Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart. However, the impact of this reactivation on the regulatory landscape in heart disease is unclear. Here, we use RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from up to 26 healthy controls, 18 individuals with idiopathic dilated cardiomyopathy (DCM), and five fetal hearts.
View Article and Find Full Text PDFSpinach (Spinacia oleracea L.) is a member of the Caryophyllales family, a basal eudicot asterid that consists of sugar beet (Beta vulgaris L. subsp.
View Article and Find Full Text PDFSafety-net clinic patients are at risk for food insecurity, which is associated with poor diet quality and negative health outcomes. Research on the impact of interventions addressing food insecurity in health care settings is limited. The primary aim of this study was to determine the preliminary effectiveness of Community-Supported Agriculture (CSA) Partnerships for Health, a 23 week grant-subsidized CSA program, in improving dietary behaviors, self-efficacy to eat vegetables, food security, and overall health among safety-net clinic patients.
View Article and Find Full Text PDFTribal communities in the United States face disparities to accessing healthy foods including high-quality produce. A six-week fresh fruit and vegetable (FV) dietary intervention, , was co-designed with a Community Advisory Board of local food and nutrition stakeholders on the Flathead Reservation of the Confederated Salish and Kootenai Tribes in Montana. was implemented as a pilot study with low-income participants ( = 19) enrolled in the Food Distribution Program on Indian Reservations toward improving dietary quality and perceptions of well-being.
View Article and Find Full Text PDFEnhancers are important non-coding elements, but they have traditionally been hard to characterize experimentally. The development of massively parallel assays allows the characterization of large numbers of enhancers for the first time. Here, we developed a framework using Drosophila STARR-seq to create shape-matching filters based on meta-profiles of epigenetic features.
View Article and Find Full Text PDFThe Encyclopedia of DNA Elements (ENCODE) project has established a genomic resource for mammalian development, profiling a diverse panel of mouse tissues at 8 developmental stages from 10.5 days after conception until birth, including transcriptomes, methylomes and chromatin states. Here we systematically examined the state and accessibility of chromatin in the developing mouse fetus.
View Article and Find Full Text PDFThe National Early Care and Education Learning Collaboratives Project (ECELC) was a multistate intervention that was highly effective in implementing best practices for healthy eating physical activity (HEPA) in early care and education (ECE) programs across the USA. The ECELC included didactic in-person learning sessions, technical assistance, and self-assessment-guided action planning. This study aimed to describe the effectiveness of adaptions to the self-assessments, learning sessions, and overall support, and also aimed to compare the effectiveness of each to the Original ECELC Model, when applicable.
View Article and Find Full Text PDFDiet-related chronic disease is among the most pressing public health issues and represents a health disparity among Native American communities. A community-based participatory approach was taken to evaluate dietary quality of adult residents of the Flathead Reservation of the Confederated Salish & Kootenai Tribes in Montana (the Flathead Nation). A survey was administered to collect basic demographic information and food security status (N = 80).
View Article and Find Full Text PDFPurpose And Objectives: Embedding healthy eating and physical activity best practices in early care and education settings is important for instilling healthy behaviors early in life. A collaborative partnership between Nemours Children's Health System and the Centers for Disease Control and Prevention was created to implement the National Early Care and Education Learning Collaboratives Project (ECELC) in childcare settings in 10 states. We measured improvement at the program level by the self-reported number of best practices implemented related to healthy eating and physical activity.
View Article and Find Full Text PDFObjective: To describe low-income parents' and caregivers' perceptions of the Cooking Matters Mobile Application (CM App) meal planning and preparation features.
Design: Explanatory mixed-methods design where data were gathered via online surveys based on the Theory of Planned Behaviour and the Theory of Reasoned Action, followed by telephone interviews.
Setting: CM App, a mobile phone-based resource geared towards low-income parents and caregivers of young children (pregnancy/infant to age 5 years) for meal planning and preparation, with features based on skills taught in the Cooking Matters course: recipes, shopping list and meal planning.
