Abstract: The present invention provides an optimized FLP site-specific recombinase coding sequence and methods for its use. This genetically engineered FLP gene displays a marked increase in recombination efficiency compared to the native FLP gene and is therefore useful in a wide array of molecular applications.

Abstract: Compositions and methods are provided which improve the growth rate, self-renewal potential and capacity of germ line transmission of mouse embryonic stem cells.

Abstract: The invention relates to the isolation and use of hematopoietic and embryonic stem cells. Additionally, the inventors identified the peritoneal cavity as a new source of hematopoietic stem cells. In one embodiment, the invention provides methods of isolating progenitor and/or stem cells from the peritoneal cavity. In another embodiment, the invention provides methods of transporting progenitor and/or stem cells from the peritoneal cavity to another organ. In another embodiment, the present invention provides methods of regenerating bioengineered tissues and/or reconstituting an hematopoietic system.

Abstract: Pluripotent cells are maintained in a self-renewing state in serum-free culture medium comprising a MEK inhibitor, a GSK3 inhibitor and, optionally, an antagonist of an FGF receptor. Pluripotent cells are also maintained in a self-renewing state in serum-free culture medium comprising a MEK inhibitor and an antagonist of an FGF receptor.

Abstract: Animal model involving transgenic manipulation of amyloid precursor protein, useful for testing potential therapeutic agents for the treatment of neurodegenerative disorders, in particular Alzheimer's disease.

Abstract: The present invention relates to transgenic mice and isolated transgenic mouse cells, the mice and mouse cells comprising a disrupted H2 class I gene, a disrupted H2 class II gene, a functional HLA class I transgene, and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cells are deficient for both H2 class I and class II molecules, wherein the transgenic mouse comprises a functional HLA class I transgene and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cell has the genotype HLA-A2+HLA-DR1+?2m°IA?°. The invention also relates to methods of using a transgenic mouse of the invention.

Abstract: The invention provides neuron-derived cells obtained by transfecting a receptor-expressing nucleic acid having an aryl hydrocarbon receptor gene, wherein outgrowth of neurites is not observed without adding a substance for the aryl hydrocarbon receptor, and outgrowth of neurites is observed by adding the substance for the aryl hydrocarbon receptor. The invention also provides a method for determining the presence of neurotoxicity of a test substance, a method for acquiring a marker for determining the presence of neurotoxicity of the test substance, a method for acquiring a marker for neurological dysfunction, and a method for determining the effect of the test substance on neurological dysfunction using such cells.

Abstract: The present application describes a method of producing embryonic stem cell (ESC)-like cells derived from adult mammalian testis. Furthermore, the application describes to a method of producing embryoid bodies from ESC-like cells as well as a method of producing a tissue and/or a differentiated cell from the ESC-like cell or the embryoid body. In addition, an ESC-like cell, an embryoid body and/or differentiated cell and/or tissue obtainable by said methods and pharmaceutical preparations containing the same are provided. Finally, the application describes to the use of these products for medical treatments and the preparation of pharmaceutical compositions for medical treatments.

Abstract: The invention is used as an additive to a culture medium to maintain and grow various cells including stem cells and support their manufactured and secreted products including cytokines, chemokines and growth factors in an environment which provides: a) metabolic enabling or enhancement of measurable parameters within the cellular population b) availability and usage of nutrients to cells c) distinct and positive effect on cellular dynamics (i.e. cellular proliferation and secretion of manufactured products by the cells) d) stabilized environment for maintaining conditions for growth and other cellular and metabolic processes including secretion of manufactured products including signaling factors e) enhanced biological cellular function of inherent cellular processes f) non-interference with normal cellular metabolics (i.e. signaling) g) increased protection from toxic effects to the cell h) additional benefits to the cellular population which in absence of the additive would be lacking.

Abstract: A method of pulsing cultured hepatocytes, such as sandwich-cultured hepatocytes. The method includes providing a culture of hepatocytes, the culture having at least one bile canaliculus; exposing the culture of hepatocytes to a calcium-free buffer, whereby the contents of the at least one bile canaliculus are released; and removing the calcium-free buffer Pulsing cultured hepatocytes can reduce cholestasis arid can provide an in vitro culture of hepatocytes the more closely reflects in vivo hepatocyte characteristics.

