6 research outputs found

    Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans

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    Background: Long non-coding RNAs (lncRNAs) are increasingly implicated as gene regulators and may ultimately be more numerous than protein-coding genes in the human genome. Despite large numbers of reported lncRNAs, reference annotations are likely incomplete due to their lower and tighter tissue-specific expression compared to mRNAs. An unexplored factor potentially confounding lncRNA identification is inter-individual expression variability. Here, we characterize lncRNA natural expression variability in human primary granulocytes. Results: We annotate granulocyte lncRNAs and mRNAs in RNA-seq data from 10 healthy individuals, identifying multiple lncRNAs absent from reference annotations, and use this to investigate three known features (higher tissue-specificity, lower expression, and reduced splicing efficiency) of lncRNAs relative to mRNAs. Expression variability was examined in seven individuals sampled three times at 1- or more than 1-month intervals. We show that lncRNAs display significantly more inter-individual expression variability compared to mRNAs. We confirm this finding in two independent human datasets by analyzing multiple tissues from the GTEx project and lymphoblastoid cell lines from the GEUVADIS project. Using the latter dataset we also show that including more human donors into the transcriptome annotation pipeline allows identification of an increasing number of lncRNAs, but minimally affects mRNA gene number. Conclusions: A comprehensive annotation of lncRNAs is known to require an approach that is sensitive to low and tight tissue-specific expression. Here we show that increased inter-individual expression variability is an additional general lncRNA feature to consider when creating a comprehensive annotation of human lncRNAs or proposing their use as prognostic or disease markers

    Influence of CaO on structure and permeability of clayey soil

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    The aim of this study was to determine the effect of quicklime (1 - 8% CaO) and maturation time (1 - 540 days) on the structure of clayey soil compacted at optimum moisture content by Proctor standard energy and whether expected change in structure affects the long - term permeability. The change of pore space of compacted loess with 1-8% lime (CaO) was studied by mercury porosimetry (MIP) for a long period of maturation (from 1 to 540 days). Development of pozzolanic reactions were monitored by measuring the pH. The development of new mineral phases (calcium silicate hydrates, calcium aluminate hydrates and calcium aluminate carbonate hydrate) in the treated soil was investigated by using X-Ray diffraction. The MIP indicated that 2% of CaO were sufficient for long term pozzolanic reaction. The threshold value is below the initial consumption of lime determined from the pH measurements (Eades and Grim, 1966). The alteration of the voids of the lime treated soil is noticeable, but the pH value can not drop below 11.7. At 4% of CaO, at 8% of CaO respectively, the macroporosity kept decreasing due to increasing mesoporosity for 360 curing days, for 540 curing days respectively, due to the new mineral phases. At 2% of CaO, the decrease of the macroporosity stops after 120 days. Below 2% of lime, the..

    Additional file 7: of Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans

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    A List of robust lncRNA transcripts in granulocytes (2,825 transcripts): columns are formatted as a BED12 file. B List of robust well expressed (RPKM >1) lncRNA transcripts in granulocytes (931 transcripts): columns are formatted as a BED12 file. (XLSX 250 kb

    npj Systems Biology and Applications volume / A time-resolved molecular map of the macrophage response to VSV infection

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    Studying the relationship between virus infection and cellular response is paradigmatic for our understanding of how perturbation changes biological systems. Immune response, in this context is a complex yet evolutionarily adapted and robust cellular change, and is experimentally amenable to molecular analysis. To visualize the full cellular response to virus infection, we performed temporal transcriptomics, proteomics, and phosphoproteomics analysis of vesicular stomatitis virus (VSV)-infected mouse macrophages. This enabled the understanding of how infection-induced changes in host gene and protein expression are coordinated with post-translational modifications by cells in time to best measure and control the infection process. The vast and complex molecular changes measured could be decomposed in a limited number of clusters within each category (transcripts, proteins, and protein phosphorylation) each with own kinetic parameter and characteristic pathways/processes, suggesting multiple regulatory options in the overall sensing and homeostatic program. Altogether, the data underscored a prevalent executive function to phosphorylation. Resolution of the molecular events affecting the RIG-I pathway, central to viral recognition, reveals that phosphorylation of the key innate immunity adaptor mitochondrial antiviral-signaling protein (MAVS) on S328/S330 is necessary for activation of type-I interferon and nuclear factor B (NFB) pathways. To further understand the hierarchical relationships, we analyzed kinasesubstrate relationships and found RAF1 and, to a lesser extent, ARAF to be inhibiting VSV replication and necessary for NFB activation, and AKT2, but not AKT1, to be supporting VSV replication. Integrated analysis using the omics data revealed co-regulation of transmembrane transporters including SLC7A11, which was subsequently validated as a host factor in the VSV replication. The data sets are predicted to greatly empower future studies on the functional organization of the response of macrophages to viral challenges.(VLID)460623

    A weighty problem: metabolic perturbations and the obesity-cancer link

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