Abstract: The present invention provides a human artificial chromosome vector comprising a gene encoding the human antibody heavy chain, a gene encoding the human antibody light chain, and a gene encoding IgM heavy chain constant region derived from a nonhuman animal; and being capable of producing a human antibody with a higher efficiency when the vector is introduced into an animal. By immunizing the animal produced using a human artificial chromosome vector of the present invention with a desired antigen, a large quantity of human polyclonal antibodies can be supplied.

Abstract: The invention features methods of treatment and diagnosis using NRG-2 polypeptides, nucleic acid molecules, and antibodies. The invention also provides novel NRG-2 polypeptides and nucleic acid molecules.

Abstract: Methods of increasing production, stability or activity of a target polypeptide are provided herein. The method includes increasing the level of an antioxidant in a cell comprising a polynucleotide encoding the target polypeptide. Also provided are cells and transgenic organisms produced using the methods described herein. Methods of treating a subject with a condition treatable by administration of the target polypeptide are also disclosed. Finally methods and compositions for transiently increasing antioxidants in plant cells are provided.

Abstract: The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

Abstract: This invention features methods and compositions useful for treating and diagnosing diseases of the nervous system, retina, skin, muscle, joint, and cartilage using a Dragon family protein. Protein and nucleic acid sequences of human, murine, zebrafish, and C. elegans Dragon family members are also disclosed.

Abstract: Nucleic acid compositions encoding non-aggregating chromo/fluoroproteins and mutants thereof, as well as the proteins encoded by the same, are provided. The proteins of interest are polypeptides that are non-aggregating colored and/or fluorescent proteins, where the non-aggregating feature arises from the modulation of residues in the N-terminus of the protein and the chromo and/or fluorescent feature arises from the interaction of two or more residues of the protein. Also provided are fragments of the subject nucleic acids and the peptides encoded thereby, as well as antibodies to the subject proteins and transgenic cells and organisms. The subject protein and nucleic acid compositions find use in a variety of different applications. Finally, kits for use in such applications, e.g., that include the subject nucleic acid compositions, are provided.

Abstract: This invention features methods and compositions useful for treating and diagnosing diseases of the nervous system, retina, skin, muscle, joint, and cartilage using a Dragon family protein. Protein and nucleic acid sequences of human, murine, zebrafish, and C. elegans Dragon family members are also disclosed.

Abstract: A myeloid-specific c-fms-rtTA/(TetO)7-CMV-MMP12 bitransgenic mouse model was created. Induction of MMP12 abnormally elevated frequencies and numbers of common myeloid progenitor (CMP) and granulocyte/macrophage progenitor (GMP) populations, and decreased the frequency and number of the megakaryocyte/erythrocyte progenitor (MEP) population in bone marrow. CD11b+/Gr-1+ immature cell population increased in multiple organs. An immunosuppressive function on T cell proliferation and function by CD11b+/Gr-1+ immature cells was seen in vitro and in vivo from MMP12 over-expression. MMP12 stimulated (Lin?) progenitor cells to differentiate into CD11b+/Gr-1+ immature cells showing immunosuppression on T cell proliferation and function in vitro. Regulatory T cells were increased. In the lung, concentration of interleukin (IL)-6 was increased, which activated oncogenic signal transducer and increased expression of Stat3 downstream genes in epithelial tumor progenitor cells.

Abstract: The present invention relates to an assay for detecting virus, in particular an assay for detecting viral replication in a tissue sample. The invention also relates to methods of determining the susceptibility of an animal to a virus, and methods of breeding animals with decreased susceptibility to a virus.

Abstract: The present invention provides compositions and methods for studying neuropathy. The compositions and methods provided herein are particularly useful for screening agents of therapeutic and/or diagnostic potential.

Abstract: The present invention relates to transgenic blue ornamental fish, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic fish and methods of providing them to the ornamental fish industry for the purpose of marketing.