Abstract: The present invention relates to novel selection marker vectors, and methods for using these vectors to generate stable gene expression systems in eukaryotic cells utilizing any enzyme useful in the eukaryotic sterol/cholesterol biosynthetic pathway, such as a 3-ketosteroid reductase, as a metabolic selection marker to select transfected cells. In one embodiment, the method comprises transfecting cells that are auxotrophic for cholesterol with a vector encoding 3-ketosteroid reductase and at least one heterologous protein, and selecting cells that have the ability to survive in medium lacking cholesterol and/or producing the heterologous protein in these cells in chemically defined and/or serum-free media.

Abstract: The invention concerns the use of cells capable of carrying out a process of prenylation of proteins coded by the hepatitis C virus (HCV) genome, such as prenylation of the NS5A protein, for replicating and, if required, the production of HCV or derivative viable mutants, in a suitable culture medium.

Abstract: The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate unnatural amino acids into proteins in mammalian host cells, for example, primate host cells and rodent host cells. The invention provides, for example but not limited to, translation systems that include host cells (e.g., primate or rodent cells), orthogonal aminoacyl-tRNA synthetases derived from eubacterial synthetases, orthogonal tRNAs, and the unnatural amino acid. The invention also relates to methods for producing proteins of interest comprising at least one unnatural amino acid in mammalian host cell systems.

Abstract: The present invention provides compounds, compositions and methods for dedifferentiating lineage committed mammalian cells into stem cells. The present invention also provides methods of inducing dedifferentiation of lineage committed mammalian cells into stem cells, which can be further differentiated into various lineage committed cells. Methods of identifying additional compounds useful for inducing dedifferentiation of lineage committed cells into stem cells are also provided.

Abstract: The present invention discloses methods of producing neuronal cells from stem cells, particularly from adult brain stem cells. The use of such neuronal cells in the treatment and/or prevention of neurological diseases, conditions and/or injuries is also disclosed. In addition, the present invention provides a novel source of neuronal cells for use as a laboratory tool.

Abstract: An animal model for HCV replication and/or production of virus or virus like particles is provided. The invention utilizes an HCV replicon present in a cell to deliver HCV nucleic acid and replicate and express HCV proteins in an animal model comprising an animal that has been immunocompromised. The invention further provides a method of treatment or prevention of HCV in a mammal which comprises administering to the mammal a combination which comprises an immunomodulatory compound and another antiviral agent. Also provided are cell lines showing a decreased sensitivity to interferon alpha or some other immunomodulator and methods of making or isolating such cell lines.

Abstract: Methods for obtaining multipotent mesenchymal stem cells under serum-free conditions and methods for identifying multipotent mesenchymal progenitor cells are disclosed.

Abstract: The invention relates to mice which are genetically deprived of T, B lymphocytes and NK cells, deficient for murine MHC class I and/or MHC class II molecules, and transgenic for the expression of the HLA class I and/or HLA class II molecules, and to their use as recipient hosts for the transplantation of human haematopoietic precursors, to study the human adaptative immune system development and function in vivo. The invention relates also to the applications of this human/mouse chimera model to improve immunotherapy against pathogens, cancer and autoimmune diseases.

Abstract: The present invention provides isolated anti-interferon alpha monoclonal antibodies, particularly human monoclonal antibodies, that inhibit the biological activity of multiple interferon (IFN) alpha subtypes but do not substantially inhibit the biological activity of IFN alpha 21 or the biological activity of either IFN beta or IFN omega. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting the biological activity of IFN alpha using the antibodies of the invention, as well as methods of treating disease or disorders mediated by IFN alpha, such as autoimmune diseases, transplant rejection and graft versus host disease, by administering the antibodies of the invention.

Abstract: Disclosed are cells exhibiting neuronal progenitor cell characteristics, and methods of making them from marrow adherent stem cells by regulating cellular pathways in the marrow adherent stem cells that are associated with glial transdifferentiation of the marrow adherent stem cells.

