1,123 research outputs found

    Cafeteria diet-induced obesity causes oxidative damage in white adipose

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    Obesity continues to be one of the most prominent public health dilemmas in the world. The complex interaction among the varied causes of obesity makes it a particularly challenging problem to address. While typical high-fat purified diets successfully induce weight gain in rodents, we have described a more robust model of diet-induced obesity based on feeding rats a diet consisting of highly palatable, energy-dense human junk foods – the “cafeteria” diet (CAF, 45-53% kcal from fat). We previously reported that CAF-fed rats became hyperphagic, gained more weight, and developed more severe hyperinsulinemia, hyperglycemia, and glucose intolerance compared to the lard-based 45% kcal from fat high fat diet–fed group. In addition, the CAF diet-fed group displayed a higher degree of inflammation in adipose and liver, mitochondrial dysfunction, and an increased concentration of lipid-derived, pro-inflammatory mediators. Building upon our previous findings, we aimed to determine mechanisms that underlie physiologic findings in the CAF diet. We investigated the effect of CAF diet-induced obesity on adipose tissue specifically using expression arrays and immunohistochemistry. Genomic evidence indicated the CAF diet induced alterations in the white adipose gene transcriptome, with notable suppression of glutathione-related genes and pathways involved in mitigating oxidative stress. Immunohistochemical analysis indicated a doubling in adipose lipid peroxidation marker 4-HNE levels compared to rats that remained lean on control standard chow diet. Our data indicates that the CAF diet drives an increase in oxidative damage in white adipose tissue that may affect tissue homeostasis. Oxidative stress drives activation of inflammatory kinases that can perturb insulin signaling leading to glucose intolerance and diabetes

    The differential importance of deep and shallow seagrass to Nekton assemblages of The Great Barrier Reef

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    Seagrass meadows are an important habitat for a variety of animals, including ecologically and socioeconomically important species. Seagrass meadows are recognised as providing species with nursery grounds, and as a migratory pathway to adjacent habitats. Despite their recognised importance, little is known about the species assemblages that occupy seagrass meadows of different depths in the coastal zone. Understanding differences in the distribution of species in seagrass at different depths, and differences in species diversity, abundance, biomass, and size spectra, is important to fully appreciate both the ecological significance and economic importance of these seagrass meadows. Here, we assess differences in the assemblage characteristics of fish, crustacea, and cephalopods (collectively, nekton) between deep ( > 9 m; Halophila spinulosa dominant) and shallow water ( < 2 m; Halodule uninervis and/or Zostera muelleri dominant) seagrass meadows of the central Great Barrier Reef coast of Queensland, Australia. Nekton assemblage structure differed between deep and shallow seagrass. Deeper meadows were typified by juvenile emperors (e.g., Lethrinus genivittatus), hairfinned leatherjacket (Paramonacanthus japonicus) and rabbitfish (e.g., Siganus fuscescens) in both biomass per unit effort (BPUE) and catch per unit effort (CPUE), whereas shallow meadows were typified by the green tiger prawn (Penaeus semisulcatus) and pugnose ponyfish (Secutor insidiator) in both BPUE and CPUE. Both meadow depths were distinct in their nekton assemblage, particularly for socioeconomically important species, with 11 species unique to both shallow and deep meadows. However, both meadow depths also included juveniles of socioeconomically important species found in adjacent habitats as adults. The total nekton CPUE was not different between deep and shallow seagrass, but the BPUE and body mass of individual animals were greater in deep than shallow seagrass. Size spectra analysis indicated that in both deep and shallow meadows, smaller animals predominated, even more so than theoretically expected for size spectra. Our findings highlight the unique attributes of both shallow and deeper water seagrass meadows, and identify the distinct and critically important role of deep seagrass meadows within the Great Barrier Reef World Heritage Area (GBRWHA) as a habitat for small and juvenile species, including those of local fisheries value

    The Lyman Alpha Reference Sample. VIII. Characterizing Lyman-Alpha Scattering in Nearby Galaxies