Abstract: It is an object to provide a gene-modified non-human animal having inactivated MGAT2 gene and a gene-modified non-human animal cell, which are useful for the search of the function of MGAT2 in vivo. It is another object to provide a method for screening of a compound capable of inhibiting the activity of MGAT2 and a compound capable of inhibiting the activity of MGAT2. It is further another object to provide a method for detecting a disease induced by abnormal lipid metabolism based on the expression level or activity of MGAT2. A method for screening of a compound by using a gene-modified non-human mammal having the artificially inhibited expression of MGAT2 gene and a cell thereof enable to prevent or treat a disease induced by abnormal lipid metabolism. Also a screening of a compound capable of inhibiting or enhancing the function of MGAT2 enables to prevent or treat a disease induced by abnormal lipid metabolism.

Abstract: The present invention relates to the method and use of fluorescent proteins in making purple transgenic fluorescent fish. Also disclosed are methods of establishing a population of such transgenic fish and methods of providing them to the ornamental fish industry for the purpose of marketing. Thus, new varieties of ornamental fish of different fluorescence colors from a novel source are developed.

Abstract: The present invention concerns the preparation of substantially purified agonist anti-EDAR monoclonal antibodies or isolated monoclonal antibody fragments or antigen binding portions or fragments thereof. The invention further relates to isolated agonist anti-EDAR monoclonal antibodies or isolated monoclonal antibody fragments or antigen binding portions or fragments thereof as well as their use in the treatment of X-linked hypohidrotic ectodermal dysplasia and tooth agenesis. The invention also relates to a pharmaceutical composition comprising said isolated agonist anti-EDAR monoclonal antibodies or isolated monoclonal antibody fragments or antigen binding portions or fragments thereof and to a method of treating X-linked hypohidrotic ectodermal dysplasia and tooth agenesis. Finally, the present invention concerns a pharmaceutical kit comprising said isolated agonist anti-EDAR monoclonal antibodies or isolated monoclonal antibody fragments or antigen binding portions or fragments thereof.

Abstract: With an aim to provide means for developing a compound devoid of teratogenicity but retaining beneficial actions, a screening method for a non-teratogenic substance comprising bringing a test substance into contact with cereblon or a fragment of cereblon, evaluating the bindability of the test substance with cereblon or the fragment of cereblon, and selecting a test substance that does not bind to cereblon or the fragment of cereblon or a test substance exhibiting lower bindability with cereblon or the fragment of cereblon than does thalidomide is provided.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: The present invention relates to a recombinant organism having any one of nucleic acids (i) to (iv) introduced therein: (i) a nucleic acid having a base sequence of SEQ ID NO: 1; (ii) a nucleic acid encoding a protein having an amino acid sequence of SEQ ID NO: 2; (iii) a nucleic acid encoding a dragline protein and having a sequence identity of 90% or more with the nucleic acid (i); (iv) a nucleic acid which encodes a dragline protein and hybridizes with a complementary chain of the nucleic acid (i) under stringent conditions.

Abstract: The instant invention relates to the use of 24-hydroxylated vitamin D compounds as therapeutics in mammalian bone fracture repair. In addition, the instant invention relates to novel 24-hydroxylated vitamin D compound receptors which can be employed in the development of compounds capable of facilitating fracture repair in animals. The instant invention also relates to nucleic acids encoding such receptors as well as vectors, host cells, transgenic animals comprising such nucleic acids and screening assays employing such receptors.

Abstract: The present invention provides a genetically-modified non-human animal whose somatic and germ cells contain an exogenous gene encoding a recombinant fusion protein, wherein the presence, and expression, of said recombinant fusion protein renders said genetically-modified non-human animal sterile. Tools for generating such sterile genetically-modified non-human animal as well as methods of use thereof are also provided.

Abstract: The present invention relates to the identification of polynucleotides and polypeptides involved in insulin and adiponectin signaling and regulation of glucose production. The invention further relates to the use of the identified polynucleotides and polypeptides, and inhibitors of the polynucleotides and polypeptides, in the regulation of glucose production and the monitoring and treatment of metabolic disorders such as diabetes.

