Abstract: The invention relates to the production of proteins and other substances of interest in saliva of transgenic animals, particularly in mammals that produce large quantities of saliva, particularly monogastric ruminants, and ovine, caprine and bovine mammals. Preferred embodiments of the invention relate in particular to the production of foreign and modified proteins in the transgenic saliva of these animals, including particularly human fibrinogen, human prothrombin and human thrombin, among others. The invention relates as well to methods, devices, genetic constructs and to transgenic constructs for making the proteins and other substances of interest, to novel saliva and saliva-derived compositions, novel products from the saliva, and to uses of the saliva, saliva-derived compositions and novel products.

Abstract: The present invention is in the fields of molecular biology, cell biology, and genetics. The invention is directed generally to mutating genes in cells in vitro and in multi-cellular organisms. The invention encompasses methods for mutating genes in cells using polynucleotides that act as insertional mutagens. Such methods are used to achieve mutation of a single gene to achieve a desired phenotype as well as mutation of multiple genes, required cumulatively to achieve a desired phenotype, in a cell or in a multi-cellular organism. The invention is also directed to methods of identifying one or more mutated genes, made by the methods of the invention, in cells and in multi-cellular organisms, by means of a tagging property provided by the insertional mutagen(s). The insertional mutagen thus allows identification of one or more genes that are mutated by insertion of an insertional mutagen.

Abstract: This disclosure provides improved methods for obtaining populations of dopaminergic neurons from pluripotent stem cells. The process involves taking a population of neural precursor cells derived from a line of human embryonic stem cells, and culturing the cells in a medium that contains a neurotrophin, either cyclic adenosine monophosphate (cAMP) or a compound that elevates intracellular cAMP levels, and optionally an antioxidant such as ascorbic acid. Cell populations have been obtained that contain a high proportion of cells staining for tyrosine hydroxylase, which is a feature of dopaminergic neurons. The neural progenitors and terminally differentiated neurons of this invention can be generated in large quantities for use in drug screening and the treatment of clinically important neurological disorders, such as Parkinson's disease.

Abstract: A plasmid, viral or linear DNA molecule containing a nucleic acid sequence derived from the promoter region of the hCol1?2 gene, which is selectively transported into the nuclei of cells in the osteoblast lineage. The sequence can be used independently as a nuclear entry sequence only, and/or as a nuclear entry sequence without regard to position, in a vector or linear DNA that directs gene expression and nuclear entry. The disclosure further includes a chimeric DNA sequence derived by the addition of osteoblast-specific enhancer sequences to the nuclear entry sequence/promoter sequence, to increase osteoblast-specific expression while retaining osteoblast-specific nuclear import. An enhancer sequence is derived from the promoter region of the human Core Binding Factor alpha 1 (Cbfa1/Runx2) gene. The Cbfa1/Runx2 promoter can be added to the sequence derived from, or alternatively, comprising the promoter region of the hCol1?2 gene. Also provided are methods of use of the novel sequences.

Abstract: The present invention provides compositions and methods for direct transfection of mitochondria and chloroplast DNA in living cells. More particularly, the present invention is based on the use of viral vectors that specifically bind to receptors uniquely found on the target organelle. In one embodiment, as shown in FIG. 1, a eukaryotic cell containing an organelle (1) that has been modified to express a viral receptor (2) on the organelle's surface is provided. A viral vector (6) comprising a desired recombinant DNA construct (3) is introduced into the cytosol of the cell, wherein the viral vector binds to its receptor and introduces the recombinant DNA into the interior of the organelle.

Abstract: The present invention relates to prevention and treatment of strokes and ischemic diseases and to post-ischemic therapeutic treatment. The invention furthermore relates to the use of a growth factor or nucleic acids ensuring increased expression of a growth factor for treating, more particularly restoring the function of ischemic tissue, in particular muscles such as myocardium and skeletal muscles.

Abstract: The present invention relates to a novel use of an ?1G T-type calcium channel transgenic mouse as a nervous disease model, more particularly, a novel use of a mouse deficient in ?1G T-type calcium channel showing novelty-seeking and alcohol preference as a nervous disease model for human nervous related diseases such as novelty-seeking character, alcoholism, anxiety and emotion disorder by stress, etc. The ?1G T-type channel transgenic mice showing novelty-seeking and alcohol preference of the present invention can be effectively used for the development of a medicine and a therapeutic method for human nervous diseases.

