Objectives/Goals: Short-chain fatty acids (SCFAs) exert protective effects against calcium oxalate (CaOx) urinary stone formation in experimental rodent models, yet these effects are not understood in natural stone formers. This study will define the impact of SCFAs on stone risk factors along the gut–kidney axis in a natural canine model of CaOx stone disease. Methods/Study Population: A randomized, placebo-controlled, clinical trial will be performed using a crossover study design. Twenty dogs that are natural CaOx stone formers will be fed a standardized diet and randomized to receive either a daily prebiotic fiber (inulin) that stimulates SCFA production or a placebo. We will perform fecal shotgun metagenomics and SCFA quantification before and after each intervention (four timepoints) to identify how inulin and SCFAs enrich or deplete pathways relevant to stone formation within the gut microbiome. RT-qPCR will be performed to determine the effects of SCFAs on intestinal oxalate transporter gene expression (SLC26A3 and SLC26A6). At each timepoint, urinary shotgun metagenomics and quantification of urine biochemical profiles used to predict stone risk will also be performed. Results/Anticipated Results: We anticipate that prebiotic stimulation of SCFAs with inulin will reduce stone risk factors along the gut–urinary axis in a natural canine model of urinary stone disease. Specifically, we anticipate that prebiotic stimulation of SCFAs will 1) modify gut and urinary microbial communities to promote pathways considered protective against stone formation, 2) alter the expression of oxalate transporters (SLC26A3, SLC26A6) to reduce net oxalate absorption, and 3) reduce stone-promoting metabolites (e.g., oxalate) in the urine. Discussion/Significance of Impact: By defining the impact of prebiotic fibers and SCFAs on the gut–urinary axis in a natural animal model of CaOx urolithiasis, we will lay the foundation for novel nutritional strategies to prevent CaOx stone disease in both humans and animals.

A 15-year-old male presented with vasovagal syncope and troponin leak 4 days after his second COVID-19 vaccine. Based on initial diagnostic work-up, he was thought to have COVID-19 vaccine-associated myocarditis. His cardiac dysfunction persisted and further work-up including genetic evaluation and serial MRI studies later confirmed a diagnosis of arrhythmogenic cardiomyopathy. This is a unique case of an incorrect diagnosis based on timing and context of vaccine-related myocarditis. Reports of mild and self-limited myocarditis post-COVID-19 vaccination may cause vaccine hesitancy among the public, and so case reports such as this one show the importance of discerning underlying conditions amongst rare COVID-19 vaccination complications.

OBJECTIVES/GOALS: This study proposes a pragmatic approach for tracking institutional changes in research teamwork and productivity in real time using common institutional electronic databases such as eCV and grant management systems. Dissemination of this approach could provide a standard metric for comparing teamwork productivity across different programs. METHODS/STUDY POPULATION: This study tracks research teamwork and productivity using commonly available institutional electronic databases such as eCV and grant management systems. We tested several definitions of interdisciplinary collaborations based on number of collaborations and their fields of discipline. Publication characteristics were compared by faculty seniority and appointment type using non-parametric Wilcoxon Rank Sum Test (p RESULTS/ANTICIPATED RESULTS: Interdisciplinary grants constitute 24% of all grants but the trend has significantly increased over the last five years. Tenure track faculty collaborated with more organizations (3.5, SD 2.5 vs 2.3, SD 1.1, p DISCUSSION/SIGNIFICANCE: This study provides empirical evidence of the benefits of interdisciplinary collaboration in research and identifies an important role that senior faculty may be playing in creating the culture of interdisciplinary teamwork. More research is needed to improve efficiency of interdisciplinary collaborations.

Praziquantel (PZQ) remains the only drug of choice for the treatment of schistosomiasis, caused by parasitic flatworms. The widespread use of PZQ in schistosomiasis endemic areas for about four decades raises concerns about the emergence of resistance of Schistosoma spp. to PZQ under drug selection pressure. This reinforces the urgency in finding alternative therapeutic options that could replace or complement PZQ. We explored the potential of medicinal plants commonly used by indigenes in Kenya for the treatment of various ailments including malaria, pneumonia, and diarrhoea for their antischistosomal properties. Employing the Soxhlet extraction method with different solvents, seven medicinal plants Artemisia annua, Ajuga remota, Bredilia micranta, Cordia africana, Physalis peruviana, Prunus africana and Senna didymobotrya were extracted. Qualitative phytochemical screening was performed to determine the presence of various phytochemicals in the plant extracts. Extracts were tested against Schistosoma mansoni newly transformed schistosomula (NTS) and adult worms and the schistosomicidal activity was determined by using the adenosine triphosphate quantitation assay. Phytochemical analysis of the extracts showed different classes of compounds such as alkaloids, tannins, terpenes, etc., in plant extracts active against S. mansoni worms. Seven extracts out of 22 resulted in <20% viability against NTS in 24 h at 100 μg/ml. Five of the extracts with inhibitory activity against NTS showed >69.7% and ≥72.4% reduction in viability against adult worms after exposure for 24 and 48 h, respectively. This study provides encouraging preliminary evidence that extracts of Kenyan medicinal plants deserve further study as potential alternative therapeutics that may form the basis for the development of the new treatments for schistosomiasis.

