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SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy
Small molecules that alter splicing of a specific messenger RNA have beneficial effects in a model of a motor neuron disease and selective SMN2 splicing modifiers may have therapeutic potential for patients with SMA. Expand
Genome-based analysis of the nonhuman primate Macaca fascicularis as a model for drug safety assessment.
The genome sequence of a long-tailed macaque female of Mauritian origin is determined using a whole-genome shotgun sequencing approach and allows high-resolution genotyping and microarray-based gene-expression profiling for animal stratification, thereby allowing the use of well-characterized animals for safety testing. Expand
Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients
Circulating tumor DNA (ctDNA) is a new circulating tumor biomarker which might be used as a prognostic biomarker in a way similar to circulating tumor cells (CTCs). Here, we used the high prevalenceExpand
Solution structure of polytheonamide B, a highly cytotoxic nonribosomal polypeptide from marine sponge.
The three-dimensional structure of pTB is determined by NMR spectroscopy, structure calculation, and energy minimization and indicates that pTB molecules form transmembrane channels that permeate monovalent cations as gramicidin A channels do. Expand
Intrahepatic Transcriptional Signature Associated with Response to Interferon-α Treatment in the Woodchuck Model of Chronic Hepatitis B
By studying recombinant IFN-α in a fully immunocompetent animal model of CHB, it is determined that the immunomodulatory effects, but not the direct antiviral activity, of this pleiotropic cytokine are most closely correlated with treatment response. Expand
Functional analysis and transcriptional output of the Göttingen minipig genome
A new chromosome level based version of the Göttingen minipig genome is presented together with a comparative transcriptional analysis of tissues with pharmaceutical relevance as basis for translational research and high conservation of gene expression signatures in 13 tissues with biomedical relevance between humans and adult minipigs is shown. Expand
The beta(E)-domain of wheat E(c)-1 metallothionein: a metal-binding domain with a distinctive structure.
The NMR solution structure of the beta(E)-domain of the early cysteine-labeled protein from wheat is shown, which represents the first three-dimensional structure of a plant MT, and backbone dynamics investigated by (15)N relaxation experiments support the results of the structure determination. Expand
Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers
Evidence is provided that SMN2 mRNA forms a ribonucleoprotein complex that can be specifically targeted by these small molecules, and has wide-ranging implications in understanding how small molecules can interact with specific quaternary RNA structures. Expand
A novel orally available small molecule that inhibits hepatitis B virus expression.
RG7834 can potentially provide anti-HBV benefits and increase HBV cure rates, by direct reduction of viral agents needed to complete the viral life cycle, as well as a reduction ofiral agents involved in evasion of the host immune responses. Expand
Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes
This study validates TSL2 as a target for small-molecule drug discovery in SMA, identifies a novel mechanism of action for an E7 splicing modifier, and sets a precedent for other splicing-mediated diseases where RNA structure could be similarly targeted. Expand