Predicting the fine-scale spatial distribution of zoonotic reservoirs using computer vision.

Zoonotic diseases threaten human health worldwide and are often associated with anthropogenic disturbance. Predicting how disturbance influences spillover risk is critical for effective disease intervention but difficult to achieve at fine spatial scales. Here, we develop a method that learns the spatial distribution of a reservoir species from aerial imagery.

Designing transmissible viral vaccines for evolutionary robustness and maximum efficiency.

The danger posed by emerging infectious diseases necessitates the development of new tools that can mitigate the risk of animal pathogens spilling over into the human population. One promising approach is the development of recombinant viral vaccines that are transmissible, and thus capable of self-dissemination through hard to reach populations of wild animals. Indeed, mathematical models demonstrate that transmissible vaccines can greatly reduce the effort required to control the spread of zoonotic pathogens in their animal reservoirs, thereby limiting the chances of human infection.

Suppressing evolution in genetically engineered systems through repeated supplementation.

Genetically engineered organisms are prone to evolve in response to the engineering. This evolution is often undesirable and can negatively affect the purpose of the engineering. Methods that maintain the stability of engineered genomes are therefore critical to the successful design and use of genetically engineered organisms.

Bridging the gap: Using reservoir ecology and human serosurveys to estimate Lassa virus spillover in West Africa.

Forecasting the risk of pathogen spillover from reservoir populations of wild or domestic animals is essential for the effective deployment of interventions such as wildlife vaccination or culling. Due to the sporadic nature of spillover events and limited availability of data, developing and validating robust, spatially explicit, predictions is challenging. Recent efforts have begun to make progress in this direction by capitalizing on machine learning methodologies.

Westward range expansion from middle latitudes explains the Mississippi River discontinuity in a forest herb of eastern North America.

It is often expected that temperate plants have expanded their geographical ranges northward from primarily southern refugia. Evidence for this hypothesis is mixed in eastern North American species, and there is increasing support for colonization from middle latitudes. We studied genome-wide patterns of variation in RADseq loci to test hypotheses concerning range expansion in a North American forest herb (Campanula americana).

Bayesian estimation of Lassa virus epidemiological parameters: Implications for spillover prevention using wildlife vaccination.

Lassa virus is a significant burden on human health throughout its endemic region in West Africa, with most human infections the result of spillover from the primary rodent reservoir of the virus, the natal multimammate mouse, M. natalensis. Here we develop a Bayesian methodology for estimating epidemiological parameters of Lassa virus within its rodent reservoir and for generating probabilistic predictions for the efficacy of rodent vaccination programs.

Selfing ability and drift load evolve with range expansion.

Colonization at expanding range edges often involves few founders, reducing effective population size. This process can promote the evolution of self-fertilization, but implicating historical processes as drivers of trait evolution is often difficult and requires an explicit model of biogeographic history. In plants, contemporary limits to outcrossing are often invoked as evolutionary drivers of self-fertilization, but historical expansions may shape mating system diversity, with leading-edge populations evolving elevated selfing ability.

Bottlenecks and inbreeding depression in autotetraploids.

Inbreeding depression is dependent on the ploidy of populations and can inhibit the evolution of selfing. While polyploids should generally harbor less inbreeding depression than diploids at equilibrium, it has been unclear whether this pattern holds in non-equilibrium conditions following bottlenecks. We use stochastic individual-based simulations to determine the effects of population bottlenecks on inbreeding depression in diploids and autotetraploids, in addition to cases where neo-autotetraploids form from the union of unreduced gametes.

Costs of selfing prevent the spread of a self-compatibility mutation that causes reproductive assurance.