Abstract: The present invention generally relates to gene silencing using sense DNA (sDNA)-antisense RNA (aRNA) hybrids wherein the sense DNA strand is coupled to a peptide which facilitates the uptake of the hybrid into cells.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO69122, PRO204, PRO214, PRO222, PRO234, PRO265, PRO309, PRO332, PRO342, PRO356, PRO540, PRO618, PRO944, PRO994, PRO1079, PRO1110, PRO1122, PRO1138, PRO1190, PRO1272, PRO1286, PRO1295, PRO1309, PRO1316, PRO1383, PRO1384, PRO1431, PRO1434, PRO1475, PRO1481, PRO1568, PRO1573, PRO1599, PRO1604, PRO1605, PRO1693, PRO1753, PRO1755, PRO1777, PRO1788, PRO1864, PRO1925, PRO1926, PRO3566, PRO4330, PRO4423, PRO36935, PRO4977, PRO4979, PRO4980, PRO4981, PRO5801, PRO5995, PRO6001, PRO6095, PRO6182, PRO7170, PRO7171, PRO7436, PRO9912, PRO9917, PRO37337, PRO37496, PRO19646, PRO21718, PRO19820, PRO21201, PRO20026, PRO20110, PRO23203 or PRO35250 genes.

Abstract: The current invention describes a nucleic acid comprising in a 5? to 3? direction a) a first nucleic acid encoding a heterologous polypeptide without an in frame stop codon, b) a second nucleic acid beginning with a 5? splice donor site and terminated by a 3? splice acceptor site comprising an in frame translational stop codon and a polyadenylation signal, and c) a nucleic acid encoding i) at least a fragment of a transmembrane domain, or ii) a signal peptide for a GPI-anchor.

Abstract: Mechanisms regulating cell proliferation stop and differentiation initiation during the development stage of mammalian embryo, and the proteins involved therein, are presented. Differentiation regulators, methods of regulating differentiation, transgenic organisms with loss of expression of the differentiation regulator, and methods of preparing the transgenic organisms, are provided.

Abstract: The present invention provides a transgenic mouse retaining a DNA that encodes an exogenous GPR40 in an expressible state, wherein (1) the insulin secretion capacity has been increased, and/or (2) the glucose tolerance has been improved, compared with the corresponding non-transgenic mouse, or a portion of the living body thereof, a screening method for a prophylactic/therapeutic drug for diabetes mellitus and metabolic syndrome using the transgenic mouse, and the like.

Abstract: The invention relates to genetic elements capable of improving the levels of expression of operably-linked transcription units. In particular, said genetic elements are derived from the 5? untranslated regions of ribosomal protein genes and may comprise a CpG island. Also provided are vectors and host cells comprising said genetic elements and methods of use to obtain high levels of recombinant gene expression.

Abstract: Described herein are methods of generating a genetically modified cell by providing a zinc finger endonuclease (ZFE) that includes an endonuclease domain that cuts DNA, and a zinc finger domain that includes a plurality of zinc fingers that bind to a specific nucleotide sequence within the endogenous chromosomal target DNA in the primary cell. Further, the methods can include contacting the endogenous chromosomal target DNA sequence with the zinc finger endonuclease in the primary cell such that the zinc finger endonuclease cuts both strands of a nucleotide sequence within the endogenous chromosomal target DNA sequence in the primary cell, thereby enhancing the frequency of homologous recombination in the endogenous chromosomal target DNA sequence.

Abstract: A method for analyzing the prevention and treatment efficacy of a dendritic cell-derived immunotherapeutic for prostate cancer using an animal model carrying tumors expressing a human prostate cancer-specific antigen includes either administering to a normal non-human animal dendritic cells to be analyzed, or administering to a normal non-human animal a cancer cell line expressing the human prostate cancer-specific antigen to induce cancer in the normal non-human animal; administering to the animal the cancer cell line expressing the human prostate cancer-specific antigen to induce cancer in the animal when the dendritic cell administering step was performed, or administering to the animal with cancer dendritic cells to be analyzed when the human prostate cancer-specific antigen expressing cell line administering step was performed; and determining the prevention and treatment efficacy of the dendritic cells as immunotherapeutics for prostate cancer by measuring the formation or growth of cancer cells origina

Abstract: Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO286, PRO706, PRO1800, PRO4354, PRO6029, PRO9739, PRO20044, PRO28631 or PRO34128 genes. Such in vivo studies and characterizations may provide valuable identification and discovery of therapeutics and/or treatments useful in the prevention, amelioration or correction of diseases or dysfunctions associated with gene disruptions such as neurological disorders; cardiovascular, endothelial or angiogenic disorders; eye abnormalities; immunological disorders; oncological disorders; bone metabolic abnormalities or disorders; lipid metabolic disorders; or developmental abnormalities.

