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.

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.

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.

Dietary patterns influence gut microbiota composition. To date, there has not been an assessment of diet and gut microbiota in Veterans, who have a history of unique environmental exposures, including military deployment, that may influence associations between diet and gut microbiota. Our aim was to characterise Veteran habitual dietary intake and quality, and to evaluate correlations between diet and gut microbiota. We administered Food Frequency Questionnaires (FFQs) and collected stool samples from 330 Veterans. FFQ data were used to generate Healthy Eating Indices (HEI) of dietary quality. Exploratory factor analysis was used to identify two dietary patterns we defined as “Western” and “Prudent.” Stool samples underwent 16S rRNA gene sequencing, and the resulting data were used to evaluate associations with dietary variables/indices. Analyses included linear regression of α-diversity, constrained analysis of principal coordinates of β-diversity, and multivariate association with linear models and Analysis of Composition of Microbiomes analyses of dietary factors and phylum- and genus-level taxa. There were no significant associations between dietary patterns or factors and α- or β-diversity. At the phylum level, increasing HEI scores were inversely associated with relative abundance of Actinobacteria, and added sugar was inversely associated with abundance of Verrucomicrobia. Veterans largely consumed a Western-style diet, characterised by poor adherence to nutritional guidelines.

SHEA endorses adhering to the recommendations by the CDC and ACIP for immunizations of all children and adults. All persons providing clinical care should be familiar with these recommendations and should routinely assess immunization compliance of their patients and strongly recommend all routine immunizations to patients. All healthcare personnel (HCP) should be immunized against vaccine-preventable diseases as recommended by the CDC/ACIP (unless immunity is demonstrated by another recommended method). SHEA endorses the policy that immunization should be a condition of employment or functioning (students, contract workers, volunteers, etc) at a healthcare facility. Only recognized medical contraindications should be accepted for not receiving recommended immunizations.

This study provides a morphological and phylogenetic characterization of two novel species of the order Haplosporida (Haplosporidium carcini n. sp., and H. cranc n. sp.) infecting the common shore crab Carcinus maenas collected at one location in Swansea Bay, South Wales, UK. Both parasites were observed in the haemolymph, gills and hepatopancreas. The prevalence of clinical infections (i.e. parasites seen directly in fresh haemolymph preparations) was low, at ~1%, whereas subclinical levels, detected by polymerase chain reaction, were slightly higher at ~2%. Although no spores were found in any of the infected crabs examined histologically (n = 334), the morphology of monokaryotic and dikaryotic unicellular stages of the parasites enabled differentiation between the two new species. Phylogenetic analyses of the new species based on the small subunit (SSU) rDNA gene placed H. cranc in a clade of otherwise uncharacterized environmental sequences from marine samples, and H. carcini in a clade with other crustacean-associated lineages.

Unlike most other countries, in the United States, subnational governments (states) have substantial authority over collective bargaining and union organization laws. Because states compete for business investment and union (dis)organization likely has spillover effects beyond state borders, weak unions in one state may affect union organization in other states. We examine how union decline in one state is associated with union decline in neighboring states, and whether the presence of prounion (left-leaning) governments may limit the spread of union decline. Examining a period of major union decline (1983-2014), we find that union weakness in one state is associated with union weakness in nearby states. We observe that Democratic power in Congress is associated with higher unionization rates, but that liberal state governments have been relatively powerless to stop union decline in this period. These findings have important implications for understanding the historical and contemporary weakness of American unions and for the future of union strength in the United States.

Species distribution models (SDMs) are statistical tools used to develop continuous predictions of species occurrence. ‘Integrated SDMs’ (ISDMs) are an elaboration of this approach with potential advantages that allow for the dual use of opportunistically collected presence-only data and site-occupancy data from planned surveys. These models also account for survey bias and imperfect detection through the use of a hierarchical modelling framework that separately estimates the species–environment response and detection process. This is particularly helpful for conservation applications and predictions for rare species, where data are often limited and prediction errors may have significant management consequences. Despite this potential importance, ISDMs remain largely untested under a variety of scenarios. We performed an exploration of key modelling decisions and assumptions on an ISDM using the endangered Baird’s tapir (Tapirus bairdii) as a test species. We found that site area had the strongest effect on the magnitude of population estimates and underlying intensity surface and was driven by estimates of model intercepts. Selecting a site area that accounted for the individual movements of the species within an average home range led to population estimates that coincided with expert estimates. ISDMs that do not account for the individual movements of species will likely lead to less accurate estimates of species intensity (number of individuals per unit area) and thus overall population estimates. This bias could be severe and highly detrimental to conservation actions if uninformed ISDMs are used to estimate global populations of threatened and data-deficient species, particularly those that lack natural history and movement information. However, the ISDM was consistently the most accurate model compared to other approaches, which demonstrates the importance of this new modelling framework and the ability to combine opportunistic data with systematic survey data. Thus, we recommend researchers use ISDMs with conservative movement information when estimating population sizes of rare and data-deficient species. ISDMs could be improved by using a similar parameterization to spatial capture–recapture models that explicitly incorporate animal movement as a model parameter, which would further remove the need for spatial subsampling prior to implementation.

Camera trap surveys are a non-invasive way to monitor wildlife populations. Although most often used to study medium- and large-sized mammals, camera traps also detect non-target species. These detections provide useful ecological information on little-known species, but such data usually remain unanalysed. We used detections from camera-trapping surveys of native carnivores and small mammals to examine distribution patterns and occupancy trends of little-known ground-dwelling rainforest birds at seven sites across the Masoala-Makira protected area complex in north-eastern Madagascar. We obtained 4,083 detections of 28 bird species over 18,056 trap nights from 200 to 2013. We estimated occupancy across the Masoala-Makira protected area complex (hereafter, landscape occupancy) and annual trends in occupancy at three resurveyed sites for five commonly observed species. Landscape occupancy across Masoala-Makira ranged from 0.75 (SE 0.09; Madagascar Magpie-robin Copsychus albospecularis) to 0.25 (SE 0.06; Scaly Ground-roller Geobiastes squamiger). Ground-dwelling forest bird occupancy was similar at forest sites that ranged from intact to fully degraded; however, three species were detected less often at sites with high feral cat trap success. Nearly half of all focal species showed declines in annual occupancy probability at one resurveyed site (S02) from 2008 to 2013. The declines in ground-dwelling bird occupancy could have community-wide consequences as birds provide ecosystem services such as seed dispersal and pest regulation. We suggest immediate conservation measures—such as feral cat removal—be implemented to protect ground-dwelling forest birds and other threatened taxa across this landscape.

This article outlines a new method for surveys to study elections and voter attitudes. Pre-election surveys often suffer from an inability to identify and survey the likely electorate for the upcoming election. We propose a new and inexpensive method to conduct representative surveys of the electorate. We demonstrate the performance of our method in producing a representative sample of the future electorate that can be used to study campaign dynamics and many other issues. We compare pre-election outcome forecasts to election outcomes in seven primary and general election surveys conducted prior to the 2008 and 2010 primary and general elections in three states. The results indicate that the methodology produces representative samples, including in low-turnout elections such as primaries where traditional methods have difficulty consistently sampling the electorate. This new methodology combines Probability Proportional to Size (PPS) sampling, mailed invitation letters, and online administration of the questionnaire. The PPS sample is drawn based on a model employing variables from the publicly available voter file to produce a probability of voting score for each individual voter. The proposed method provides researchers a valuable tool to study the attitudes of the voting public.