From 2014 to 2020, we compiled radiocarbon ages from the lower 48 states, creating a database of more than 100,000 archaeological, geological, and paleontological ages that will be freely available to researchers through the Canadian Archaeological Radiocarbon Database. Here, we discuss the process used to compile ages, general characteristics of the database, and lessons learned from this exercise in “big data” compilation.

The foundation of W. Matthews Grant's project in Free Will and God's Universal Causality is his Non-Occasionalist version of Divine Universal Causality (NODUC), which affirms the traditional concurrentist idea that God and secondary causes cooperate non-superfluously in such a way that they both produce the entire effect. Grant defends NODUC's concurrentist account by responding to ‘The Metaphysical Objection’, which alleges that concurrentism places an inconsistent set of demands upon secondary causes. I argue that Grant's responses to that objection are unconvincing, and thus, he fails to demonstrate that NODUC is a stable foundation for the rest of his project.

Several recent formulations of Rule Consequentialism (RC) have broken with the consensus that RC should be formulated in terms of code acceptance, claiming instead that RC should focus on the consequences of codes' being taught. I begin this article with an examination of the standard case for acceptance formulations. In addition to depending on the mistaken assumption that compliance and acceptance formulations are the only options, the standard case claims advantages for acceptance formulations that, upon closer examination, favor teaching formulations. In the remainder of the article, I defend this new teaching-centered approach against some recent criticisms. I argue that preoccupation with the somewhat technical problem of identifying the best criterion for making choices under conditions of uncertainty has distracted rule consequentialists from paying more careful attention to the advantages and disadvantages that result from decisions concerning where they locate RC's stipulated assumptions within the theory.

Colonialism came late to northern Guatemala. The Spanish began to establish missions in the Peten Lakes region in the early 1700s, nearly 200 years after initial contact with the Mayas. Excavations in 2011–2012 at the Mission San Bernabé revealed European goods, nonnative animal species, and burial patterns that marked a new lifestyle. Who lived at the Mission San Bernabé, and where did they come from? The Spanish resettled indigenous populations to facilitate the colonization process; however, isotopic data are inconsistent with large population movements. Instead, strontium and oxygen isotope values in the tooth enamel and bones of individuals buried at the mission suggest a mostly local population. The data suggest in-migration from Belize, a region under nominal Spanish control, but with pre-Hispanic ties to the Peten. Changes did not come from migrants crossing a border; instead, the border itself moved and brought the colonial world to the Peten Mayas.

OBJECTIVES/SPECIFIC AIMS: We aimed to develop an assay to measure new protein synthesis after Antisense Oligonucleotide treatment, which we hypothesized to be the earliest biochemical identification of RNA-targeting therapy efficacy. METHODS/STUDY POPULATION: We treated 2 transgenic animal models expressing proteins implicated in neurodegenerative disease: human tau protein (hTau) and human superoxide dismutase 1 (hSOD1), with ASO against these mRNA transcripts. Animals received isotope-labeled 13C6-Leucine via drinking water to label newly synthesized proteins. We assayed target protein synthesis and concentration after ASO treatment to determine the earliest identification of ASO target engagement. RESULTS/ANTICIPATED RESULTS: hTau ASO treatment in transgenic mice lowered hTau protein concentration 23 days post-treatment in cortex (95% CI: 0.05%–64.0% reduction). In the same tissue, we observed lowering of hTau protein synthesis as early as 13 days (95% CI: 29.4%–123%). In hSOD1 transgenic rats, we observed lowering of 13C6-leucine-labeled hSOD1 in the cerebrospinal fluid 30 days after ASO treatment compared with inactive ASO control (95% CI: 12.0%–48.4%). DISCUSSION/SIGNIFICANCE OF IMPACT: In progressive neurodegenerative diseases, it is crucial to develop measurements that identify treatment efficacy early to improve patient outcomes. These data support the use of stable isotope labeling of amino acids to measure new protein synthesis as an early pharmacodynamics measurement for therapies that target RNA and inhibit the translation of proteins.

Field studies on time of emergence, influence of planting date on growth and reproduction, and winter survival of rhizomes were conducted on sorghum-almum grown in corn and crop-free environments. In 1985, peak emergence of sorghum-almum occurred during early May in crop-free plots and mid-May in corn. In 1986, two peaks of emergence, one in early June and one in late June, were noted in both crop-free and corn plots. Emergence after mid-July was 4% or less of the total emerged in 1985, and no sorghum-almum emerged after mid-July in 1986. In planting date studies, sorghum-almum was seeded alone or in corn at 2-week intervals. Corn competition reduced sorghum-almum shoot, rhizome, and root growth at all planting dates. Maximum sorghum-almum seed production was 43 110 seed/plant when grown without competition but only 1050 seed/plant when grown with corn competition. When grown with corn competition, no seed developed on sorghum-almum seeded 6 or more weeks (mid-June or later) after corn planting. Shoot dry weight of sorghum-almum grown with corn competition was 3 g/plant or less for plants seeded 4 or more weeks (early June or later) after corn planting. Therefore, controlling sorghum-almum in corn through mid-June should prevent seed production and corn yield losses due to sorghum-almum competition. Rhizomes produced by sorghum-almum grown alone or with corn competition did not survive the winter; therefore, in Minnesota, sorghum-almum survival from one growing season to the next depends on seed production.