Abstract: An antibody binding to IPC was obtained by using an animal cell in which a cell membrane protein associatable with ILT7 was co-expressed as an immunogen. The antibody of the invention has a high specificity which allows immunological distinction between other ILT family molecules and ILT7. The anti-ILT7 antibody of the invention bound to IPC and inhibited the activity thereof. With the anti-ILT7 antibody of the invention, the IPC activity can be inhibited and an interferon-related disease can be treated or prevented. ILT7 expression is maintained even in IPC in the presence of IFN?. Therefore, an inhibitory action of IPC activity by the anti-ILT7 antibody can be expected even in an autoimmune disease patient with an increased production of IFN?.

Abstract: The invention relates to a method of forming pancreatic hormone-producing endocrine cells in vitro, wherein pancreatic stem cells are treated with one or more retinoids and/or retinoic acid in vitro and cultured. Especially the dorsal pancreatic bud is used and to the cells obtained by the method. Further, it relates to the use of the pancreatic hormone-producing endocrine cells, for the production of a pharmaceutical composition for transplantation and/or treatment of type 1 and type 2 diabetes. It also relates to a method for treatment of type 1 and type 2 diabetes by administrating the hormone-producing endocrine cells to individuals in need thereof. The invention also regards the use of one or more retinoids and/or retinoic acid for the differentiation, in vitro of pancreatic stem cells into pancreatic hormone-producing endocrine cells, such as glucagon producing cells, and in particular, insulin producing ?-cells.

Abstract: Genetically engineered conditional knock-out mice having conditional disruption of the Abi1/Hssh3bp1 gene are disclosed along with methods of making and using same.

Abstract: Genetically modified mice and nucleic acid constructs for making the genetically modified mice are described. A first mouse having a gene encoding an activator (such as a Cre recombinase) operably linked to a developmentally-regulated promoter (such as a Nanog promoter) is provided. A second mouse having a toxic responder gene (such as a gene encoding diphtheria toxin A) is provided, where the toxic gene is expressed only in the presence of an activator, Embryos from a mating of the first and the second mouse are provided as host embryos suitable for generating mice from donor cells introduced into the host embryos. Ablating the ICM of a mouse embryo physically, chemically, or genetically is described, as well as making F0 generation mice that are substantially or in full derived from donor cells, employing a host mouse embryo with an ablated or nonproliferating ICM.

Abstract: The purification and isolation of various genes which encode mammalian cell surface polypeptides. Nucleic acids, proteins, antibodies, and other reagents useful in modulating development of cells, e.g., lymphoid and myeloid, are provided, along with methods for their use.

Abstract: Compositions and methods are provided for screening for compounds that modulate insulin promoter activity. Vectors that express green fluorescent protein under the control of the human insulin promoter are introduced into mouse and human cells in which the insulin promoter is expressed in a glucose-responsive manner. Such cells are then used to screen for compounds that modulate insulin promoter activity.

Abstract: The present invention relates to siRNAs that are targeted to RNAs encoding two or more enzymes of a subfamily of cytochrome P450 (CYP) enzymes, along with vectors, cells, and kits comprising the siRNAs. The invention further relates to methods of decreasing expression of two or more CYP subfamily genes in a non-human animal, animals in which expression of two or more CYP subfamily genes has been decreased, and methods of using such animals to study the function of cytochrome P450 enzymes.

Abstract: The present invention provides methods, media and compositions capable of modulating the differentiation of stem cells. Applicants have discovered that agonists of lysophospholipid receptors and ligands of class III tyrosine kinase receptors are useful in preventing the spontaneous differentiation of stem cells. The ligands and agonists may be used alone, or in combination where they have a synergistic effect. Also provided are cells produced using the methods and media, and methods of treating stem cell related diseases using the compositions described herein. Methods of identifying compounds useful in finding other agents useful in the modulation of stem cell differentiation are also disclosed.

Abstract: The cloning of a fourth mouse SCD gene, mSCD4, as well as its corresponding cDNA and amino acid sequences are disclosed. Mouse SCD4 is expressed mainly in the heart tissue and synthesizes the bulk of monounsaturated fatty acids in the heart. The disclosure here enables new tools (e.g., nucleic acids, polypeptides, antibodies, vectors, recombinant cells, and transgenic and knock-out animals) for studying the function of various SCD isoforms and their connection to various disease conditions. New tools for converting saturated fatty acyl-CoA to monounsaturated acyl-CoA and for identifying SCD modulators including isoform-specific modulators are also enabled. In addition, given that accumulation of lipid in the heart (fatty heart) can have deleterious consequences, the present invention also provides a new prevention and treatment target for fatty heart as well as methods for screening candidate drugs.

