244 research outputs found

    Horizontal gene transfer-mediated bacterial strain variation affects host fitness in Drosophila

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    How microbes affect host fitness and environmental adaptation has become a fundamental research question in evolutionary biology. To better understand the role of microbial genomic variation for host fitness, we tested for associations of bacterial genomic variation and Drosophila melanogaster offspring number in a microbial Genome Wide Association Study (GWAS)

    Sex dimorphism and sepsis: a novel approach

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    Common structuring principles of the Drosophila melanogaster microbiome on a continental scale and between host and substrate

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    Summary The relative importance of host control, environmental effects and stochasticity in the assemblage of host-associated microbiomes is being debated. We analysed the microbiome among fly populations that were sampled across Europe by the European Drosophila Population Genomics Consortium (DrosEU). In order to better understand the structuring principles of the natural D. melanogaster microbiome, we combined environmental data on climate and food-substrate with dense genomic data on host populations and microbiome profiling. Food-substrate, temperature, and host population structure correlated with microbiome structure. Microbes, whose abundance was co-structured with host populations, also differed in abundance between flies and their substrate in an independent survey. This finding suggests common, host-related structuring principles of the microbiome on different spatial scales

    Characterizing the secretome of licensed hiPSC-derived MSCs

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    Although mesenchymal stromal cells (MSCs) from primary tissues have been successfully applied in the clinic, their expansion capabilities are limited and results are variable. MSCs derived from human-induced pluripotent stem cells (hiMSCs) are expected to overcome these limitations and serve as a reproducible and sustainable cell source. We have explored characteristics and therapeutic potential of hiMSCs in comparison to hBMSCs. RNA sequencing confirmed high resemblance, with average Pearson correlation of 0.88 and Jaccard similarity index of 0.99, and similar to hBMSCs the hiMSCs released extracellular vesicles with in vitro immunomodulatory properties. Potency assay with TNF alpha and IFN gamma demonstrated an increase in well-known immunomodulatory genes such as IDO1, CXCL8/IL8, and HLA-DRA which was also highlighted by enhanced secretion in the media. Notably, expression of 125 genes increased more than 1000-fold. These genes were predicted to be regulated by NFKB signaling, known to play a central role in immune response. Altogether, our data qualify hiMSCs as a promising source for cell therapy and/or cell-based therapeutic products. Additionally, the herewith generated database will add to our understanding of the mode of action of regenerative cell-based therapies and could be used to identify relevant potency markers.Molecular Epidemiolog

    Chances and Limitations of Wild Bird Monitoring for the Avian Influenza Virus H5N1 — Detection of Pathogens Highly Mobile in Time and Space

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    Highly pathogenic influenza virus (HPAIV) H5N1 proved to be remarkably mobile in migratory bird populations where it has led to extensive outbreaks for which the true number of affected birds usually cannot be determined. For the evaluation of avian influenza monitoring and HPAIV early warning systems, we propose a time-series analysis that includes the estimation of confidence intervals for (i) the prevalence in outbreak situations or (ii) in the apparent absence of disease in time intervals for specified regional units. For the German outbreak regions in 2006 and 2007, the upper 95% confidence limit allowed the detection of prevalences below 1% only for certain time intervals. Although more than 25,000 birds were sampled in Germany per year, the upper 95% confidence limit did not fall below 5% in the outbreak regions for most of the time. The proposed analysis can be used to monitor water bodies and high risk areas, also as part of an early-warning system. Chances for an improved targeting of the monitoring system as part of a risk-based approach are discussed with the perspective of reducing sample sizes

    Cometary Origin of the Zodiacal Cloud and Carbonaceous Micrometeorites

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    The zodiacal cloud is a thick circumsolar disk of small debris particles produced by asteroid collisions and comets. Here, we present a zodiacal cloud model based on the orbital properties and lifetimes of comets and asteroids, and on the dynamical evolution of dust after ejection. The model is quantitatively constrained by IRAS observations of thermal emission, but also qualitatively consistent with other zodiacal cloud observations. We find that 85-95% of the observed mid-infrared emission is produced by particles from the Jupiter-family comets (JFCs) and <<10% by dust from long period comets. Asteroidal dust is found to be present at <<10%. We suggest that spontaneous disruptions of JFCs, rather than the usual cometary activity driven by sublimating volatiles, is the main mechanism that librates cometary particles into the zodiacal cloud. Our results imply that JFC particles represent \sim85% of the total mass influx at Earth. Since their atmospheric entry speeds are typically low (\approx14.5 km s1^{-1} mean for D=100-200 μ\mum with \approx12 km s1^{-1} being the most common case), many JFC grains should survive frictional heating and land on the Earth's surface. This explains why most micrometeorites collected in antarctic ice have primitive carbonaceous composition. The present mass of the inner zodiacal cloud at <<5 AU is estimated to be 1-2×10192\times10^{19} g, mainly in D=100-200 μ\mum particles. The inner zodiacal cloud should have been >104>10^4 times brighter during the Late Heavy Bombardment (LHB) epoch \approx3.8 Gyr ago, when the outer planets scattered numerous comets into the inner solar system. The bright debris disks with a large 24-μ\mum excess observed around mature stars may be an indication of massive cometary populations existing in those systems

    Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo

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    Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C–Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living culture
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