Intravenous BCG Vaccination of Diversity Outbred Mice Results in Moderately Enhanced Protection against Challenge with Mycobacterium tuberculosis Compared to Intradermal Vaccination.

Tuberculosis is still the leading cause of death globally from any infectious disease, despite the widespread use of the live attenuated vaccine Bacille Calmette Guerin (BCG). While BCG has some efficacy against disseminated TB disease in children, protection wanes into adulthood resulting in over 1.8 million TB deaths per year. This has led to efforts to develop novel vaccine candidates that either replace or boost BCG, as well as to test novel delivery mechanisms to enhance BCG's efficacy. Traditional BCG vaccination is performed as an intradermal (ID) injection but delivering BCG by an alternate route may enhance the depth and breadth of protection. Previously, we demonstrated that phenotypically and genotypically disparate Diversity Outbred (DO) mice have heterogenous responses to M. tuberculosis challenge following intradermal BCG vaccination. Here, we utilize DO mice to examine BCG-induced protection when BCG is delivered systemically via intravenous (IV) administration. We find that DO mice vaccinated with IV BCG had a greater distribution of BCG throughout their organs compared to ID-vaccinated animals. However, compared to ID-vaccinated mice, M. tuberculosis burdens in lungs and spleens were not significantly reduced in animals vaccinated with BCG IV, nor was lung inflammation significantly altered. Nonetheless, DO mice that received BCG IV had increased survival over those vaccinated by the traditional ID route. Thus, our results suggest that delivering BCG by the alternate IV route enhances protection as detected in this diverse small animal model.

A reflection on noncognitive factors affecting spatial cognitive testing: Examples from nonmodel species.

Probing for spatial cognitive processes in model rodent species has a long history in the psychological literature, with well-established protocols and paradigms successfully revealing the mechanisms underlying spatial learning and memory. There has also been much interest in examining the ecological and evolutionary context of spatial cognition, with a focus on how selection has molded spatial cognitive abilities in nonmodel species, how spatial cognitive traits vary across species, the neural mechanisms underlying spatial cognitive abilities, and the fitness outcomes of spatial cognition. Behavioral ecologists have been able to take advantage of paradigms from experimental psychology's rich history of spatial cognitive testing for use in nonmodel species. However, as the field advances, it is important to highlight noncognitive factors that can impact performance on spatial cognitive tasks (e.g., motivation to perform the task, switching navigational strategies, variation across protocols, ecological relevance of the task), as these factors may explain discrepancies in findings among some studies. This review highlights how these noncognitive factors can differentially modulate performance on spatial cognitive tests in different nonmodel species. Accounting for these factors when creating protocols and paradigms allows for a more nuanced approach with more explanatory power when probing for spatial cognitive abilities in nonmodel species. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Assessing Spatial Learning and Memory in Small Squamate Reptiles.

Clinical research has leveraged a variety of paradigms to assess cognitive decline, commonly targeting spatial learning and memory abilities. However, interest in the cognitive processes of nonmodel species, typically within an ecological context, has also become an emerging field of study. In particular, interest in the cognitive processes in reptiles is growing although experimental studies on reptilian cognition are sparse. The few reptilian studies that have experimentally tested for spatial learning and memory have used rodent paradigms modified for use in reptiles. However, ecologically important aspects of the physiology and behavior of this taxonomic group must be taken into account when testing for spatially based cognition. Here, we describe modifications of the dry land Barnes maze and associated testing protocol that can improve performance when probing for spatial learning and memory ability in small squamate reptiles. The described paradigm and procedures were successfully used with male side-blotched lizards (Uta stansburiana), demonstrating that spatial learning and memory can be assessed in this taxonomic group with an ecologically relevant apparatus and protocol.

Seasonal infection rates of Batrachochytrium dendrobatidis in populations of northern green frog Lithobates clamitans melanota tadpoles.

Few studies have documented seasonal variation of Batrachochytrium dendrobatidis (Bd) infection rates in larval amphibians. We identified 4 natural populations of northern green frogs Lithobates clamitans melanota in Pennsylvania (USA) that contained Bd-infected tadpoles during post-wintering collections in May and June, after hibernating tadpoles had overwintered in wetlands. However, we failed to detect infected tadpoles at those wetlands when pre-wintering collections were made in late July through early September. We observed 2 cohorts of tadpoles that appeared to lack Bd-infected individuals in pre-wintering collections, yet contained Bd-infected individuals the following spring. We also observed 4 cohorts of pre-wintering tadpoles that were Bd-free, even though post-wintering tadpoles collected earlier in the year were infected with Bd. Our results suggest that tadpoles either reduce Bd infections during the summer months, and/or infections proliferate sometime prior to (or shortly after) tadpoles emerge from hibernation. It is unlikely that pre-wintering tadpoles were too small to detect Bd zoospores because (1) there was no correlation between Bd zoospore levels and tadpole size or stage, and (2) size was not a significant predictor of infection status. These results suggest that, while sampling larvae can be an effective means of collecting large sample sizes, investigators in our Mid-Atlantic region should conduct sampling by early summer to maximize the chances of detecting Bd. Further research is warranted to determine whether wetland topography and warm, shallow microhabitats within wetlands contribute to a population's ability to drastically reduce Bd prevalence prior to overwintering at ponds.