Abstract: An isolated polynucleotide encoding a modified luciferase polypeptide and substrates. The OgLuc variant polypeptide has at least 60% amino acid sequence identity to SEQ ID NO: 1 and at least one amino acid substitution at a position corresponding to an amino acid in SEQ ID NO: 1. The OgLuc variant polypeptide has at least one of enhanced luminescence, enhanced signal stability, and enhanced protein stability relative to the corresponding polypeptide of the wild-type Oplophorus luciferase.

Abstract: An I-CreI variant, wherein at least one of the two 1-Cre1 monomers has at least two substitutions, one in each of the two functional subdomains of the LAGLIDADG core domain situated from positions 26 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from the genome of a non-integrating virus, in particular herpes simplex virus (HSV) or Hepatitis B virus (HBV) for use in genome engineering and for in vivo and ex vivo (gene cell therapy) genome therapy as well as the treatment of a virus infection.

Abstract: The invention relates to the field of longevity enhancement. More particularly, the invention provides compositions and methods relating to CRTC modulation. In certain embodiments, the invention provides compositions and methods for enhancing longevity in an organism by inhibiting CRTC activity, such as, for example, inhibiting CRTC expression or cellular localization in the organism.

Abstract: The present invention provides methods for modulating mitochondrial function, modulating lesion formation in the brain, modulating neurite growth, modulating neuronal degeneration, and treating and preventing neurological diseases or disorders comprising modulating the expression of activity of PGC-1?. The present invention also provides an animal, e.g., transgenic mouse, in which the PGC-1? gene is misexpressed. Methods for identifying compounds which are capable of treating or preventing a neurological disease or disorder are also described.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel ecdysone receptor/invertebrate retinoid X receptor-based inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: Compositions and methods that allow for the rapid detection and accurate quantification of any polypeptides of interest are provided. Compositions include isolated polypeptides comprising at least one universal peptide tag, as well as isolated polynucleotides encoding such polypeptides. The universal peptide tags can be quantified by methods including, but not limited to, mass spectrometry, and can act as surrogates for determining the concentration of the polypeptides comprising the universal peptide tags. Methods provide for the detection and/or quantification of any polypeptides of interest that comprise at least one universal peptide tag, including methods using mass spectroscopy techniques. Methods are also provided for producing hosts, or cells or parts thereof, that comprise polypeptides comprising at least one universal peptide tag. Hosts, or cells, or parts thereof, include mammalian, bacterial, insect, yeast, viral or plant.

Abstract: Isolated nucleic acid molecules encoding T-bet, and isolated T-bet polypeptides, are provided. The invention further provides antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals carrying a T-bet transgene. The invention further provides T-bet fusion proteins and anti-T-bet antibodies. Methods of using the T-bet compositions of the invention are also disclosed, including methods for detecting T-bet expression and/or activity in a biological sample, methods of modulating T-bet expression and/or activity in a cell, and methods for identifying agents that modulate the expression and/or activity of T-bet.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with MD. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to study MD development and methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with MD.

Abstract: The amino acid and nucleic acid sequences of a ?5-desaturase enzyme and a ?8-desaturase enzyme are disclosed. The nucleic acid sequences can be used to design recombinant DNA constructs and vectors. These vectors can then be used to transform various organisms, including for example, plants and yeast. The transformed organisms will then produce polyunsaturated fatty acids. The amino acid sequences are useful for generating enzyme-specific antibodies that are useful for identifying the desaturases.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences involved in ADME and toxicology. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. The invention also provides zinc finger nucleases that target chromosomal sequence involved in ADME and toxicology and the nucleic acids encoding said zinc finger nucleases. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences involved in ADME and toxicology.

Abstract: New rare-cutting endonucleases, also called custom-made meganucleases, which recognize and cleave a specific nucleotide sequence, derived polynucleotide sequences, recombinant vector cell, animal, or plant comprising said polynucleotide sequences, process for producing said rare-cutting endonucleases and any use thereof, more particularly, for genetic engineering, antiviral therapy and gene therapy.

