Abstract: The disclosure features compositions and methods for ameliorating cognitive impairments associated with neuropsychiatric disorders, particularly those associated with anterodorsal (AD) thalamus hyperexcitability in the brain of a subject. Various embodiments of the disclosure provide for personalized and targeted therapeutic approaches for screening, diagnosing, preventing, and treating cognitive impairments and neuropsychiatric disorders.

Abstract: The present application provides an anti-side-rolling damping vehicle-end device and a rail vehicle. The anti-side-rolling damping vehicle-end device comprises: a pair of damping mechanisms, which are adapted to respectively being installed on a pair of end walls of a pair of connected vehicle bodies that are arranged opposite each other, the pair of damping mechanisms being arranged on two sides of the axis of the vehicle bodies in a lengthwise direction, respectively; and a connecting rod, wherein two ends of the connecting rod are hinged to the pair of damping mechanisms, respectively, and the length of the connecting rod is greater than a vertical movement displacement of any vehicle body, such that side-rolling movement and vertical movement of the vehicle body is decoupled.

Abstract: The present disclosure relates to compositions and methods for treating Williams syndrome (WS), herein identified as a neurodevelopmental oligodendrocyte hypomyelination-associated disease, and to compositions and methods for treatment of other neurodevelopmental myelination abnormality diseases or disorders.

Abstract: Aspects of the disclosure relate to non-naturally occurring polynucleotides encoding a Shank3 protein, AAV vectors comprising the polynucleotides, and gene therapy methods.

Abstract: The present disclosure relates to compositions and methods for treating Williams syndrome (WS), herein identified as a neurodevelopmental oligodendrocyte hypomyelination-associated disease, and to compositions and methods for treatment of other neurodevelopmental myelination abnormality diseases or disorders.

Abstract: The present disclosure provides compositions and methods for minimally invasive optogenetic stimulation. More particularly, the present disclosure provides compositions and methods for using an ultra-sensitive step-function opsin for minimally invasive optogenetic stimulation.

Abstract: Described herein are methods of enhancing chromosomal homologous recombination to stimulate a loss of heterozygosity at a gene locus of interest in a living cell. These methods are driven by an enhancer component and a target-specific endonuclease component and proceed through a mechanism whereby: exogenous donor DNA that is homologous to the gene locus of interest is not introduced into the living cell; the desired allele of the gene locus of interest remains uncleaved; and the undesired allele is either uncleaved, cleaved at a single location, or cleaved at multiple locations. These methods have numerous applications, including the repair of risk alleles for disease prevention, the correction of heterozygous mutations in dividing cells, the design of cancer therapeutics, and the design of novel gene-drive strategies.

Abstract: Provided herein are methods for treating a disorder associated with a sleep spindle deficit using a group II metabotropic glutamate receptor modulator.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: The present disclosure relates to compositions and methods for treating Williams syndrome (WS), herein identified as a neurodevelopmental oligodendrocyte hypomyelination-associated disease, and to compositions and methods for treatment of other neurodevelopmental myelination abnormality diseases or disorders.

Abstract: Described herein are methods of enhancing chromosomal homologous recombination to stimulate a loss of heterozygosity at a gene locus of interest in a living cell. These methods are driven by an enhancer component and a target-specific endonuclease component and proceed through a mechanism whereby: exogenous donor DNA that is homologous to the gene locus of interest is not introduced into the living cell; the desired allele of the gene locus of interest remains uncleaved; and the undesired allele is either uncleaved, cleaved at a single location, or cleaved at multiple locations. These methods have numerous applications, including the repair of risk alleles for disease prevention, the correction of heterozygous mutations in dividing cells, the design of cancer therapeutics, and the design of novel gene-drive strategies.

Abstract: The present invention relates to in vitro models of autism and methods of using the same to diagnose disorders associated with network dysfunction, e.g., autism schizophrenia, depression, obsessive-compulsive spectrum disorders, bipolar disorder, or epilepsy, and to identify compounds for use in treating these conditions.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: Provided herein are methods and compositions for identifying subjects as having an elevated risk of developing or having a neuropsychiatric disorder. These subjects are identified based on the presence of one or more mutations.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: Transgenic non-human mammals and cells having a disruption in at least one allele of nArgBP2 are provided. Methods of identifying therapeutic agents for the treatment of a disorder associated with altered expression of nArgBP2 are also provided. Methods of assessing the risk of an individual developing a disorder associated with disruption of nArgBP2 and methods of treating individuals with such a disorder are provided.

Abstract: Provided is a transgenic knockout mouse whose genome includes a disruption in its endogenous SAPAP3 gene, wherein the disruption results in the mouse exhibiting increased levels of anxiety as compared to a wild type mouse. Also provided are cells derived from the disclosed transgenic knockout mouse. Also provided are methods of identifying a therapeutic agent for the treatment of an individual diagnosed with anxiety, methods for diagnosing an individual with a clinical disorder associated with reduced expression of a SAPAP3 gene product, and methods for treating an individual with a clinical anxiety disorder associated with reduced expression of a SAPAP3 gene product.

Abstract: Genomic and cDNA clones corresponding to the tipE gen of Drosophila melanogaster are described. The tipE protein functions in concert with the para gene product, a polypeptide which exhibits similarity to mammalian voltage-dependent sodium channel .alpha. subunits but is not by itself functional. Coexpression of the tipE and para genes in a host cell affords functional cation channels. The invention accordingly provides screening assays for modulators of Drosophila cation channels employing cells expressing both tipE and para polypeptides, useful inter alia to evaluate candidate pesticidal agents.

Abstract: DNAs encoding voltage-activated cation channels have been cloned and characterized. The cDNA's have been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells.