Cytosine Methylation Dysregulation in Neonates Following Intrauterine Growth Restriction

Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM), manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR) and control subjects.Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4alpha (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins.Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease

Tethered capsule endomicroscopy enables less-invasive imaging of gastrointestinal tract microstructure

Here, we introduce “tethered capsule endomicroscopy,” that involves swallowing an optomechanically-engineered pill that captures cross-sectional, 30 μm (lateral) × 7 μm (axial) resolution, microscopic images of the gut wall as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases

Automated segmentation and quantification of airway mucus with endobronchial optical coherence tomography

We propose a novel suite of algorithms for automatically segmenting the airway lumen and mucus in endobronchial optical coherence tomography (OCT) data sets, as well as a novel approach for quantifying the contents of the mucus. Mucus and lumen were segmented using a robust, multi-stage algorithm that requires only minimal input regarding sheath geometry. The algorithm performance was highly accurate in a wide range of airway and noise conditions. Mucus was classified using mean backscattering intensity and grey level co-occurrence matrix (GLCM) statistics. We evaluated our techniques in vivo in asthmatic and non-asthmatic volunteers

Optimizing flushing parameters in intracoronary optical coherence tomography: an in vivo swine study

Intracoronary optical frequency domain imaging (OFDI), requires the displacement of blood for clear visualization of the artery wall. Radiographic contrast agents are highly effective at displacing blood however, may increase the risk of contrast-induced nephropathy. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. The aim of this work was to determine the optimal flushing parameters necessary to reliably perform intracoronary OFDI while reducing the volume of administered radiographic contrast, and assess the influence of flushing media choice on vessel wall measurements. 144 OFDI pullbacks were acquired together with synchronized EKG and intracoronary pressure wire recordings in three swine. OFDI images were graded on diagnostic quality and quantitative comparisons of flushing efficiency and intracoronary cross-sectional area with and without precise refractive index calibration were performed. Flushing media with higher viscosities resulted in rapid and efficient blood displacement. Media with lower viscosities resulted in increased blood-media transition zones, reducing the pullback length of diagnostic quality images obtained. Flushing efficiency was found to increase with increases in flow rate and duration. Calculations of lumen area using different flushing media were significantly different, varying up to 23 % (p < 0.0001). This error was eliminated with careful refractive index calibration. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. For patients with sensitivity to contrast, to reduce the risk of contrast induced nephrotoxicity we recommend that intracoronary OFDI be conducted with flushing solutions containing little or no radiographic contrast. In addition, our findings show that careful refractive index compensation should be performed, taking into account the specific contrast agent used, in order to obtain accurate intravascular OFDI measurements.Merck & Co., Inc.National Institutes of Health (U.S.) (Grant Numbers R00CA134920, R01HL076398, R01HL093717

Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells and airway structural cells to type 2 inflammation

Despite systemic sensitization, not all allergic individuals develop asthma symptoms upon airborne allergen exposure. Determination of the factors that lead to the asthma phenotype in allergic individuals could guide treatment and identify novel therapeutic targets. In this study, we utilized segmental allergen challenge (SAC) of allergic asthmatics (AA) and allergic non-asthmatic controls (AC) to determine if there are differences in the airway immune response or airway structural cells that could drive the development of asthma. Both groups developed prominent allergic airway inflammation in response to allergen. However, asthmatic subjects had markedly higher levels of innate type 2 receptors on allergen-specific CD4+ T cells recruited into the airway. There were also increased levels of type 2 cytokines, increased total mucin and increased MUC5AC in response to allergen in the airways of AA subjects. Furthermore, type 2 cytokine levels correlated with the mucin response in AA but not AC subjects, suggesting differences in the airway epithelial response to inflammation. Finally, AA subjects had increased airway smooth muscle mass at baseline measured in vivo using novel orientation-registered optical coherence tomography (OR-OCT). Our data demonstrate that the development of allergic asthma is dependent on the responsiveness of allergen-specific CD4+ T cells to innate type 2 mediators as well as increased sensitivity of airway epithelial cells and smooth muscle to type 2 inflammation

An expert-driven framework for applying eDNA tools to improve biosecurity in the Antarctic

Signatories to the Antarctic Treaty System’s Environmental Protocol are committed to preventing incursions of non-native species into Antarctica, but systematic surveillance is rare. Environmental DNA (eDNA) methods provide new opportunities for enhancing detection of non-native species and biosecurity monitoring. To be effective for Antarctic biosecurity, eDNA tests must have appropriate sensitivity and specificity to distinguish non-native from native Antarctic species, and be fit-for-purpose. This requires knowledge of the priority risk species or taxonomic groups for which eDNA surveillance will be informative, validated eDNA assays for those species or groups, and reference DNA sequences for both target non-native and related native Antarctic species. Here, we used an expert elicitation process and decision-by-consensus approach to identify and assess priority biosecurity risks for the Australian Antarctic Program (AAP) in East Antarctica, including identifying high priority non-native species and their potential transport pathways. We determined that the priority targets for biosecurity monitoring were not individual species, but rather broader taxonomic groups such as mussels (Mytilus species), tunicates (Ascidiacea), springtails (Collembola), and grasses (Poaceae). These groups each include multiple species with high risks of introduction to and/or establishment in Antarctica. The most appropriate eDNA methods for the AAP must be capable of detecting a range of species within these high-risk groups (e.g., eDNA metabarcoding). We conclude that the most beneficial Antarctic eDNA biosecurity applications include surveillance of marine species in nearshore environments, terrestrial invertebrates, and biofouling species on vessels visiting Antarctica. An urgent need exists to identify suitable genetic markers for detecting priority species groups, establish baseline terrestrial and marine biodiversity for Antarctic stations, and develop eDNA sampling methods for detecting biofouling organisms

An expert-driven framework for applying eDNA tools to improve biosecurity in the Antarctic

Signatories to the Antarctic Treaty System’s Environmental Protocol are committed to preventing incursions of non-native species into Antarctica, but systematic surveillance is rare. Environmental DNA (eDNA) methods provide new opportunities for enhancing detection of non-native species and biosecurity monitoring. To be effective for Antarctic biosecurity, eDNA tests must have appropriate sensitivity and specificity to distinguish non-native from native Antarctic species, and be fit-for-purpose. This requires knowledge of the priority risk species or taxonomic groups for which eDNA surveillance will be informative, validated eDNA assays for those species or groups, and reference DNA sequences for both target non-native and related native Antarctic species. Here, we used an expert elicitation process and decision-by-consensus approach to identify and assess priority biosecurity risks for the Australian Antarctic Program (AAP) in East Antarctica, including identifying high priority non-native species and their potential transport pathways. We determined that the priority targets for biosecurity monitoring were not individual species, but rather broader taxonomic groups such as mussels (Mytilus species), tunicates (Ascidiacea), springtails (Collembola), and grasses (Poaceae). These groups each include multiple species with high risks of introduction to and/or establishment in Antarctica. The most appropriate eDNA methods for the AAP must be capable of detecting a range of species within these high-risk groups (e.g., eDNA metabarcoding). We conclude that the most beneficial Antarctic eDNA biosecurity applications include surveillance of marine species in nearshore environments, terrestrial invertebrates, and biofouling species on vessels visiting Antarctica. An urgent need exists to identify suitable genetic markers for detecting priority species groups, establish baseline terrestrial and marine biodiversity for Antarctic stations, and develop eDNA sampling methods for detecting biofouling organisms.This work was supported as a Science Innovation Project by the Department of Agriculture, Water and the Environment’s Science Innovation Program funding 2021–22 (project team: A.J.M., L.J.C., D.M.B., C.K.K., J.S.S. and L.S.). Support was also provided (to J.D.S, E.L.J., S.A.R., J.S.S., M.I.S., J.M.S., N.G.W.) from Australian Research Council SRIEAS grant SR200100005. P.C. and K.A.H. are supported by NERC core funding to the BAS Biodiversity, Evolution and Adaptation Team and Environment Office, respectively. L.R.P. and M.G. are supported by Biodiversa ASICS funding

