Characterization of the selectivity of SMN splicing modifiers in SMA type I fibroblasts by RNASeq Overall design: In total 12 samples were analyzed, divided into four distinct groups (treated with SMN-C3 @ 500 nM; controls for SMN-C3; treated with SMN-C1 @ 100 nM; controls for SMN-C1) containing 3 replicates each.
Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy.
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View SamplesSmall molecule BET bromodomain inhibitors (BETi) are actively being pursued in clinical trials for the treatment of a variety of cancers, however, the mechanisms of resistance to targeted BET protein inhibitors remain poorly understood. Using a novel mass spectrometry approach that globally measures kinase signaling at the proteomic level, we evaluated the response of the kinome to targeted BET inhibitor treatment in a panel of BRD4-dependent ovarian carcinoma (OC) cell lines. Despite initial inhibitory effects of BETi, OC cells acquired resistance following sustained treatment with the BETi, JQ1. Through application of Multiplexed Inhibitor Beads (MIBs) and mass spectrometry, we demonstrate that BETi resistance is mediated by adaptive kinome reprogramming, where activation of compensatory pro-survival kinase networks overcomes BET protein inhibition. Furthermore, drug combinations blocking these kinases may prevent or delay the development of drug resistance and enhance the efficacy of BET inhibitor therapy. Overall design: RNAseq was employed to identify changes in kinase RNA expression following short term (48h) or chronic (JQ1R) JQ1 treatment in three different ovarian cancer cell lines.
Resistance to BET Bromodomain Inhibitors Is Mediated by Kinome Reprogramming in Ovarian Cancer.
Cell line, Subject
View SamplesFiltered selection coupled with support vector machines generate functionally relevant prediction model for colorectal cancer. In this study, we built a model that uses Support Vector Machine (SVM) to classify cancer and normal samples using Affymetrix exon microarray data obtained from 90 samples of 48 patients diagnosed with CRC. From the 22,011 genes, we selected the 20, 30, 50, 100, 200, 300 and 500 genes most relevant to CRC using the Minimum-RedundancyMaximum-Relevance (mRMR) technique. With these gene sets, an SVM model was designed using four different kernel types (linear, polynomial, radial basis function and sigmoid).
Filtered selection coupled with support vector machines generate a functionally relevant prediction model for colorectal cancer.
Sex, Age, Specimen part, Disease stage
View SamplesTo investigate the effects of quality of fat in a high fat diet (HFD) over time on hepatic lipid storage and transcriptome in mice.
Eicosapentaenoic and docosahexaenoic acid-enriched high fat diet delays the development of fatty liver in mice.
Sex, Specimen part, Time
View SamplesIdentifying molecular effects between herring and beef diet in Ldlr-/- mice
Identifying molecular effects of diet through systems biology: influence of herring diet on sterol metabolism and protein turnover in mice.
Specimen part
View SamplesThe nuclear exosome performs critical functions in non-coding RNA processing, and in diverse surveillance functions including the quality control of mRNP formation, and in the removal of pervasive transcripts. Most non-coding RNAs and pervasive nascent transcripts are targeted by the Nrd1p-Nab3p-Sen1p (NNS) complex to terminate Pol II transcription coupled to nuclear exosome degradation or 3´-end trimming. Prior to nuclear exosome activity, the Trf4p-Air2p-Mtr4p polyadenylation complex adds an oligo-A tail to exosome substrates. Inactivating exosome activity stabilizes and lengthens these A-tails. We utilized high-throughput 3´-end poly(A)+ sequencing to identify at nucleotide resolution the 3´ ends targeted by the nuclear exosome, and determine the sites of NNS-dependent termination genome-wide. Overall design: 3´-end mapping of wild-type and various nuclear exosome mutant strains, either using gene knockouts or the anchor away system to conditionally deplete FRB-tagged proteins from the nucleus
Common genomic elements promote transcriptional and DNA replication roadblocks.
Subject
View SamplesWe generated gene expression profiles of N2 (wild type) and strain FAS43 (Histone H3.3 null worms containing knockout alleles of all genes with homology to human histone H3.3: his-69, his-70, his-71, his-72, his-74) at embryonic and first larval instar stages. Overall design: RNA was isolated from N2 and H3.3 null mixed-stage embryos and L1 larvae grown at 20°C using Trizol, in duplicates for all samples. RNA-seq libraries were prepared using the Illumina TruSeq protocol.
Differential Expression of Histone H3.3 Genes and Their Role in Modulating Temperature Stress Response in <i>Caenorhabditis elegans</i>.
Cell line, Subject
View SamplesMyeloid derived suppressor cells (MDSC) playing the immune suppressive roles in tumor bearing host consists of two major subsets of granulocytic and monocytic cells. Granulocytic MDSC (G-MDSC) express CD11b+ Gr-1high Ly6G+ Ly6Clow and produce high level of reactive oxygen species (ROS). Interestingly, neutrophils are well known ROS producing cells during immune defensive process and share same surface markers with G-MDSC. These similar features always brought the fundamental questions whats the difference between G-MDSC and neutrophils but its not yet proven clearly.
Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice.
Sex, Specimen part
View SamplesLamina propria and muscularis macrophages, were sorted at steady steate and 2h after oral exposure to an attenuated form of Salmonella, comparison among these populations showed that the muscularis macrophages quckly respond to the presence of intestinal bacteria, upregulating some important tissue protective genes. Overall design: intestinal macrophages from 3 mice were pooled into one RNA sample, the experiment was done control X infected and was repeated twice
Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages.
Specimen part, Cell line, Subject
View SamplesThe ability for cut tissues to join together and form a chimeric organism is a remarkable property of many plants, however, grafting is poorly characterized at the molecular level. To better understand this process we monitored genome-wide temporal and spatial gene expression changes in grafted Arabidopsis thaliana hypocotyls. Tissues above and below the graft rapidly developed an asymmetry such that many genes were more highly expressed on one side than the other. This asymmetry correlated with sugar responsive genes and we observed an accumulation of starch above the graft that decreased along with asymmetry once the sugar-transporting vascular tissues reconnected. Despite the initial starvation response below the graft, many genes associated with vascular formation were rapidly activated in grafted tissues but not in cut and separated tissues indicating that a recognition mechanism activated that was independent of functional vascular connections. Auxin which is transported cell-to-cell, had a rapidly elevated response that was symmetric, suggesting that auxin was perceived by the root within hours of tissue attachment to activate the vascular regeneration process. A subset of genes were expressed only in grafted tissues, indicating that wound healing proceeded via different mechanisms depending on the presence or absence of adjoining tissues. Such a recognition process could have broader relevance for tissue regeneration, inter-tissue communication and tissue fusion events. Overall design: We analyzed the poly-adenylated transcriptomes of Arabidopsis thaliana hypocotyle tissue during grafting. Our dataset contains 82 strand-specific samples, whereas each condition is represented by two biological replicates.
Transcriptome dynamics at <i>Arabidopsis</i> graft junctions reveal an intertissue recognition mechanism that activates vascular regeneration.
Subject
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