The Magellanic Stream (MS), a tail of diffuse gas formed from tidal and ram pressure interactions between the Small and Large Magellanic Clouds (SMC and LMC) and the Halo of the Milky Way, is primarily composed of neutral atomic hydrogen (HI). The deficiency of dust and the diffuse nature of the present gas make molecular formation rare and difficult, but if present, could lead to regions potentially suitable for star formation, thereby allowing us to probe conditions of star formation similar to those at high redshifts. We search for $\text{HCO}^{+}$, HCN, HNC, and C$_2$H using the highest sensitivity observations of molecular absorption data from the Atacama Large Millimeter Array (ALMA) to trace these regions, comparing with HI archival data from the Galactic Arecibo L-Band Feed Array (GALFA) HI Survey and the Galactic All Sky Survey (GASS) to compare these environments in the MS to the HI column density threshold for molecular formation in the Milky Way. We also compare the line of sight locations with confirmed locations of stars, molecular hydrogen, and OI detections, though at higher sensitivities than the observations presented here.

We find no detections to a 3$\sigma$ significance, despite four sightlines having column densities surpassing the threshold for molecular formation in the diffuse regions of the Milky Way. Here we present our calculations for the upper limits of the column densities of each of these molecular absorption lines, ranging from $3 \times 10^{10}$ to $1 \times 10^{13}$ cm$^{-2}$. The non-detection of $\text{HCO}^{+}$ suggests that at least one of the following is true: (i) $X_{\text{HCO}^{+}{}, \mathrm{MS}}$ is significantly lower than the Milky Way value; (ii) that the widespread diffuse molecular gas observed by Rybarczyk (2022b, ApJ, 928, 79) in the Milky Way’s diffuse interstellar medium (ISM) does not have a direct analogue in the MS; (iii) the HI-to-$\text{H}_{2}$ transition occurs in the MS at a higher surface density in the MS than in the LMC or SMC; or (iv) molecular gas exists in the MS, but only in small, dense clumps.

Childhood obesity represents a significant global health concern and identifying its risk factors is crucial for developing intervention programs. Many “omics” factors associated with the risk of developing obesity have been identified, including genomic, microbiomic, and epigenomic factors. Here, using a sample of 48 infants, we investigated how the methylation profiles in cord blood and placenta at birth were associated with weight outcomes (specifically, conditional weight gain, body mass index, and weight-for-length ratio) at age six months. We characterized genome-wide DNA methylation profiles using the Illumina Infinium MethylationEpic chip, and incorporated information on child and maternal health, and various environmental factors into the analysis. We used regression analysis to identify genes with methylation profiles most predictive of infant weight outcomes, finding a total of 23 relevant genes in cord blood and 10 in placenta. Notably, in cord blood, the methylation profiles of three genes (PLIN4, UBE2F, and PPP1R16B) were associated with all three weight outcomes, which are also associated with weight outcomes in an independent cohort suggesting a strong relationship with weight trajectories in the first six months after birth. Additionally, we developed a Methylation Risk Score (MRS) that could be used to identify children most at risk for developing childhood obesity. While many of the genes identified by our analysis have been associated with weight-related traits (e.g., glucose metabolism, BMI, or hip-to-waist ratio) in previous genome-wide association and variant studies, our analysis implicated several others, whose involvement in the obesity phenotype should be evaluated in future functional investigations.

OBJECTIVES/GOALS: The Institute of Translational Health Science (ITHS) Remote Technologies for Research Reference Center (REMOTECH) aims to support researchers using remote technologies. Understanding barriers specifically for engagement of diverse populations is critical to improve equitable access and increase diverse participation in research. METHODS/STUDY POPULATION: We conducted semi-structured interviews with researchers (N=30) within the WWAMI (Washington, Wyoming, Alaska, Montana and Idaho) region, identified through participation in a previous survey as well as those known to have previously implemented remote technologies at ITHS institutions. We solicited specific concerns regarding equity, diversity, and inclusion (EDI) related to remote research participant recruitment, retention, and implementation, as well as outcomes and potential solutions. Interview transcripts were coded, summarized, and emerging themes were identified. RESULTS/ANTICIPATED RESULTS: The pandemic necessitated a shift to the use of remote research engagement strategies. Our interview findings show that researchers have a desire to: increase diversity through remote engagement options; decrease participant burden; and understand and include strategies that advance equity, diversity, and inclusion (EDI) efforts. While geographic diversity was positively impacted by the use of remote technologies, significant barriers and challenges currently exist in the use of remote technologies with respect to other types of diversity, for example access to technologies and limited financial resources. DISCUSSION/SIGNIFICANCE: Remote technologies in research could increase diversity, but interviewees shared barriers and challenges that prevent that from happening. Researchers would benefit from equity-oriented digital literacy resources to use with diverse populations. Such tools can also be used to guide study design/procedures, materials, and processes.

OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.

Maternal diet influences breast milk nutritional profile; however, it is unclear which nutrients and contaminants are particularly responsive to short- and long-term changes in maternal intake, and the impact of specific exclusion diets, such as vegan or vegetarian. This study systematically reviewed the literature on the effects of maternal nutrient intake, including exclusion diets, on both the nutrient and contaminant content of breast milk. The electronic databases, PubMed, CENTRAL, Web of Science and CINALH were systematically searched until 4 June 2023, with additionally searches of reference lists (PROSPERO, CRD42020221577). The quality of the studies was examined using Cochrane Risk of Bias tool and Newcastle–Ottawa scale. Eighty-eight studies (n 6577) met the search criteria. Due to high heterogeneity, meta-analysis was not possible. There was strong evidence of response to maternal intakes for DHA and EPA, vitamins A, E and K, iodine and Se in breast milk composition, some evidence of response for α-linolenic acid, B vitamins, vitamin C and D, ovalbumin, tyrosine and contaminants, and insufficient evidence to identify the effects arachidonic acid, Cu, Fe, Zn and choline. The paucity of evidence and high heterogeneity among studies reflects the need for more high-quality trials. However, this review identified the importance of maternal intake in the nutritional content of breast milk for a wide range of nutrients and supports the recommendation for supplementation of DHA and vitamin B12 for those on restrictive diets.

Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central haemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean age 66·0 (sd 4·1) years; BMI, 26·4 (sd 4·41) kg/m2; 41 % male) recruited as part of the Australian Research Council Longevity Intervention study. Flavonoid intake (i.e. flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption) was estimated from FFQ using the US Department of Agriculture food composition databases. Measures of central haemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP) and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each sd/d higher intake of anthocyanins ((sd 44·3) mg/d) was associated with significantly lower cDBP (−1·56 mmHg, 95 % CI −2·65, −0·48) and cMAP (−1·62 mmHg, 95 % CI −2·82, −0·41). Similarly, each sd/d higher intake of flavanones ((sd 19·5) mg/d) was associated with ~1 % lower cAIx (−0·93 %, 95 % CI −1·77, −0·09). These associations remained significant after additional adjustment for (1) a dietary quality score and (2) other major nutrients that may affect blood pressure or arterial stiffness (i.e. Na, K, Ca, Mg, n-3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central haemodynamics and arterial stiffness; these findings require corroboration in further research.