Abstract: The invention provides methods and compositions for inhibiting pathogenic binding of an pathogenic autoantibody to a myelin oligodendrocyte glycoprotein (MOG) autoantigen and screening for inhibitors of pathogenic binding of an autoantibody to a MOG autoantigen.

Abstract: The invention provides methods and compositions for inhibiting autoantibody binding in demyelinating disease such as multiple sclerosis. The compositions comprise immunoglobulin CDR3 sequences derived from combinatorial phage display libraries selected for high-affinity binding to myelin oligodendrocyte glycoprotein.

Abstract: The invention provides methods and compositions for screening for pharmacological agents which regulate gene expression in mammals. An exemplary assay involves (a) contacting a mammalian cell comprising a knock-in mutant of a targeted native allele encoding a reporter of gene expression, wherein the expression of the reporter is under the control of the gene expression regulatory sequences of the native allele, with a candidate agent under conditions whereby but for the presence of the agent, the reporter is expressed at a first expression level; and, (b) measuring the expression of the reporter to obtain a second expression level, wherein a difference between the first and second expression levels indicates that the candidate agent modulates gene expression.

Abstract: The invention provides methods and compositions for assaying hypoxia-inducible factor (HIF) prolyl hydroxylation. Subject assays may be cell-based or in vitro, and comprise incubating a mixture comprising an isolated or recombinantly expressed HIF-specific prolyl hydroxylase (HPH), and a substrate of the hydroxylase, under conditions whereby the hydroxylase prolyl hydroxylates the substrate, and detecting a resultant prolyl hydroxylation of the substrate. The mixture may also comprise a candidate agent which modulates the resultant prolyl hydroxylation. In particular embodiments, the hydroxylase is selected from the group consisting of human HPH1, HPH2 and HPH3, and/or the substrate comprises LAPY, wherein P is hydroxylated by the hydroxylase.

Abstract: The invention provides methods and compositions relating to cholesterol 25-hydroxylase polypeptides having cholesterol 25-hydroxylase-specific structure and activity, related polynucleotides and modulators of cholesterol 25-hydroxylase function and serum cholesterol. The invention provides isolated cholesterol 25-hydroxylase hybridization probes and primers capable of specifically hybridizing with natural cholesterol 25-hydroxylase genes, cholesterol 25-hydroxylase-specific binding agents such as specific antibodies, agonists and antagonists, and methods of making and using the subject compositions in diagnosis (e.g. genetic hybridization screens for cholesterol 25-hydroxylase transcripts), therapy (e.g. cholesterol 25-hydroxylase inhibitors to modulate serum cholesterol) and in the biopharmaceutical industry (e.g. as immunogens, reagents for isolating natural 25-hydroxylase genes and transcripts, reagents for screening chemical libraries for lead pharmacological agents, etc.).

Abstract: The invention provides methods and compositions of selectively disrupting mitotic function in a target cell demonstrating undesirable mitotic function. Suitable target cells include mammalian, plant and bacterial cells, which cells may be in vitro or in situ. The general methods involve introducing into the target cell an effective amount of a peptide comprising contiguous acidic amino acids, such as Asp or Glu, whereby the undesirable mitotic function of the cell is selectively disrupted. In particular embodiments, the peptide comprises a Gm2S-1 peptide, particularly a lunasin and/or alisin peptide. The peptide may be introduced by transfecting the cell with a nucleic acid encoding the peptide.

Abstract: The invention provides methods and compositions relating to human polypeptide activators of caspases such as polypeptide and polynucleotide sequences diagnostic of caspase activators. These sequences and polypeptides and polynucleotides embodying these sequences find a wide vanety of diagnostic and therapeutic applications involving detecting and/or modulating expression and/or function of activators or caspases or genes or transcripts encoding such activators and generating genetic and immuno probes specific to activators of caspases.

Abstract: The present invention provides isolated nucleic acid sequences which encode a family of HMG-CoA Reductase Degradation (HRD) polypeptides. More particularly, the present invention provides isolated HRD1, HRD2 and HRD3 nucleic acids and the Hrd polypeptides encoded by such nucleic acids, i.e., Hrd1, Hrd2 and Hrd3, respectively. Vectors comprising the nucleic acids are provided. In addition, the present invention provides screening assay related to cholesterol biosynthesis.

Abstract: Methods and composition for inducing, detecting and modulating seizure in animal systems are provided. Methods for inducing seizure comprise (1) electrically stimulating an unanesthetized fly and detecting seizure induction in the fly (2) electrically stimulating a fly with less than 10V and detecting seizure induction in the fly; (3) electrically stimulating a population of wild-type flies and detecting seizure induction in most of the flies and (4) electrically stimulating a population of flies and quantitatively detecting seizure induction in the flies across genotypes or experience. Methods for modulating seizure induction comprise changing the activity of a novel seizure regulator in an animal system and confirming a resultant change in seizure inducibility of the system.