Abstract: The invention provides a method of making a pluripotent stem cell from a cell that is not pluripotent, such as from a differentiated stem cell or a lineage-restricted stem cell. The methods comprise culturing the starting cell in the presence of one or more epigenetic altering agents, such as a histone deacetylase inhibitor and/or a DNA methyltransferase inhibitor. Pluripotent stem cells are also provided, as are methods of treating or preventing a disease, disorder, or condition in a mammal using the cells.

Abstract: Nucleic acids encoding a new family of small cysteine rich soluble proteins, from a mammal, reagents related thereto, including specific antibodies, and purified proteins are described. Methods of using said reagents and related diagnostic kits are also provided.

Abstract: Embodiments described herein include nucleic acid sequences, which encode hepatitis C virus of strain HC-TN, genotype 1a, proteins and polypeptides and fragments thereof. Use of these compositions, and diagnostics for HCV and in the development of screening assays for the identification of antiviral agents for HCV are also contemplated.

Abstract: A gene trap vector comprises a DNA construct containing an expression unit of an internal ribosome binding site (IRES) coupled to a heterologous gene sequence; this expression unit is used in gene trap protocols to obtain expression of the heterologous gene in the host.

Abstract: The present invention relates to a non-human mammal in which all cells contain genetic modifications in a Ca2+ handling Serca ATPase gene, more particularly the Serca2 ATPase. Defective Ca2+ handling is induced in live animals by introducing genetic elements which direct the timing and specificity of the gene inactivation to the organ or tissue of interest; e.g. cardiac muscle cells. The primary application is to provide a standardized and reproducible animal model for heart failure or other human diseases, in which the defective Ca2+ handling function by the Serca gene can be manipulated in live animals. This is the only existing animal to date with such genetic modifications for this class of Ca2+ handling proteins.

Abstract: The present invention provides for fully human antibodies and chimeric antibodies that bind human TYRP1 antigen with an affinity comparable to or higher than TA99, a murine antibody specific to TYRP1. The invention further provides polynucleic acids and host cells that encode and express these antibodies. The invention also provides for methods of modulating activity of TYRP1, treating growth of a cancer cell, and treating a malignant melanoma in mammals by administering an effective amount of an antibody either alone or in combination with an anti-cancer agent or treatment.

Abstract: The present invention relates to a cell for the production of an antibody molecule such as an antibody useful for various diseases having high antibody-dependent cell-mediated cytotoxic activity, a fragment of the antibody and a fusion protein having the Fc region of the antibody or the like, a method for producing an antibody composition using the cell, the antibody composition and use thereof.

Abstract: The present invention provides isolated cultures of immortalized retinal pigmented epithelial cells. The cells retain one or more of the in vivo characteristics of non-immortalized retinal pigmented epithelial cells, including, for example, cobblestone morphology, polarization, the presence and/or expression of one or more protein markers, and a metabolic pattern typical of non-immortalized retinal pigmented epithelial cells. The present invention also provides methods of making and using immortalized retinal pigmented epithelial cells.

Abstract: The present invention relates to a nuclear reprogramming factor having an action of reprogramming a differentiated somatic cell to derive an induced pluripotent stem (iPS) cell. The present invention also relates to the aforementioned iPS cells, methods of generating and maintaining iPS cells, and methods of using iPS cells, including screening and testing methods as well as methods of stem cell therapy. The present invention also relates to somatic cells derived by inducing differentiation of the aforementioned iPS cells.

Abstract: The presently disclosed subject matter provides populations of stem cells that are purified from bone marrow, peripheral blood, and/or other sources. Also provided are methods of using the stem cells for treating tissue and/or organ damage in a subject.

Abstract: The invention provides, among other things, methods for performing RNA interference (RNAi) in stem cells (such as embryonic stem cells) and methods for using such stem cells in vivo. The invention also provides various animal models based on conditional/inducible, reversible, tissue-specific/spacial, and/or developmental stage-specific/temporal RNAi of certain target genes, which animal model may be useful for, e.g., drug target identification and/or validation.