This invention relates to polypeptides having aldolase activity, including pyruvate activity such as, without limitation, HMG and/or KHG aldolase activity, polynucleotides encoding these polypeptides, and methods of making and using these polynucleotides and polypeptides. In some embodiments, the invention is directed to polypeptides having aldolase activity, including pyruvate activity such as, without limitation, HMG and/or KHG aldolase activity, including thermostable and thermotolerant activity, and polynucleotides encoding these enzymes, and making and using these polynucleotides and polypeptides. The polypeptides in accordance with the invention can be used in a variety of pharmaceutical, agricultural and industrial contexts. In some embodiments, the invention provides polypeptides and biosynthetic pathways that are useful in the production of R-2-hydroxy 2-(indol-3ylmethyl)-4-keto glutaric acid (R-MP) and certain stereoisomers of monatin, such as R,R and S,R monatin, and salts thereof, as well as certain stereoisomers of monatin derivatives, such as the R,R and S,R configurations, and salts thereof.

The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems.

The invention relates to xylanases and to polynucleotides encoding the xylanases. In addition, methods of designing new xylanases and methods of use thereof are also provided. The xylanases have increased activity and stability at increased pH and temperature.

Four zebrafish gene promoters, which are skin specific, muscle specific, skeletal muscle specific and ubiquitously expressed respectively, were isolated and ligated to the 5′ end of the EGFP gene. When the resulting chimeric gene constructs were introduced into zebrafish, the transgenic zebrafish emit green fluorescence under a blue light or ultraviolet light according to the specificity of the promoters used. Thus, new varieties of ornamental fish of different fluorescence patterns, e.g., skin fluorescence, muscle fluorescence, skeletal muscle-specific and/or ubiquitous fluorescence, are developed.

The present invention provides methods for modulating expression of endogenous cellular genes using recombinant zinc finger proteins.

Disclosed are methods, compositions, and systems for transforming silkworms to produce spider silk and analogs of spider silk. In certain embodiments, the method may include inserting a DNA sequence coding for at least a portion of a spider silk fibroin polypeptide, or an analog of a spider silk fibroin polypeptide, positioned between at least a portion of the 5′ and 3′ ends of a silkworm fibroin gene to generate a fusion gene construct having a sequence that encodes for a polypeptide comprising both spider silk fibroin and silkworm silk fibroin sequences. In certain embodiments, the fused gene is able to replace a native gene present in the silkworm such that the transformed silkworm expresses a polypeptide comprising a spider silk fibroin polypeptide, or an analog thereof, and expresses significantly less of the native silkworm silk.

Certain embodiments are directed to marker peptides or marker peptide antibodies can be used in producing diagnostic kits or used in diagnostic methods for Alzheimer's disease. The antibodies and/or marker peptides can be used in immunohistochemical and biochemical methods for qualitative and quantitative analysis of marker peptide levels and/or localization in brain samples and CSF samples.

Provided herein are compositions and methods for studying cancer therapeutics and etiology, for example, mouse cancer models, cancer cell lines, and uses thereof. Human p53 knock-in (Hupki) mice with a Y220 (e.g., Y220C, Y220H, or Y220S) mutation in p53 are provided. These Hupki-Y220 mice can be used, for example, to examine tumorigenesis in different tissues, investigate mechanisms of gain of function, develop mouse models of cancer, generate cancer cell lines that can be implanted into recipient mice, and test potential therapeutics.

Artificial expression constructs for selectively modulating gene expression in selected central nervous system cell types are described. The artificial expression constructs can be used to selectively express synthetic genes or modify gene expression in excitatory cortical neurons, such as primarily within cortical layers 2/3, 4, 5, and 6 and including those with extratelencephalic (ET) projections, intratelencephalic (IT) projections, and pyramidal tract (PT) projections, among others.

A pharmaceutical composition comprising a canine, feline or equine antibody having a lambda light chain or a functional fragment or functional derivative thereof, and a pharmaceutically acceptable excipient or carrier, for use or suitable for use in the prevention or treatment of disease ion a dog, cat, or horse, respectively.