Abstract: The invention relates to methods, cells and nucleic acids for making transgenic animals. The methods generally comprise introducing into a genome of an animal a genetic construct comprising a transcriptional regulatory element operably linked to a heterologous marker gene encoding a marker, wherein the element drives expression of the marker across genera transgenic in the construct sufficient to visually detect the marker in photoreceptive cells or organs, and selecting for transgenesis by visually detecting the marker in a photoreceptive cell or organ of the animal.

Abstract: The present invention provides a method and a composition for detecting the levels of a plurality of biomolecular probes in a sample. In particular, the invention relates to a hybridization composition for detecting the presence or levels of different polynucleotide sequences in a sample.

Abstract: The invention provides methods and compositions relating to DNA Fragmentation Factor (DFF) polypeptides and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed DFF encoding nucleic acids or purified from human cells. The invention provides isolated DFF hybridization probes and primers capable of specifically hybridizing with the disclosed DFF genes, DFF-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Abstract: Bifunctional green fluorescent protein (GFP)-annexin fusion proteins combine the inherent strong visible fluorescent properties of GFPs with the anionic phospholipid binding specificity of annexins. Recombinant host cells, especially bacteria, are used to efficiently express the fusion proteins in high yield and soluble form, suitable for rapid, one-step affinity purification. Uses include of selective cellular and biochemical labeling, particularly anionic species, such as selectively labeling apoptotic cells.

Abstract: The invention provides methods and compositions for promoting neural cell growth and/or regeneration. The general methods involve contacting with an activator of a cyclic nucleotide dependent protein kinase a neural cell subject to growth repulsion mediated by a neural cell growth repulsion factor. The activator may comprise a direct or an indirect activator of the protein kinase; the repulsion factor typically comprises one or more natural, endogenous proteins mediating localized repulsion or inhibition of neural cell growth; and the target cells are generally vertebrate neurons, typically injured mammalian neurons. The subject compositions include mixtures comprising a neural cell, an activator of a cyclic nucleotide dependent protein kinase and a neural cell growth repulsion factor.

Abstract: Specific BRCA1 mutations, PCR primers and hybridization probes are used in nucleic acid-based methods for diagnostic of inheritable breast cancer susceptibility. Additionally, binding agents, such as antibodies, specific for peptides encoded by the subject BRCA1 mutants are used to identify expression products of diagnostic mutations/rare alleles in patient derived fluid or tissue samples. Compositions with high binding affinity for transcription or translation products of the disclosed BRCA1 mutations and alleles are used in therapeutic intervention. Such products include anti-sense nucleic acids, peptides encoded by the subject nucleic acids, and binding agents such as antibodies, specific for such peptides.

Abstract: Methods for enhancing the production of interferon in animal cell culture are described. These methods rely on the manipulation of the cellular levels of certain inducers of interferon production, in particular cellular levels of double-stranded-RNA-dependent kinase (dsRNA-PKR, or PKR). In cell cultures that overproduce PKR, interferon synthesis is induced to high levels, and significant amounts of interferon can be recovered without conventional induction of interferon by virus.

Abstract: The invention provides methods and compositions relating to an I&kgr;B kinase, IKK-&agr;, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IKK-&agr; encoding nucleic acids or purified from human cells. The invention provides isolated IKK-&agr; hybridization probes and primers capable of specifically hybridizing with the disclosed IKK-&agr; genes, IKK-&agr;-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Abstract: The invention provides computational methods and compositions for identifying polymorphic repeats in genes. Candidate polymorphic repeats are identified by detecting tandem repeats in a target coding sequence, scoring the repeats for polymorphic probability, and generating a dataset correlating the repeats with polymorphic probability. Actual polymorphic repeat are identified by further detecting the candidate polymorphic repeat in each of a population of different coding sequences, and determining whether the candidate polymorphic repeat is polymorphic in the population. Computationally derived polymorphic repeats are validated with phenotypic variations and these correlates are used to detect the presence or absence of such phenotypic variation in test genes. Variances at polymorphic repeats are identified by detecting in a test gene or coding region the presence or absence of variance at a disclosed unconventional polymorphic repeat.

Abstract: The invention discloses methods for effecting the production of recombinant mammalian procollagen in yeast, as well as compositions comprising yeast cells cap producing mammalian procollagen.

Abstract: Low density lipoprotein receptor (LDRL) adaptin is a novel, key component of human cholesterol regulation, which provides a target for rational drug design and screening, therapeutic intervention, and diagnosis. Disclosed reagents include a variety of LDLR adaptin and LDLR adaptin PTB and CC domain compositions, including in vitro compositions comprising a natural human LDLR adaptin PTB domain and a ligand such as an NPXY (SEQ ID NO:7) peptide. These LDLR adaptin reagents are used, inter alia, in rational drug screening methods. The invention also provides polynucleotides encoding the subject LDLR adaptin polypeptides, including natural coding sequences, which may be used as probes or primers for detecting or amplifying LDLR adaptin genes and transcripts.