Abstract: Described herein are methods and compositions comprising Wnt5a for the diagnosis and treatment of hematopoietic cancers, and methods of identifying therapeutic compounds for the treatment of hematopoietic cancers.

Abstract: Provided are animal models of long QT syndrome (LQTS). The animal models are useful, for example, in screening of drugs for adverse effects in subjects with LQTS, in screening candidate therapeutics for the treatment or prevention of LQTS, and in determining gene expression in LQTS.

Abstract: The invention provide methods and compositions for localized delivery of a vector comprising a therapeutic agent to a specific region of the brain that is overstimulated in neurodegenerative diseases. In particular, the invention provides methods and compositions used to deliver an adeno-associated virus vector (AAV) comprising a nucleotide sequence encoding glutamic acid decarboxylase (GAD) to cells in the hippocampus, subthalamic nucleus of the basal ganglia, mesaphilia and thalamus.

Abstract: Compositions and methods are provided for the treatment of cancer.

Abstract: The present invention provides methods and compositions for modulating skin pigmentation.

Abstract: The present invention relates to human Akt3 proteins and polypeptides. The invention also relates to isolated nucleic acids encoding human Akt3, to vectors containing them and to their therapeutic uses, in particular for gene therapy. Expression of Akt3 inhibits cell death associated with hypoxia, apoptosis or necrosis.

Abstract: The invention provide methods and compositions for localized delivery of a vector comprising a therapeutic agent to a specific region of the brain that is overstimulated in neurodegenerative diseases. In particular, the invention provides methods and compositions used to deliver an adeno-associated virus vector (AAV) comprising a nucleotide sequence encoding glutamic acid decarboxylase (GAD) to cells in the subthalmic nucleus of the basal ganglia, mesaphilia and thalamus.

Abstract: A recombinant nucleic acid comprising nucleotides corresponding to a 3.2 kb 3? untranslated region present in mouse calcium calmodulin kinase II alpha subunit-encoding mRNA is provided. An isolated nucleic acid which hybridizes to the 3? untranslated region of mouse calcium calmodulin kinase II alpha subunit-encoding mRNA under conditions comprising two post-hybridization washes of 15 minutes each at 42° C. in 0.2× standard sodium citrate buffer is also provided.

Abstract: A enhanced method for observing tumor progression, angiogenesis and/or metastasis in animal models in real time is described. The invention employs a skin flap over the area to be observed that can be opened and closed reversibly. The invention also permits simultaneous observation of more than one tumor by use of multiple colors.

Abstract: The invention features a tribonectin and a method of tribosupplementation carried out by administering tribonectins directly to an injured or arthritic joint.

Abstract: A transgenic screen and method for screening biological and chemical test substances or molecules for their ability to influence or modulate the production of BDNF in cells, includes a fusion gene having a zebrafish BDNF gene fragment (promoter) and a fluorescent marker gene inserted downstream of the BDNF gene fragment. When the fusion gene is injected into a zebrafish embryo, the BDNF promoter causes the production of fluorescent protein in various cell types. The embryo is exposed to a test substance for determining the effect thereof on the production of the fluorescent marker protein.

Abstract: Methods for testing candidate drugs for treatment of age-related macular degeneration are provided. Ccl2-deficient, and Ccr2-deficient mice are used to determine the effect of candidate drugs and treatments on development of age-related macular degeneration. Also provided is a Ccl2-deficient, Ccr2-deficient dual knockout mouse, which is a useful animal model for age-related macular degeneration.

Abstract: Disclosed is a cartilage repair product that induces both cell ingrowth into a bioresorbable material and cell differentiation into cartilage tissue. Such a product is useful for regenerating and/or repairing both vascular and avascular cartilage lesions, particularly articular cartilage lesions, and even more particularly mensical tissue lesions, including tears as well as segmental defects. Also disclosed is a method of regenerating and repairing cartilage lesions using such a product.