Abstract: The invention relates to the production of secondary metabolites by fungi. More particularly, the invention relates to improvement of production of commercially important secondary metabolites by fungi. The invention provides methods for improving secondary metabolite production in a fungus, comprising modulating the expression of a gene involved in regulation of secondary metabolite production.

Abstract: The present invention relates to a substantially pure population of viable pancreatic progenitor cells, and methods for isolating such cells. The present invention further concerns certain therapeutic uses for such progenitor cells, and their progeny.

Abstract: A primary object of this invention is to provide a method which will enable to coexpress simultaneously two (or more) desired genes in plant, animal or yeast cells, in transgenic plants and animals, or in vitro, in plant cell-derived or animal cell-derived translation systems. This objection is to be accomplished by utilizing sequence elements derived from RNAs of a tobamovirus upstream of MP gene or CP gene termed here as IRESMP and IRESCP , respectively. The method of this invention involves the construction of a recombinant nucleic acid sequence which comprises a specific transcriptional promoter, a first gene expressible in eukaryotic cells linked to said transcriptional promoter, IRESMP or IRESCP located 3? to the first gene and a second gene expressible in eukaryotic cells, located 3? to IRES sequence such that the second gene is placed under the transcriptional control of IRES sequence originated from tobamovirus genome.

Abstract: This invention demonstrates the utility of a yeast expression system for the expression of functional heterologous multi-domain proteins in yeast. The yeast expression system allows for the inclusion of a plurality of (up to three) modular expression cassettes which may encode multiple polypeptide chains of a heterologous multi-domain protein on a single plasmid (Twin Cassette). Because multiple polypeptide chains may be encoded for by the expression cassettes of the present invention in a single vector, the system can produce equivalent amounts of the multiple polypeptide chains, thereby enhancing the yield of a functional heterologous multi-domain protein. For example, functional monoclonal antibodies (MAbs) comprising a heavy chain and a light chain of an immunoglobulin (IgG), and functional immunotoxins comprising an antibody domain and an oxidase toxin may be produced using the Yeast expression system of the present invention.

Abstract: The present invention provides methods for inducing insulin gene expression in cultured pancreas cells, the method comprising contacting a culture of endocrine pancreas cells expressing a PDX-1 gene and a NeuroD/BETA2 gene with a GLP-1 receptor agonist, wherein the cells have been cultured under conditions such that the cells are in contact with other cells in the culture, thereby inducing insulin gene expression in the cells. The invention also provides high throughput screening methods for modulators of ?-cell function, stable cultures of cells made by the methods of the invention, and methods of treating a human subject using the methods of the invention.

Abstract: A method of introducing a property of a particular yeast strain, based on a recessive allele, into the genetic background of an industrial baker's yeast; as well as yeast strains obtainable according to the method. In particular, a method is disclosed to introduce an lti-property into the genetic background of industrial baker's yeast. The novel strains obtained according to the method may be used for the preparation of a dough and for the manufacture of baked products therefrom, such as on an industrial scale.

Abstract: The invention provides methods of determining the presence of a nuclear localization signal and/or the presence of a nuclear export signal in a protein of interest. The invention further provides chimeric nucleic acids and recombinant host cells for use in such methods. Additionally provided is a nucleic acid molecule encoding a modified LexA protein, wherein the modified LexA protein has no nuclear localization signal, as well as the modified LexA protein itself. In the nuclear import assay, if a protein of interest fused to a mLexA-Gal4AD hybrid contains a functional NLS, the fusion product will enter the yeast cell nucleus and activate the expression of reporter genes. In the nuclear export assay, if a protein of interest fused to a mLexA-SV40 NLS-Gal4AD hybrid contains a functional NES, the fusion product localized to the cell nucleus will exit into the cytoplasm, decreasing the reporter gene expression levels.

Abstract: The present invention relates generally to methods and compositions for the identification of differential protein expression patterns and concomitantly the active genetic regions that are directly or indirectly involved in different tissue types, disease states, or other cellular differences desirable for diagnosis or for targets for drug therapy.

Abstract: We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins and disclose methods and materials for using that procedure to regulatably initiate cell-specific apoptosis (programmed cell death) in genetically engineered cells

Abstract: The invention provides a novel protein that, when expressed in a host cell, increases cellular biomass and cellular protein production and secretion. The invention also provides a polynucleotide encoding the novel protein, and methods for using the polynucleotide and encoded protein to increase cellular biomass and cellular protein production and secretion. Also provided is a genetically altered mutant cell strain with enhanced production and secretion of cellular and heterologous proteins.

