inhibit Th17 differentiation and maintenance in vitro and Th17-dependent inflammation and associated gene expression in vivo, in a dose-dependent manner. Finally, ROR{gamma}t inhibitors were shown to inhibit tumor formation in pancreatic ductal adenocarcinoma (PDAC) organoids.

immunology↗