A curvilinear relationship exists between physical activity (PA) and dietary energy intake (EI), which is reduced in moderately active when compared to inactive and highly active individuals, but the impact of PA on eating patterns remains poorly understood. Our goal was to establish the relationship between PA and intake of foods with varying energy and nutrient density. Data from the 2009-2010 United States National Health and Nutrition Examination Survey were used to include a Dietary Screener Questionnaire for estimated intakes of added sugar, fruits and vegetables, whole grains, fiber, and dairy.
View Article and Find Full Text PDFCities are increasingly home to the world's population. Creating healthy and vibrant cities is one way to positively contribute to the health of populations. Parks and green spaces in cities contribute many health benefits.
View Article and Find Full Text PDFThe SK-BR-3 cell line is one of the most important models for HER2+ breast cancers, which affect one in five breast cancer patients. SK-BR-3 is known to be highly rearranged, although much of the variation is in complex and repetitive regions that may be underreported. Addressing this, we sequenced SK-BR-3 using long-read single molecule sequencing from Pacific Biosciences and develop one of the most detailed maps of structural variations (SVs) in a cancer genome available, with nearly 20,000 variants present, most of which were missed by short-read sequencing.
View Article and Find Full Text PDFDistant-acting tissue-specific enhancers, which regulate gene expression, vastly outnumber protein-coding genes in mammalian genomes, but the functional importance of this regulatory complexity remains unclear. Here we show that the pervasive presence of multiple enhancers with similar activities near the same gene confers phenotypic robustness to loss-of-function mutations in individual enhancers. We used genome editing to create 23 mouse deletion lines and inter-crosses, including both single and combinatorial enhancer deletions at seven distinct loci required for limb development.
View Article and Find Full Text PDFNon-coding "ultraconserved" regions containing hundreds of consecutive bases of perfect sequence conservation across mammalian genomes can function as distant-acting enhancers. However, initial deletion studies in mice revealed that loss of such extraordinarily constrained sequences had no immediate impact on viability. Here, we show that ultraconserved enhancers are required for normal development.
View Article and Find Full Text PDFEpigenomic mapping of enhancer-associated chromatin modifications facilitates the genome-wide discovery of tissue-specific enhancers in vivo. However, reliance on single chromatin marks leads to high rates of false-positive predictions. More sophisticated, integrative methods have been described, but commonly suffer from limited accessibility to the resulting predictions and reduced biological interpretability.
View Article and Find Full Text PDFThe contributions of coding mutations to tumorigenesis are relatively well known; however, little is known about somatic alterations in noncoding DNA. Here we describe GECCO (Genomic Enrichment Computational Clustering Operation) to analyze somatic noncoding alterations in 308 pancreatic ductal adenocarcinomas (PDAs) and identify commonly mutated regulatory regions. We find recurrent noncoding mutations to be enriched in PDA pathways, including axon guidance and cell adhesion, and newly identified processes, including transcription and homeobox genes.
View Article and Find Full Text PDFMany lines of evidence have indicated that both genetic and non-genetic determinants can contribute to intra-tumor heterogeneity and influence cancer outcomes. Among the best described sub-population of cancer cells generated by non-genetic mechanisms are cells characterized by a CD44+/CD24- cell surface marker profile. Here, we report that human CD44+/CD24- cancer cells are genetically highly unstable because of intrinsic defects in their DNA-repair capabilities.
View Article and Find Full Text PDFThe evolution of body shape is thought to be tightly coupled to changes in regulatory sequences, but specific molecular events associated with major morphological transitions in vertebrates have remained elusive. We identified snake-specific sequence changes within an otherwise highly conserved long-range limb enhancer of Sonic hedgehog (Shh). Transgenic mouse reporter assays revealed that the in vivo activity pattern of the enhancer is conserved across a wide range of vertebrates, including fish, but not in snakes.
View Article and Find Full Text PDFWhole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of >35 epigenomic data sets from mouse and human pre- and postnatal hearts we created a comprehensive reference of >80,000 putative human heart enhancers.
View Article and Find Full Text PDFWe report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L.
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