665 research outputs found

    A Western-style obesogenic diet alters maternal metabolic physiology with consequences for fetal nutrient acquisition in mice

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    In the Western world, obesogenic diets containing high fat and high sugar (HFHS) are commonly consumed during pregnancy. However, the impacts of a HFHS diet during pregnancy on maternal insulin sensitivity and signalling in relation to feto-placental growth and glucose utilization are unknown. The present study examined the effects of a HFHS diet during mouse pregnancy on maternal glucose tolerance and insulin resistance, as well as, on feto-placental glucose metabolism. Female mice were fed a control or HFHS diet from day (D) 1 of pregnancy (term = D20.5). At D16 or D19, dams were assessed for body composition, metabolite and hormone concentrations, tissue abundance of growth and metabolic signalling pathways, glucose tolerance and utilization and insulin sensitivity. HFHS feeding perturbed maternal insulin sensitivity in late pregnancy; hepatic insulin sensitivity was higher, whereas sensitivity of the skeletal muscle and white adipose tissue was lower in HFHS than control dams. These changes were accompanied by increased adiposity and reduced glucose production and glucose tolerance of HFHS dams. The HFHS diet also disturbed the hormone and metabolite milieu and altered expression of growth and metabolic signalling pathways in maternal tissues. Furthermore, HFHS feeding was associated with impaired feto-placental glucose metabolism and growth. A HFHS diet during pregnancy therefore causes maternal metabolic dysfunction with consequences for maternal nutrient allocation for fetal growth. These findings have implications for the health of women and their infants, who consume HFHS diets during pregnancy.We are grateful to the Medical Research Council (MRC) for funding the research through a studentship to BM (MR/J500458/1), an in vivo skills award (MRC CORD G0600717) and the MRC Metabolic Diseases Unit (MC_UU_12012/4)

    A Rapid and Economic In-House DNA Purification Method Using Glass Syringe Filters

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    Background Purity, yield, speed and cost are important considerations in plasmid purification, but it is difficult to achieve all of these at the same time. Currently, there are many protocols and kits for DNA purification, however none maximize all four considerations. Methodology/Principal Findings We now describe a fast, efficient and economic in-house protocol for plasmid preparation using glass syringe filters. Plasmid yield and quality as determined by enzyme digestion and transfection efficiency were equivalent to the expensive commercial kits. Importantly, the time required for purification was much less than that required using a commercial kit. Conclusions/Significance This method provides DNA yield and quality similar to that obtained with commercial kits, but is more rapid and less costly.This research was supported by Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

    Prediction of 7-year psychopathology from mother-infant joint attention behaviours: a nested case–control study

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    <br>Background: To investigate whether later diagnosis of psychiatric disorder can be predicted from analysis of mother-infant joint attention (JA) behaviours in social-communicative interaction at 12 months.</br> <br>Method: Using data from a large contemporary birth cohort, we examined 159 videos of a mother-infant interaction for joint attention behaviour when children were aged one year, sampled from within the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Fifty-three of the videos involved infants who were later considered to have a psychiatric disorder at seven years and 106 were same aged controls. Psychopathologies included in the case group were disruptive behaviour disorders, oppositional-conduct disorder, attention-deficit/hyperactivity disorder, pervasive development disorder, anxiety and depressive disorders. Psychiatric diagnoses were obtained using the Development and Wellbeing Assessment when the children were seven years old.</br> <br>Results: None of the three JA behaviours (shared look rate, shared attention rate and shared attention intensity) showed a significant association with the primary outcome of case–control status. Only shared look rate predicted any of the exploratory sub-diagnosis outcomes and was found to be positively associated with later oppositional-conduct disorders (OR [95% CI]: 1.5 [1.0, 2.3]; p = 0.041).</br><br>Conclusions: JA behaviours did not, in general, predict later psychopathology. However, shared look was positively associated with later oppositional-conduct disorders. This suggests that some features of JA may be early markers of later psychopathology. Further investigation will be required to determine whether any JA behaviours can be used to screen for families in need of intervention.</br&gt

    Histological changes in intra-oral skin flaps

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    This review outlines the histological features of intra-oral skin flaps and their pathology as encountered in a routine head and neck diagnostic histopathology service. Problems in recognising and interpreting unfamiliar and complex appearances, and areas of diagnostic and prognostic uncertainty, are highlighted

    Marine Macroalgal Diversity Assessment of Saba Bank, Netherlands Antilles

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    Background: Located in the Dutch Windward Islands, Saba Bank is a flat-topped seamount (20–45 m deep in the shallower regions). The primary goals of the survey were to improve knowledge of biodiversity for one of the world’s most significant, but little-known, seamounts and to increase basic data and analyses to promote the development of an improved management plan. Methodology/Principal Findings: Our team of three divers used scuba to collect algal samples to depths of 50 m at 17 dive sites. Over 360 macrophyte specimens (12 putative new species) were collected, more than 1,000 photographs were taken in truly exceptional habitats, and three astonishing new seaweed community types were discovered. These included: (1) β€˜β€˜Field of Greens’ ’ (N 17u30.6209, W63u27.7079) dominated by green seaweeds as well as some filamentous reds, (2) β€˜β€˜Brown Town’ ’ (N 17u28.0279, W63u14.9449) dominated by large brown algae, and (3) β€˜β€˜Seaweed City’ ’ (N 17u26.4859, W63u16.8509) with a diversity of spectacular fleshy red algae. Conclusions/Significance: Dives to 30 m in the more two-dimensional interior habitats revealed particularly robust specimens of algae typical of shallower seagrass beds, but here in the total absence of any seagrasses (seagrasses generally do not grow below 20 m). Our preliminary estimate of the number of total seaweed species on Saba Bank ranges from a minimum of 150 to 200. Few filamentous and thin sheet forms indicative of stressed or physically disturbed environments were observed. A more precise number still awaits further microscopic and molecular examinations in the laboratory. The expedition, while intensive, has only scratched the surface of this unique submerged seamount/atoll

    The SAMI Galaxy Survey: The role of disc fading and progenitor bias in kinematic transitions

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    We use comparisons between the Sydney-AAO Multi-object Integral Field Spectrograph (SAMI) Galaxy Survey and equilibrium galaxy models to infer the importance of disc fading in the transition of spirals into lenticular (S0) galaxies. The local S0 population has both higher photometric concentration and lower stellar spin than spiral galaxies of comparable mass and we test whether this separation can be accounted for by passive aging alone. We construct a suite of dynamically self-consistent galaxy models, with a bulge, disc, and halo using the galactics code. The dispersion-dominated bulge is given a uniformly old stellar population, while the disc is given a current star formation rate putting it on the main sequence, followed by sudden instantaneous quenching. We then generate mock observables (r-band images, stellar velocity, and dispersion maps) as a function of time since quenching for a range of bulge/total (B/T) mass ratios. The disc fading leads to a decline in measured spin as the bulge contribution becomes more dominant, and also leads to increased concentration. However, the quantitative changes observed after 5 Gyr of disc fading cannot account for all of the observed difference. We see similar results if we instead subdivide our SAMI Galaxy Survey sample by star formation (relative to the main sequence). We use EAGLE simulations to also take into account progenitor bias, using size evolution to infer quenching time. The EAGLE simulations suggest that the progenitors of current passive galaxies typically have slightly higher spin than present day star-forming disc galaxies of the same mass. As a result, progenitor bias moves the data further from the disc fading model scenario, implying that intrinsic dynamical evolution must be important in the transition from star-forming discs to passive discs

    A Meta-Analysis of the Existing Knowledge of Immunoreactivity against Hepatitis C Virus (HCV)

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    Approximately 3% of the world population is infected by HCV, which represents a major global health challenge. Almost 400 different scientific reports present immunological data related to T cell and antibody epitopes derived from HCV literature. Analysis of all HCV-related epitope hosted in the Immune Epitope Database (IEDB), a repository of freely accessible immune epitope data, revealed more than 1500 and 1900 distinct T cell and antibody epitopes, respectively. The inventory of all data revealed specific trends in terms of the host and the HCV genotypes from which sequences were derived. Upon further analysis we found that this large number of epitopes reflects overlapping structures, and homologous sequences derived from different HCV isolates. To access and visualize this information we developed a novel strategy that assembles large sets of epitope data, maps them onto reference genomes and displays the frequency of positive responses. Compilation of the HCV immune reactivity from hundreds of different studies, revealed a complex and thorough picture of HCV immune epitope data to date. The results pinpoint areas of more intense reactivity or research activities at the level of antibody, CD4 and CD8 responses for each of the individual HCV proteins. In general, the areas targeted by the different effector immune functions were distinct and antibody reactivity was positively correlated with hydrophilicity, while T cell reactivity correlated with hydrophobicity. At the sequence level, epitopes frequently recognized by both T cell and B cell correlated with low variability, and our analysis thus highlighted areas of potential interest for practical applications. The human reactivity was further analyzed to pinpoint differential patterns of reactivity associated with acute versus chronic infection, to reveal the apparent impact of glycosylation on T cell, but not antibody responses, and to highlight a paucity of studies involved antibody epitopes associated with virus neutralization

    Highly Parallel Translation of DNA Sequences into Small Molecules

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    A large body of in vitro evolution work establishes the utility of biopolymer libraries comprising 1010 to 1015 distinct molecules for the discovery of nanomolar-affinity ligands to proteins.[1], [2], [3], [4], [5] Small-molecule libraries of comparable complexity will likely provide nanomolar-affinity small-molecule ligands.[6], [7] Unlike biopolymers, small molecules can offer the advantages of cell permeability, low immunogenicity, metabolic stability, rapid diffusion and inexpensive mass production. It is thought that such desirable in vivo behavior is correlated with the physical properties of small molecules, specifically a limited number of hydrogen bond donors and acceptors, a defined range of hydrophobicity, and most importantly, molecular weights less than 500 Daltons.[8] Creating a collection of 1010 to 1015 small molecules that meet these criteria requires the use of hundreds to thousands of diversity elements per step in a combinatorial synthesis of three to five steps. With this goal in mind, we have reported a set of mesofluidic devices that enable DNA-programmed combinatorial chemistry in a highly parallel 384-well plate format. Here, we demonstrate that these devices can translate DNA genes encoding 384 diversity elements per coding position into corresponding small-molecule gene products. This robust and efficient procedure yields small molecule-DNA conjugates suitable for in vitro evolution experiments
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