The gut microbiome is impacted by certain types of dietary fibre. However, the type, duration and dose needed to elicit gut microbial changes and whether these changes also influence microbial metabolites remain unclear. This study investigated the effects of supplementing healthy participants with two types of non-digestible carbohydrates (resistant starch (RS) and polydextrose (PD)) on the stool microbiota and microbial metabolite concentrations in plasma, stool and urine, as secondary outcomes in the Dietary Intervention Stem Cells and Colorectal Cancer (DISC) Study. The DISC study was a double-blind, randomised controlled trial that supplemented healthy participants with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design. DNA was extracted from stool samples collected pre- and post-intervention, and V4 16S rRNA gene sequencing was used to profile the gut microbiota. Metabolite concentrations were measured in stool, plasma and urine by high-performance liquid chromatography. A total of fifty-eight participants with paired samples available were included. After 50 d, no effects of RS or PD were detected on composition of the gut microbiota diversity (alpha- and beta-diversity), on genus relative abundance or on metabolite concentrations. However, Drichlet’s multinomial mixture clustering-based approach suggests that some participants changed microbial enterotype post-intervention. The gut microbiota and fecal, plasma and urinary microbial metabolites were stable in response to a 50-d fibre intervention in middle-aged adults. Larger and longer studies, including those which explore the effects of specific fibre sub-types, may be required to determine the relationships between fibre intake, the gut microbiome and host health.

OBJECTIVES/GOALS: To demonstrate a successful example of clinical and translational research at a busy veterinary teaching hospital and highlight a collaborative effort in Comparative Oncology between the University of Florida’s (UF) Colleges of Medicine and Veterinary Medicine. METHODS/STUDY POPULATION: The UF College of Veterinary Medicine (CVM) is a full-time teaching hospital with multiple departments actively recruiting patients for clinical trials. These departments include but are not limited to Oncology, Internal Medicine, Dermatology, Cardiology, and Emergency and Critical Care. The Oncology department collaborates with the doctors at the UF Health Cancer Center (UFHCC) as part of a Comparative Oncology Initiative, which has many ongoing canine and feline trials focusing on immunotherapy. RESULTS/ANTICIPATED RESULTS: As of August 2023, there are 60 clinical trials actively recruiting and enrolling patients at the UF CVM. 57% of these trials are interventional studies, while the other 43% are observational studies. The UFHCC Comparative Oncology Initiative has successfully completed one clinical trial focusing on canine gliomas; has 4 clinical trials that are actively recruiting patients, and 6 trials that are opening for enrollment in the near future. These studies focus on osteosarcoma, melanoma, and squamous cell carcinoma. It is anticipated that with continued successful collaborations, more clinical trials will be possible, and new treatment options will become available for not only veterinary patients but human patients as well. DISCUSSION/SIGNIFICANCE: Clinical and translational research is an important part of veterinary medicine to further patient care. Due to ongoing collaborative efforts, not only veterinary patients but also human patients will benefit from the research being conducted at the UF CVM.

We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.

In the US Southwest and Northwest Mexico, people and turkeys (Meleagris gallopavo) have had a reciprocal relationship for millennia; turkeys supplied feathers, meat, and other resources, whereas people provided food, shelter, and care. To investigate how turkeys fit within subsistence, economic production, sociopolitical organization, and religious and ritual practice in the Mimbres Valley of southwestern New Mexico, we report on genetic (mtDNA) and stable isotope (δ13C, δ15N) data from turkeys recovered from Mimbres Classic period (AD 1000–1130) sites. Results indicate that Mimbres aviculturists had haplogroup H1 and H2 turkeys, and most ate maize-based diets similar to humans, but some ate nonmaize and mixed diets. We contextualize these data to other turkey studies from the northern Southwest and discuss how the human-turkey relationship began, the evidence for pens and restricting turkey movement, and the socioecological factors related to turkey management during the Classic period, particularly the challenges associated with providing maize to turkeys during times of environmental stress. This study has broad relevance to places where people managed wild, tame, and domestic animals, and we offer new insights into how prehispanic, small-scale, middle-range agricultural societies managed turkeys for ritual and utilitarian purposes.