43 research outputs found

    THE SOCIAL VALUE OF PUBLIC INVESTMENT IN CANADIAN WHEAT BREEDING RESEARCH

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    The level and distribution of the social benefits from public investment in Canadian wheat breeding research and extension activities are examined for the period 1946 to 1979. In addition, average and marginal rates of return are calculated. The results reveal that society has benefited substantially from such public investments, with producers receiving the greatest share of the benefits.Crop Production/Industries, Research and Development/Tech Change/Emerging Technologies,

    Prairie Crop Diversification

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    The Canadian prairies traditionally have been dominated by spring wheat production. Crop diversification is now being advocated to enhance farm-level risk management, ecological benefits, nutrient cycling, and pest and disease control, and to reduce the farm economy’s reliance on income from a single crop. There has always been interest in diversifying away from wheat, but until recently, economically feasible alternatives have been limited, and government policies may have constrained the shift to other crops. Knowing the impact of prices and policies on crop diversification is essential to understanding producer response and to determining strategies to enhance cropping diversity.Marketing,

    Simple and efficient profiling of transcription initiation and transcript levels with STRIPE-seq

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    Accurate mapping of transcription start sites (TSSs) is key for understanding transcriptional regulation. However, current protocols for genome-wide TSS profiling are laborious and/or expensive. We present Survey of TRanscription Initiation at Promoter Elements with high-throughput sequencing (STRIPE-seq), a simple, rapid, and cost-effective protocol for sequencing capped RNA 5' ends from as little as 50 ng total RNA. Including depletion of uncapped RNA and reaction cleanups, a STRIPE-seq library can be constructed in about 5 h. We show application of STRIPE-seq to TSS profiling in yeast and human cells and show that it can also be effectively used for quantification of transcript levels and analysis of differential gene expression. In conjunction with our ready-to-use computational workflows, STRIPE-seq is a straightforward, efficient means by which to probe the landscape of transcriptional initiation

    Flexible analysis of TSS mapping data and detection of TSS shifts with TSRexploreR

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    Heterogeneity in transcription initiation has important consequences for transcript stability and translation, and shifts in transcription start site (TSS) usage are prevalent in various developmental, metabolic, and disease contexts. Accordingly, numerous methods for global TSS profiling have been developed, including most recently Survey of TRanscription Initiation at Promoter Elements with high-throughput sequencing (STRIPE-seq), a method to profile transcription start sites (TSSs) on a genome-wide scale with significant cost and time savings compared to previous methods. In anticipation of more widespread adoption of STRIPE-seq and related methods for construction of promoter atlases and studies of differential gene expression, we built TSRexploreR, an R package for end-to-end analysis of TSS mapping data. TSRexploreR provides functions for TSS and transcription start region (TSR) detection, normalization, correlation, visualization, and differential TSS/TSR analyses. TSRexploreR is highly interoperable, accepting the data structures of TSS and TSR sets generated by several existing tools for processing and alignment of TSS mapping data, such as CAGEr for Cap Analysis of Gene Expression (CAGE) data. Lastly, TSRexploreR implements a novel approach for the detection of shifts in TSS distribution

    Lysine-Specific Demethylase 1 Mediates AKT Activity and Promotes Epithelial-to-Mesenchymal Transition in PIK3CA-Mutant Colorectal Cancer

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    Activation of the epithelial-mesenchymal transition (EMT) program is a critical mechanism for initiating cancer progression and migration. Colorectal cancers (CRCs) contain many genetic and epigenetic alterations that can contribute to EMT. Mutations activating the PI3K/AKT signaling pathway are observed in >40% of patients with CRC contributing to increased invasion and metastasis. Little is known about how oncogenic signaling pathways such as PI3K/AKT synergize with chromatin modifiers to activate the EMT program. Lysine Specific Demethylase 1 (LSD1) is a chromatin-modifying enzyme that is overexpressed in colorectal cancer (CRC) and enhances cell migration. In this study we determine that LSD1 expression is significantly elevated in CRC patients with mutation of the catalytic subunit of PI3K, PIK3CA, compared to CRC patients with WT PIK3CA. LSD1 enhances activation of the AKT kinase in CRC cells through a non-catalytic mechanism, acting as a scaffolding protein for the transcription-repressing CoREST complex. Additionally, growth of PIK3CA mutant CRC cells is uniquely dependent on LSD1. Knockdown or CRISPR knockout of LSD1 blocks AKT-mediated stabilization of the EMT-promoting transcription factor Snail and effectively blocks AKT-mediated EMT and migration. Overall we uniquely demonstrate that LSD1 mediates AKT activation in response to growth factors and oxidative stress, and LSD1-regulated AKT activity promotes EMT-like characteristics in a subset of PIK3CA mutant cells. Implications Our data supports the hypothesis that inhibitors targeting the CoREST complex may be clinically effective in CRC patients harboring PIK3CA mutations

    Histone H3 globular domain acetylation identifies a new class of enhancers

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    Histone acetylation is generally associated with active chromatin, but most studies have focused on the acetylation of histone tails. Various histone H3 and H4 tail acetylations mark the promoters of active genes. These modifications include acetylation of histone H3 at lysine 27 (H3K27ac), which blocks Polycomb-mediated trimethylation of H3K27 (H3K27me3). H3K27ac is also widely used to identify active enhancers, and the assumption has been that profiling H3K27ac is a comprehensive way of cataloguing the set of active enhancers in mammalian cell types. Here we show that acetylation of lysine residues in the globular domain of histone H3 (lysine 64 (H3K64ac) and lysine 122 (H3K122ac)) marks active gene promoters and also a subset of active enhancers. Moreover, we find a new class of active functional enhancers that is marked by H3K122ac but lacks H3K27ac. This work suggests that, to identify enhancers, a more comprehensive analysis of histone acetylation is required than has previously been considered

    LSST Science Book, Version 2.0

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    A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

    Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome.

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    The Polycomb repressive complexes PRC1 and PRC2 maintain embryonic stem cell (ESC) pluripotency by silencing lineage-specifying developmental regulator genes. Emerging evidence suggests that Polycomb complexes act through controlling spatial genome organization. We show that PRC1 functions as a master regulator of mouse ESC genome architecture by organizing genes in three-dimensional interaction networks. The strongest spatial network is composed of the four Hox gene clusters and early developmental transcription factor genes, the majority of which contact poised enhancers. Removal of Polycomb repression leads to disruption of promoter-promoter contacts in the Hox gene network. In contrast, promoter-enhancer contacts are maintained in the absence of Polycomb repression, with accompanying widespread acquisition of active chromatin signatures at network enhancers and pronounced transcriptional upregulation of network genes. Thus, PRC1 physically constrains developmental transcription factor genes and their enhancers in a silenced but poised spatial network. We propose that the selective release of genes from this spatial network underlies cell fate specification during early embryonic development
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