bioRxiv Science⌕ Search

Biology subjects

Stanley, A.

Publications and source records attributed to Stanley, A..

5 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↗

Shifts in consumer assemblages are linked to nutrient availability and ecosystem metabolism

Nutrient availability, ecosystem productivity, and consumer assemblages are intricately linked through complex interactions and feedbacks. Nutrients influence the diversity and functional roles of consumers via shifts in resource quality and quantity, and consumers can alter ecosystem production and nutrient availability. However, our understanding of how characteristics of consumers respond to and influence concomitant shifts in nutrient availability and production is limited. We quantified the response of well-studied consumer assemblages (benthic invertebrates and zooplankton) to realistic nutrient loads that altered gross primary production (GPP) and ecosystem respiration (ER). We fertilized 14 outdoor experimental ponds for 2 months and monitored total water column carbon (TC), nitrogen (TN), and phosphorus (TP), GPP, ER, and net ecosystem production (NEP) weekly. Then, we evaluated how fertilization and the variation in nutrients and metabolism caused by fertilization were related to shifts in consumer assemblages. Fertilization increased water column TN and TP and reduced TC:TP ratios, TN:TP ratios, and rates of GPP and ER. However, consumer assemblages were more tightly linked to variation in nutrient availability and production across ponds than to fertilization. Greater declines in benthic diversity occurred in ponds with higher average TN:TP ratios during the experiment. Consistent with predicted effects of cladocerans on nutrient availability, shifts in cladoceran abundances were positively associated with average water column TN:TP ratios during the experiment. Finally, elevated GPP and ER were associated with greater increases in the abundance of benthic invertebrate predators, suggesting the possibility of top-down control. Our study highlights the critical role of consumer-mediated processes in the interaction between nutrient availability and production. Manuscript HighlightsO_LIFertilization reduced pond gross primary production and ecosystem respiration rates. C_LIO_LIInvertebrate predator abundance was inversely related to gross primary production. C_LIO_LIShifts in consumer assemblages were tightly linked to nutrients and production. C_LI

ecology↗

Measuring the Stoichiometry of Microbial Parasite Infrapopulations One Cell at a Time using Energy Dispersive Spectroscopy

O_LIProgress in the field of ecological stoichiometry has demonstrated that the outcome of ecological interactions can often be predicted a priori based on the nutrient ratios (e.g., carbon: nitrogen: phosphorus, C:N:P) of interacting organisms. However, the challenges of accurately measuring the nutrient content of active parasites within hosts has limited our ability to rigorously apply ecological stoichiometry to host-parasite systems. Traditional nutrient analyses require high parasite biomasses, often preventing individual-level analyses. This prevents researchers from estimating variation in the nutrient content of individual parasites within a single host infrapopulation, a critical factor that could define how the ecology of the parasite affects the host-parasite interaction. C_LIO_LIHere, we explain how energy dispersive technology, a technique currently used to measure the elemental content of free-living microbes, can be adapted for parasitic microbial infrapopulations. We demonstrate the power of accurately quantifying the biomass stoichiometry of individual microbial parasites sampled directly from individual hosts. C_LIO_LIUsing this approach we show that the stoichiometric composition of two microbial parasites capable of infecting the same host are stoichiometrically distinct and respond to host diet quality differently. We also demonstrate that characteristics of the stoichiometric trait distributions of these infrapopulations were important predictors of host fecundity, a proxy for virulence in this system, and better predictors of parasite load than the mean parasite stoichiometry or our parasite and diet treatments alone. C_LIO_LIEDS provides a rigorous tool for applying ecological stoichiometry to host-parasite systems and enables researchers to explore the nutritional physiology of host-parasite interactions at a scale that is more relevant to the ecology and evolution of the system than traditional nutrient analyses. Here we demonstrate that this level of resolution provides useful insights into the diet-dependent physiology of microbial parasites and their hosts. We anticipate that this improved level of resolution has the potential to elucidate a range of eco-evo interactions in host-parasite systems that were previously unobservable. C_LI

ecology↗

Conserved and cell type-specific transcriptional responses to IFN-γ in the ventral midbrain

Dysregulated inflammation within the central nervous system (CNS) contributes to neuropathology in infectious, autoimmune, and neurodegenerative disease. With the exception of microglia, major histocompatibility complex (MHC) proteins are virtually undetectable in the mature, healthy central nervous system (CNS). Neurons have generally been considered incapable of antigen presentation, and although interferon gamma (IFN-{gamma}) can elicit neuronal MHC class I (MHC-I) expression and antigen presentation in vitro, it remains unclear whether similar responses occur in vivo. Here we directly injected IFN-{gamma} into the ventral midbrain of mature mice and analyzed gene expression profiles of specific CNS cell types. We find that IFN-{gamma} induces cellular proliferation and expression of MHC-II and associated genes only in microglia. However, IFN-{gamma} upregulated MHC-I and associated mRNAs in ventral midbrain microglia, astrocytes, oligodendrocytes, and GABAergic, glutamatergic, and dopaminergic neurons. The core set of IFN-{gamma}-induced genes and their response kinetics were conserved across neurons and glia, with a lower amplitude of expression in neurons. A diverse repertoire of genes was upregulated in glia, particularly microglia, while no neuron-specific responses to IFN-{gamma} were observed. Using mutant mice to selectively delete the IFN-{gamma}-binding domain of IFNGR1 in dopaminergic neurons, we demonstrate that dopaminergic neurons respond directly to IFN-{gamma}. Our results suggest that most neurons are capable of responding directly to IFN-{gamma} and upregulating MHC-I and related genes in vivo, but their expression amplitude and repertoire is limited compared to oligodendrocytes, astrocytes, and microglia. One-sentence summaryWe find that IFN-{gamma} induces transcription of MHC class I antigen processing and presentation machinery in all major parenchymal cell types in the ventral midbrain; however, neuronal responses are low amplitude and limited to a small set of genes, MHC class II expression and cellular proliferation are restricted to microglia, and dopamine neuronal responses require cell autonomous expression of IFNGR1.

neuroscience↗

Design of a novel DNA Gyrase B inhibitor with a rhodanine scaffold: in silico and in vitro approaches

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin intermediate-resistant Staphylococcus aureus (VRSA) is one among the WHO high priority pathogens. Among these two, MRSA is the most globally documented pathogen that necessitates the pressing demand for new classes of anti-MRSA drugs. Bacterial gyrase targeted therapeutics are unique strategies to overcome cross-resistance as they are present only in bacteria and absent in higher eukaryotes. The GyrB subunit is essential for the catalytic functions of the bacterial enzyme DNA Gyrase, thereby constituting a promising druggable target. The current study performed a structure-based virtual screening to designing GyrB target-specific candidate molecules. The de novo ligand design of novel hit molecules was performed using a rhodanine scaffold. Through a systematic in silico screening process, the hit molecules were screened for their synthetic accessibility, drug likeliness and pharmacokinetics properties in addition to its target specific interactions. Of the total 374 hit molecules obtained through de novo ligand design, qsl-304 emerged as the most promising ligand. qsl-304 was synthesized through a one-step chemical synthesis procedure, and the in vitro activity was proven, with an IC50 of 31.23 g/mL against the novobiocin resistant clinical isolate of Staphylococcus aureus sa-P2003. Further studies on time-kill kinetics showed the bacteriostatic nature with the diminished recurrence of resistance.

microbiology↗