Abstract: The present invention provides a high affinity, antigen-specific, soluble heavy chain-only antibody which: lacks hallmark camelid-related amino acid substitutions and has FR2 substitutions which are not found in antibodies which comprise heavy and light chain; shows increased net hydrophobicity within CDR1 and an increased number of charged amino acids present in CDR3; and comprises one or more amino acid substitutions within the framework ?-pleated sheet leading to increased net hydrophobicity within FR1 and an increased number of charged amino acids present in FR3. Also provided are VII domains having the same properties, gene segments for their production, methods for their production, transgenic animals and uses of the antibody of the VH domains in therapy.

Abstract: In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucleotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly contiguous heavy and light chain sequences spanning the complementarity determining regions (CDRs), specifically from within FR1 and/or CDR1 through CDR3 and/or within FR4, are provided. Further provided are antibodies having similar binding properties and antibodies (or other antagonists) having similar functionality as antibodies disclosed herein.

Abstract: The invention relates to muteins of the pyrroline-5-carboxylate reductase 1 (PYCR1), to nucleic acid molecules comprising a nucleotide sequence encoding such muteins, to methods of determining in a subject a predisposition of having an age related disorder associated with PYCR1, to methods of identifying a compound capable of modifying the expression of PYCR1 and methods of treating a subject having an age-related disorder associated with PYCR1. The invention further relates to a genetically modified animal and a method of modifying the expression of the PYCR1 gene in an animal.

Abstract: The present application relates to apoptotic anti-IgE antibodies, nucleic acid encoding the same, therapeutic compositions thereof, and their use in the treatment of IgE-mediated disorders.

Abstract: The invention relates to nematodes as model organisms for the investigation of neurodegenerative diseases, in particular, Parkinsons disease, uses and methods for the discovery of substances and genes which can be used in the treatment of the above disease states and identification of a nematode gene, From C elegans, which is homologous to the human parkin gene associated with Parkinsons disease. The invention further relates to those nematodes which contain an aberrant or missing expression of at least one gene, preferably a parkin gene and/or a ?-synucleine gene, which is connected with Parkinsons disease. According to the invention, the above organisms can be used for the identification and characterization of medicaments for the treatment of said disease states.

Abstract: The present invention provides an agent that modulates physiological condition of pests, wherein the agent has an ability to modulate the activity of an insect voltage-gated potassium channel; a method for assaying pesticidal activity of a test substance, which comprises measuring the activity of a voltage-gated potassium channel in a reaction system in which the voltage-gated potassium channel contacts with a test substance, and so on.

Abstract: The present invention relates, in general, to siRNA and, in particular, to a method of effecting targeted delivery of siRNAs and to compounds suitable for use in such a method.

Abstract: The present invention provides compositions, methods, and kits for generating and isolating tagged nuclei of specific cell types with a high yield and purity. The compositions, methods, and kits provided herein comprise expressing in a cell a nuclear envelope tagging fusion polypeptide comprising a nuclear envelope targeting domain and an affinity reagent binding region. In some embodiments, expression of the fusion polypeptide is under the control of a cell type-specific promoter. Some embodiments also comprise expressing in a cell a biotin ligase, wherein the affinity reagent binding region comprises a biotin ligase accepting site, and wherein at least one of the nuclear envelope tagging fusion polypeptide and the biotin ligase is expressed under the control of a cell type-specific promoter.

Abstract: The present invention relates to a method for producing transformed earthworms using the gonad-regenerating capability of earthworms, to transformed earthworms produced by the method, and to a method for producing recombinant proteins from the body fluids of transformed earthworms. The method for producing transformed earthworms according to the present invention is a novel biotechnology technique which overcomes the drawbacks of conventional transgenesis techniques, and which has high injection efficiency. The method for producing transformed earthworms according to the present invention uses regenerative blast cells having totipotency, such as embryonic stem cells, and therefore, recombinant genes can be incorporated throughout the entire transformant, and recombinant proteins can be made from the body fluids of the transformant.