Abstract: Disclosed are variants of Cre recombinase that have broadened specificity for the site of recombination. Specifically, the disclosed variants mediate recombination between sequences other than the loxP sequence and other lox site sequences on which wild type Cre recombinase is active. In general, the disclosed Cre variants mediate efficient recombination between lox sites that wild type Cre can act on (referred to as wild type lox sites), between variant lox sites not efficiently utilized by wild type Cre (referred to as variant lox sites), and between a wild type lox site and a variant lox site. Also disclosed are methods or recombining nucleic acids using the disclosed Cre variants. For example, the disclosed Cre variants can be used in any method or technique where Cre recombinase (or other, similar recombinases such as FLP) can be used.

Abstract: The present invention provides methods for inducing insulin gene expression in cultured pancreas cells, the method comprising contacting a culture of endocrine pancreas cells expressing a PDX-1 gene with a GLP-1 receptor agonist, wherein the cells have been cultured under conditions such that the cells are in contact with other cells in the culture, thereby inducing insulin gene expression in the cells. The invention also provides high throughput screening methods for modulators of ?-cell function, stable cultures of cells made by the methods of the invention, and methods of treating a human subject using the methods of the invention.

Abstract: This invention provides methods for cytoplasmic detection of protein—protein interactions, nuclear export/localization sequences, and galactose-independent inducible Gal4p-mediated gene expression through the utilization of GAL regulatory factor, Gal80p, and the yeast galactose regulon.

Abstract: This invention relates to non-radioactive markers that facilitate the detection and analysis of nascent proteins translated within cellular or cell-free translation systems. Nascent proteins containing these markers can be rapidly and efficiently detected, isolated and analyzed without the handling and disposal problems associated with radioactive reagents. Preferred markers are dipyrrometheneboron difluoride (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dyes.

Abstract: Novel synthetic leader peptides have been identified. The leader peptides have use in a method of enhancing the secretion of a recombinant polypeptide produced in a host cell. Polynucleotides encoding the novel leader peptides and a method of designing the polynucleotides are described.

Abstract: The invention provides composition and methods for producing proteins of interest which comprise at least one disulfide bond, include proteins which in their mature form do not contain disulfide bonds, but whose precursor molecule contained at least one disulfide bond. The methods employ a host cell modified to more efficiently produce properly folded disulfide bond containing proteins. The host cells generally contain a mutation in one or more reductase genes, and can be further genetically modified to increase their growth rate, and are further optionally modified to increase the expression of a catalyst of disulfide bond formation. Host cells, methods for using such to produce proteins of interest, proteins of interest produced by these methods are within the scope of the invention.

Abstract: The present invention is directed to herbicide resistant N2 fixing bacteria. The bacteria are useful for effecting N2 fixation, nodulation, growth and yield of herbicide resistant or tolerant leguminous plants treated with herbicide. The bacteria are particularly useful for providing competitive advantage to superior N2 fixing rhizobial strains over non-resistant indigenous rhizobia for nodulation of herbicide resistant or tolerant leguminous plants.

Abstract: The present invention provides RNA purification and/or analysis methods that use ammonium sulfate to mitigate or neutralize inhibitory effects of certain molecules. Exemplary inhibitory molecules that interfere with RNA function or analysis are those that bind to or cleave RNA, or stabilize RNA secondary structures.

Abstract: The present invention defines a DNA: protein-binding assay useful for screening libraries of synthetic or biological compounds for their ability to bind DNA test sequences. The assay is versatile in that any number of test sequences can be tested by placing the test sequence adjacent to a defined protein binding screening sequence. Binding of molecules to these test sequence changes the binding characteristics of the protein molecule to its cognate binding sequence. When such a molecule binds the test sequence the equilibrium of the DNA:protein complexes is disturbed, generating changes in the concentration of free DNA probe. Numerous exemplary target test sequences (SEQ ID NO:1 to SEQ ID NO:600) are set forth. The assay of the present invention is also useful to characterize the preferred binding sequences of any selected DNA-binding molecule.

Abstract: An in-vitro system in which mammalian messenger RNA decapping occurs is provided, for use in identifying modulators, deficiencies, and other aspects of the regulation of RNA turnover.