In flowering plants, shifts from outcrossing to partial or complete self-fertilization have occurred independently thousands of times, yet the underlying adaptive processes are difficult to discern. Selfing's ability to provide reproductive assurance when pollination is uncertain is an oft-cited ecological explanation for its evolution, but this benefit may be outweighed by costs diminishing its selective advantage over outcrossing. We directly studied the fitness effects of a self-compatibility mutation that was backcrossed into a self-incompatible (SI) population of Leavenworthia alabamica, illuminating the direction and magnitude of selection on the mating-system modifier.

Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition--I. Synthesis, structure-activity relationship, and evaluation of substituted omega-phenyl-omega-(3-pyridyl)alkenoic acids.

A series of arylsulfonamido-substituted omega-phenyl-omega-(3-pyridyl)alkenoic acids were synthesized and evaluated in vitro for their ability to act as both a thromboxane A2 receptor antagonist (TRA) and thromboxane synthase inhibitor (TSI). Variations of alkenoic acid chain length, olefin geometry, substituent effect on the benzenesulfonamido group, and conformational flexibility of the substituted arylsulfonamido group were examined. Among the various substituents, iodo-substitution gave the most potent compound.

Dissociation of immunosuppression by chlorpromazine and trifluoperazine from pharmacologic activities as dopamine antagonists.

Neuroleptic compounds may affect the immune system through a variety of mechanisms. Most possess a complex pharmacology, which makes specific, causal relationships difficult to discern. In this study, a series of experiments was performed to examine the effects of dopamine antagonists on a battery of immunologic parameters.

Interleukin 1-induced pathophysiology: induction of cytokines, development of histopathologic changes, and immunopharmacologic intervention.

In this report, we describe a murine system in which treatment with recombinant human interleukin 1 (IL-1) induced an acute lethal state with pathologic changes similar to septic shock at high doses and development of arthritic and other tissue changes following more prolonged treatment with lower doses. We have demonstrated that both recombinant human interleukin 1 alpha and recombinant human interleukin 1 beta could be administered to an endotoxin hyporesponsive strain, C3H/HeJ, and produce these pathologic changes. Induction of tumor necrosis factor (TNF) and colony-stimulating factor activity was noted.

Neuroendocrine regulation of in vivo cytokine production and effects: I. In vivo regulatory networks involving the neuroendocrine system, interleukin-1 and tumor necrosis factor-alpha.

We have investigated the in vivo regulatory network involving the neuroendocrine system, interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF). Adrenalectomy or hypophysectomy shifted the sensitivity curve to lipopolysaccharide (LPS)-induced lethal shock as well as TNF- and IL-1-induced deaths. Serum levels of IL-1 or TNF were altered in adrenalectomized or hypophysectomized mice following in vivo stimulation with LPS when compared to appropriate sham-operated control mice.

Interleukin-2 induced systemic toxicity: induction of mediators and immunopharmacologic intervention.

Interleukin-2 has been tested as an anti-cancer agent, either alone or in combination with immune cells, but severe dose limiting adverse toxic effects have been observed. Because the pathogenesis of the toxicity has remained uncharacterized, it has not been possible to determine whether the therapeutic and the toxic events could be separated. We have examined immunopharmacologic regulation of IL2 induced mediator induction and toxicity syndrome and have compared this data with our earlier information on IL2 enhancement of immune function in murine systems.

In vivo effects of recombinant human interleukin 2 on antitumor and antiviral natural immunity in induced or natural murine immunodeficiency states.

We have examined the ability of in vivo treatment of mice with recombinant interleukin 2 (rIL-2) to affect natural immunity measured against tumor (YAC-1) or virally infected (herpes simplex type 1) target cells. rIL-2 treatment leads to significant increases in natural killer/lymphocyte-activated killer (NK/LAK) function and spleen cells recovered. This effect is dose dependent and strain related.

Isolation of several peptides with relaxin activity.

When a relaxin preparation was subjected to counter-current distribution for 355 transfers in a butanol-trichloroacetic acid system, significant biological activity was found over a band appreciably wider than was expected for a single component. By refractionation of the active band, three peptides with relaxin activity were isolated.