Abstract: The invention provides a modified version of alpha B-Crystallin (?BC), and methods for delivering this modified version of alpha B-Crystallin (?BC) to tissues and cells; the invention provides a modified version of ?BC in which the serine at position 59 has been changed to glutamate to mimic phosphorylation and the serine at positions 19 and 45 have been changed to alanine to prevent phosphorylation of those residues. The invention also provides compositions and methods for ameliorating a cell from ischemia/reperfusion injury or protecting a cell from ischemia/reperfusion injury.

Abstract: The present invention relates to a method to engineer either the genome of a genetically modified organism, other bioengineered reagent, or in vitro translation system for protein synthesis from specific protein-coding genes so that the protein-coding genes so engineered can only produce proteins with an intended structure when translated within the context of that specifically engineered GMO or in vitro translation system. It also relates to nucleic acids for use in such GMOs or translation systems.

Abstract: The present invention refers to monoclonal humanized antibodies, which bind to the extracellular domain of the AXL receptor tyrosine kinase and which at least partially inhibit AXL activity.

Abstract: The invention relates to Citrobacter phytases derived from Citrobacter amalonaticus, Citrobacter gillenii, and related phytases. The phytases belong to the acid histidine phosphatase family, are acid-stable, and expectedly of a high specific activity. The invention also relates to the corresponding DNA, the recombinant and wild-type production of the phytases, as well as the use thereof, in particular in animal feed.

Abstract: An epilepsy model animal (CHRNA4:S284L) developing spontaneous epileptic seizure during sleep, which is a nonhuman animal established by ontogenesis of a totipotent cell into which a polynucleotide encoding nonhuman mutant CHRNA4 is introduced and having said polynucleotide in its somatic chromosome, or a progeny of the nonhuman animal, wherein said nonhuman mutant CHRNA4 has the corresponding mutation of human mutant CHRNA4 in which the 284th Ser of SEQ ID NO: 1 is substituted by Leu. The epilepsy model animal has gene abnormality homologous to human chromosomal dominant nocturnal frontal lobe epilepsy and a symptom (epileptic seizure during sleep) the same as that of human autosomal dominant nocturnal frontal lobe epilepsy.

Abstract: The present invention refers to methods for selectively recognizing a base pair in a DNA sequence by a polypeptide, to modified polypeptides which specifically recognize one or more base pairs in a DNA sequence and, to DNA which is modified so that it can be specifically recognized by a polypeptide and to uses of the polypeptide and DNA in specific DNA targeting as well as to methods of modulating expression of target genes in a cell.

Abstract: The present invention relates to at least one novel chimeric, humanized or CDR-grafted anti-IL-6 antibodies derived from the murine CLB-8 antibody, including isolated nucleic acids that encode at least one such anti-IL-6 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

Abstract: The present invention refers to human EGLN2 variants having at position 58 of the amino acid sequence a serine or a leucine and their use in the prevention or treatment of thromboembolic or coronary heart diseases, in particular stroke, prolonged reversible ischemic neurological deficit (PRIND), transitoric ischemic attack (TIA), myocardial infarction and/or early myocardial infarction.

Abstract: The present invention relates to polypeptides having phytase activity. These polypeptides have an amino acid sequence which has at least 70% identity to either of three phytases derived from the bacterium Buttiauxella, and which comprises at least one of the following amino acids at the position indicated: 119N, 120L, and/or 121E. These phytases have an improved specific activity. Additional specific amino acid substitutions are also disclosed which characterize and distinguish additional phytases of the invention having improved properties such as temperature and/or pH stability, pH activity profile, temperature activity profile, substrate profile, improved performance in animal feed in vitro or in vivo. The invention also relates to isolated polynucleotides encoding the polypeptides, nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

Abstract: The nucleotide and amino acid sequences of indoleamine 2,3-dioxygenase-2 (IDO2) and methods of use thereof are provided.