An expert-driven framework for applying eDNA tools to improve biosecurity in the Antarctic

SUPPLEMENTARY MATERIAL : FIGURE S1. Map of Antarctica and the Southern Ocean including year-round Australian stations. Sourced from the Australian Antarctic Data Centre (https://data.aad.gov.au/map-catalogue/map/14159) under a Creative Commons Attribution 4.0 Unported License. TABLE S1. Ranked list of marine species that represent the greatest perceived risk of arrival, establishment, and impact via the Australian Antarctic Program. TABLE S2. Ranked list of terrestrial invertebrate species that represent the greatest perceived risk of arrival, establishment, and impact via the Australian Antarctic Program. TABLE S3. Ranked list of terrestrial plant species that represent the greatest perceived risk of arrival, establishment, and impact via the Australian Antarctic Program. TABLE S4. Genetic resources currently available for priority species, including species-specific real-time PCR assays, and reference sequences for DNA barcoding genes or mitochondrial/chloroplast genomes.Signatories to the Antarctic Treaty System’s Environmental Protocol are committed to preventing incursions of non-native species into Antarctica, but systematic surveillance is rare. Environmental DNA (eDNA) methods provide new opportunities for enhancing detection of non-native species and biosecurity monitoring. To be effective for Antarctic biosecurity, eDNA tests must have appropriate sensitivity and specificity to distinguish non-native from native Antarctic species, and be fit-for-purpose. This requires knowledge of the priority risk species or taxonomic groups for which eDNA surveillance will be informative, validated eDNA assays for those species or groups, and reference DNA sequences for both target non-native and related native Antarctic species. Here, we used an expert elicitation process and decision-by- consensus approach to identify and assess priority biosecurity risks for the Australian Antarctic Program (AAP) in East Antarctica, including identifying high priority non-native species and their potential transport pathways. We determined that the priority targets for biosecurity monitoring were not individual species, but rather broader taxonomic groups such as mussels (Mytilus species), tunicates (Ascidiacea), springtails (Collembola), and grasses (Poaceae). These groups each include multiple species with high risks of introduction to and/or establishment in Antarctica. The most appropriate eDNA methods for the AAP must be capable of detecting a range of species within these high-risk groups (e.g., eDNA metabarcoding). We conclude that the most beneficial Antarctic eDNA biosecurity applications include surveillance of marine species in nearshore environments, terrestrial invertebrates, and biofouling species on vessels visiting Antarctica. An urgent need exists to identify suitable genetic markers for detecting priority species groups, establish baseline terrestrial and marine biodiversity for Antarctic stations, and develop eDNA sampling methods for detecting biofouling organisms.A Science Innovation Project by the Department of Agriculture, Water and the Environment’s Science Innovation Program; Australian Research Council; NERC core funding to the BAS Biodiversity, Evolution and Adaptation Team and Environment Office; and Biodiversa ASICS funding.http://www.reabic.net/journals/mbi/Default.aspxhj2024Plant Production and Soil ScienceSDG-14:Life below wate

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Heart wall velocimetry and exogenous contrast-based cardiac flow imaging in Drosophila melanogaster using Doppler optical coherence tomography

Drosophila melanogaster (fruit fly) is a central organism in biology and is becoming increasingly important in the cardiovascular sciences. Prior work in optical imaging of the D. melanogaster heart has focused on static and dynamic structural anatomy. In the study, it is demonstrated that Doppler optical coherence tomography can quantify dynamic heart wall velocity and hemolymph flow in adult D. melanogaster. Since hemolymph is optically transparent, a novel exogenous contrast technique is demonstrated to increase the backscatter-based intracardiac Doppler flow signal. The results presented here open up new possibilities for functional cardiovascular phenotyping of normal and mutant D. melanogaster.Frederick H. Lovejoy FundChildren's Hospital (Boston, Mass.)AMA FoundationAMA Foundation (Seed Grant)National Institutes of Health (U.S.) (NIH R01HL076398)National Institutes of Health (U.S.) (NIH R01HL076398)United States. Air Force Office of Scientific Research (Medical Free Electron Laser Program FA9550-04-1-0079