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    We examine the dust geometry and Ly{\alpha} scattering in the galaxies of the Lyman Alpha Reference Sample (LARS), a set of 14 nearby (0.02 < zz < 0.2) Ly{\alpha} emitting and starbursting systems with Hubble Space Telescope Ly{\alpha}, H{\alpha}, and H{\beta} imaging. We find that the global dust properties determined by line ratios are consistent with other studies, with some of the LARS galaxies exhibiting clumpy dust media while others of them show significantly lower Ly{\alpha} emission compared to their Balmer decrement. With the LARS imaging, we present Ly{\alpha}/H{\alpha} and H{\alpha}/H{\beta} maps with spatial resolutions as low as \sim 40 pc, and use these data to show that in most galaxies, the dust geometry is best modeled by three distinct regions: a central core where dust acts as a screen, an annulus where dust is distributed in clumps, and an outer envelope where Ly{\alpha} photons only scatter. We show that the dust that affects the escape of Ly{\alpha} is more restricted to the galaxies' central regions, while the larger Ly{\alpha} halos are generated by scattering at large radii. We present an empirical modeling technique to quantify how much Ly{\alpha} scatters in the halo, and find that this "characteristic" scattering distance correlates with the measured size of the Ly{\alpha} halo. We note that there exists a slight anti-correlation between the scattering distance of Ly{\alpha} and global dust properties.Comment: 32 pages, 51 figures, accepted to Ap

    Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2

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    Alzheimer\u27s disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. More than 200 pathogenic mutations have been identified in amyloid-β precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Additionally, common and rare variants occur within APP, PSEN1, and PSEN2 that may be risk factors, protective factors, or benign, non-pathogenic polymorphisms. Yet, to date, no single study has carefully examined the effect of all of the variants of unknown significance reported in APP, PSEN1 and PSEN2 on Aβ isoform levels in vitro. In this study, we analyzed Aβ isoform levels by ELISA in a cell-based system in which each reported pathogenic and risk variant in APP, PSEN1, and PSEN2 was expressed individually. In order to classify variants for which limited family history data is available, we have implemented an algorithm for determining pathogenicity using available information from multiple domains, including genetic, bioinformatic, and in vitro analyses. We identified 90 variants of unknown significance and classified 19 as likely pathogenic mutations. We also propose that five variants are possibly protective. In defining a subset of these variants as pathogenic, individuals from these families may eligible to enroll in observational studies and clinical trials

    UniCarb-DB: a database resource for glycomic discovery

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    Summary: Glycosylation is one of the most important post-translational modifications of proteins, known to be involved in pathogen recognition, innate immune response and protection of epithelial membranes. However, when compared to the tools and databases available for the processing of high-throughput proteomic data, the glycomic domain is severely lacking. While tools to assist the analysis of mass spectrometry (MS) and HPLC are continuously improving, there are few resources available to support liquid chromatography (LC)-MS/MS techniques for glycan structure profiling. Here, we present a platform for presenting oligosaccharide structures and fragment data characterized by LC-MS/MS strategies. The database is annotated with high-quality datasets and is designed to extend and reinforce those standards and ontologies developed by existing glycomics databases. Availability: http://www.unicarb-db.org Contact: [email protected]

    Leveraging eco-evolutionary models for gene drive risk assessment

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    Engineered gene drives create potential for both widespread benefits and irreversible harms to ecosystems. CRISPR-based systems of allelic conversion have rapidly accelerated gene drive research across diverse taxa, putting field trials and their necessary risk assessments on the horizon. Dynamic processbased models provide flexible quantitative platforms to predict gene drive outcomes in the context of system-specific ecological and evolutionary features. Here, we synthesize gene drive dynamic modeling studies to highlight research trends, knowledge gaps, and emergent principles, organized around their genetic, demographic, spatial, environmental, and implementation features. We identify the phenomena that most significantly influence model predictions, discuss limitations of biological complexity and uncertainty, and provide insights to promote responsible development and model-assisted risk assessment of gene drives. Supplemental files attached belo
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