Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.

Abstract: A method that includes measuring the expression level of at least one transposon in a biological sample from a subject; and determining whether the measured transposon expression exceeds a predetermined level, and if so, administering to the subject a transposon inhibitor in an amount effective to reduce the expression level of a transposon.

Abstract: A method for obtaining from genomic material genomic copy number information unaffected by amplification distortion, comprising obtaining segments of the genomic material, tagging the segments with substantially unique tags to generate tagged nucleic acid molecules, such that each tagged nucleic acid molecule comprises one segment of the genomic material and a tag, subjecting the tagged nucleic acid molecules to amplification by polymerase chain reaction (PCR), generating tag associated sequence reads by sequencing the product of the PCR reaction, assigning each tagged nucleic acid molecule to a location on a genome associated with the genomic material by mapping the subsequence of each tag associated sequence read corresponding to a segment of the genomic material to a location on the genome, and counting the number of tagged nucleic acid molecules having a different tag that have been assigned to the same location on the genome, thereby obtaining genomic copy number information unaffected by amplification d

Abstract: The present invention relates to transposon activation and mobilization, particularly in the brain, during normal aging; reporter systems to detect such mobilization, along with cells and transgenic animals containing such systems; methods of monitoring neuronal function during normal aging; methods of determining the risk of age-related neuronal decline and age-related mortality; and the use of transposon inhibitors and apoptosis inhibitors to delay age-related neuronal decline and age-related mortality.

Abstract: The present invention provides methods of treating cognitive deficits associated with mental retardation. The methods comprise combining cognitive training protocols and a general administration of phosphodiesterase 4 inhibitors.

Abstract: A method for obtaining from genomic material genomic copy number information unaffected by amplification distortion, comprising obtaining segments of the genomic material, tagging the segments with substantially unique tags to generate tagged nucleic acid molecules, such that each tagged nucleic acid molecule comprises one segment of the genomic material and a tag, subjecting the tagged nucleic acid molecules to polymerase chain reaction (PCR) amplification, generating tag associated sequence reads by sequencing the product of the PCR reaction, assigning each tagged nucleic acid molecule to a location on a genome associated with the genomic material by mapping the subsequence of each tag associated sequence read corresponding to a segment of the genomic material to a location on the genome, and counting the number of tagged nucleic acid molecules assigned to the same location on the genome having a different tag, thereby obtaining genomic copy number information unaffected by amplification distortion.

Abstract: The present disclosure provides methods and compositions for genetic transformation of Lemnaceae species.

Abstract: The present disclosure relates to compositions and methods for inhibiting nonsense-mediated mRNA decay in a gene-specific manner, for example in the treatment of diseases or disorders caused by nonsense mutations.

Abstract: The present invention provides compounds and methods for modulating target nucleic acids found in organelles or sub-organelles of cells. The invention includes, but is not limited to compounds and methods that modulate target nucleic acids in a sub-nuclear organelle, such as the nucleolus and/or a cajal body. In certain embodiments, the cell is in an animal.

Abstract: Described herein are enhanced N-methyl-D-aspartate (NMDA) receptor antagonists, pharmaceutical compositions thereof, and their methods of use and treatment, e.g., of Formula (I): wherein one or more of R1, R2, R3, R4, R5, or the ring formed by the joining of R1 and R2, is a hydrophobic moiety which confers enhanced antagonist activity as compared to existing NMDA receptor antagonists, e.g., ifenprodil. Compounds described herein are designed based on the discovery that ifenprodil binds within the allosteric domain of the GluN1/GluN2B NMDA receptor, particularly at the interface between GluN1 and GluN2B subunits. In silico methods are further described herein.

Abstract: This disclosure relates to methods and compositions useful for treating Alzheimer's disease. In particular, the disclosure relates to pharmaceutical compositions containing an EGFR-inhibitory compound suitable for administration to treat Alzheimer's disease, as well as to related therapeutic methods. In addition, this disclosure relates to screening methods for identifying compounds useful for treating Alzheimer's disease based on the ability to inhibit the activity of EGFR.

Abstract: The present invention provides methods of treating cognitive deficits associated with mental retardation. The methods comprise combining cognitive training protocols and a general administration of phosphodiesterase 4 inhibitors.

Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a cell, tissue or animal. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.

Abstract: Provided herein are genetically-altered Solanaceae plants, compositions related to the Solanaceae plants, and methods of making the Solanaceae plants.

Abstract: The invention relates to the isolation and characterization of a maize gene, RAMOSA3 (RA3), responsible for meristem development and inflorescence development including branching. The gene, gene product, and regulatory regions may be used to manipulate branching, meristem growth, inflorescence development and arrangement, and ultimately to improve yield of plants. The invention includes the gene and protein product as well as the use of the same for temporal and spatial expression in transgenic plants to alter plant morphology and affect yield in plants. The invention also includes the gene and protein product for SISTER OF RAMOSA3 (SRA).

Abstract: The present invention provides compounds comprising oligonucleotides complementary to a pyruvate kinase M transcript. Certain such compounds are useful for hybridizing to a pyruvate kinase M transcript, including but not limited to a pyruvate kinase M transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the pyruvate kinase M transcript. In certain embodiments, such compounds are used to treat one or more symptoms associated with cancer.

Abstract: Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Ago2 because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.

Abstract: Described herein are agents, including antibodies, antibody fragments, polypeptides and organic small molecules, that bind reversibly inactive PTP1B (designated herein in the alternative as PTP1B-SN or PTP1B-OX) and stabilize it (stabilize PTP1B-OX) in such a manner that they inhibit reactivation of reversibly oxidized, inactive PTP1B by reduction (by reducing agent) and have no substantial direct inhibitory effect on phosphatase activity/PTP1B activity (for example, as detectable in assays in vitro).

Abstract: Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Ago2 because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.

Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.