Abstract: The invention provides methods for identifying modulators of RETindependent, GDNF effected intracellular signaling. The invention further provides methods of identifying useful modulators of RET-independent GDNF receptoreffected MET activation, as well as modulators of morphological responses which are effected by nonRET GDNF receptor-effected intracellular signaling. Methods of distinguishing RET-independent GDNF ligand-mediated intracellular signaling by different cellular GDNF receptors from RET-dependent intracellular signaling are provided. The methods of the invention also provide an understanding of the complex interrelationships between RET, MET, GFRa in response to GDNF ligands.

Abstract: The present invention relates to an in vitro method for identifying a molecule, which interferes with the interaction between a glial cell-line derived neurotrophic factor family ligand (GFL) and a heparan sulfate proteoglycan (HSPG), by screening a library of molecules against a matrix anchored complex comprising at least one immobilized glial cell-line derived neurotrophic factor family ligand (GFL) and at least one heparan sulfate proteoglycan (HSPG), wherein the interfering molecule is isolated based on its capacity to replace a glial cell-line derived neurotrophic factor family ligand (GFL) in said anchored complex. The invention also relates to a complex for identifying such a molecule. The invention also relates to methods for preventing or delaying a neurodegenerative process as well as to method for prophylactic treatment or treatment of a disorder in the nervous system.

Abstract: The present invention provides compounds having a chelating moiety and an oligonucleotide sequence wherein the oligonucleotide includes one or more modified nucleobases, such as hydroxynucleobases. The disclosed compounds are suitable for antisense therapy. The chelating moiety can be complexed to an ion of a lanthanide metal. These compounds are efficient translation inhibitors of nucleic acids and have increased binding affinity for target nucleic acids. The invention also includes compositions and methods of using these compositions as antisense therapy.

Abstract: The present invention discloses a novel neurotrophic factor protein, MANF2 and a genetic sequence encoding the same. The molecule will be useful in the development of a range of therapeutics and diagnostics useful in the treatment, prophylaxis and/or diagnosis of MANF2 dependent conditions. The molecule of the present invention is also a useful effector of primary and central neurons, especially dopaminergic neurons at the central nervous system and growth factor genes.

Abstract: The present invention discloses a novel neurotrophic factor protein, MANF2 and a genetic sequence encoding the same. The molecule will be useful in the development of a range of therapeutics and diagnostics useful in the treatment, prophylaxis and/or diagnosis of MANF2 dependent conditions. The molecule of the present invention is also a useful effector of primary and central neurons, especially dopaminergic neurons at the central nervous system and growth factor genes.

Abstract: The invention provides methods and compositions for identifying agents which modulate cell death, indicated e.g. by the expression of caspase-2 and/or caspase-7, in GDNF family growth factor deprived neuronal or nonneuronal cells. The methods for identifying such agents find particular application in drug development.

Abstract: Methods for screening for agonists and antagonists of GPI-anchored independent intracellular signaling resulting in [Ca2+]i elevation, ERK1, ERK2 and CREB phosphorylation, and Src family kinase activation are described, as well as methods for treatment involving administration of agonists/antagonists of such signaling.

Abstract: Receptors for Glial Cell Line-Derived Neurotrophic Factor (GDNF), their cellular expression, isolation, biochemical characterization, and sequences are disclosed. c-RET is disclosed as one receptor for GDNF; additional novel receptors are also disclosed. The preparation of monoclonal antibodies directed against GDNF is also disclosed.

Abstract: Receptors for Glial Cell Line-Derived Neurotrophic Factor (GDNF), their cellular expression, isolation, biochemical characterization, and sequences are disclosed. c-RET is disclosed as one receptor for GDNF; additional novel receptors are also disclosed. The preparation of monoclonal antibodies directed against GDNF is also disclosed.

Abstract: The present invention is related to the use of nucleotide sequences substantially similar to the cDNA sequence (SEQ ID NO:2:) obtainable from the leader sequence (SEQ ID NO:1:) of the Cocksfoot mottle virus (CfMV) which is capable of enhancing protein synthesis and expression of proteins, especially in plants such as cereals. Also disclosed is a method for producing potential enhancer elements by selecting 5′UTRs having a capacity of producing hairpin loop structures and preparing substantially similar nucleic acid sequences. In addition a method for enhancing the expression in plants as well as the properties characteristic for the nucleotide sequence which are responsible for the enhanced expression.

Abstract: Methods for preventing or treating damage to sensory hair cells and cochlear neurons are disclosed. The methods comprise the administration of an effective amount of a compound of Formula I or Formula II. The method provides for the prevention/treatment of both hearing loss and loss of the sense of balance.

Abstract: Methods for preventing or treating damage to sensory hair cells and cochlear neurons are disclosed. The methods comprise the administration of an effective amount of a compound of Formula I or Formula II. The method provides for the prevention/treatment of both hearing loss and loss of the sense of balance.

Abstract: The effect of GDNF on kidney morphogenesis is disclosed. Methods for stimulating budding and branching of the ureteric epithelium, for stimulating axonal outgrowth, for maintaining ureteric epithelial cells in culture, for preventing apoptosis of ureteric epithelial cells, and for treating diseases using GDNF are also disclosed.

Abstract: This invention discloses transgenic plants, such as transgenic tobacco and potato, having resistance to multiple viral taxonomic groups using parts of the 2,5A oligoadenylate pathway. In particular, said plants are genetically engineered to contain a DNA sequence encoding at least one polypeptide having a 2,5A synthetase activity. By this means a step in the 2,5A oligoadenylate pathway heretofore believed to be missing in all plants is provided so that viral infection in the transgenic plants is inhibited via a 2,5A dependent endonuclease. Moreover, this invention relates to a process for the production of said transgenic plants by transfection with a genetically engineered DNA sequence encoding at least one polypeptide having a 2,5A synthetase activity.