Abstract: A method of preparing neural precursor cells by exposing pluripotent stem cells or neural stem cells to a differentiation agent. The agent is a pyridine analog, which in preferred embodiments is a phenylethynyl-substituted or phenylazo-substituted pyridine. In other embodiments, a method of enhancing neural precursor cell survival is provided in which the survival is enhanced by exposure to the pyridine analog. In further embodiments, a method of preparing neuronal cells is provided in which pluripotent or neural stem cells exposed to the pyridine analog are then incubated without the pyridine analog, resulting in differentiation into neurons, astrocytes and oligodendrocytes. These methods may be used in toxicological screens, e.g., to evaluate the neurotoxicity of a test compound.

Abstract: The present invention relates to methods of producing germ-like cells (GLCs) from embryonic stem cells and induced pluripotent stem cells, GLCs produced by such methods, gametes derived from such GLCs, pharmaceutical compositions and kits containing such GLCs, screens that use GLCs to identify agents useful in enhancing mammalian reproductive health, and methods of treatment that use GLCs to enhance mammalian reproductive health.

Abstract: The present invention is directed to an isolated population of luminal stem cells obtained from the prostate epithelium that express Nkx3.1. The invention is also directed to methods for diagnosing whether a patient is at risk of developing prostate cancer.

Abstract: A novel growing method is provided for pluripotent stem cells such as ES cells. The method of the invention is a pluripotent stem cell growing method and gene transfer method in which pluripotent stem cells are cultured under conditions that maintain their undifferentiated state and pluripotency, the method being characterized by using a liquid medium and a culturing vessel having immobilized or coated on a substrate solid phase surface a molecule which is adhesive to the pluripotent stem cells in a fixed concentration, to grow the pluripotent stem cells in a dispersed state while maintaining their undifferentiated state and pluripotency, without using feeder cells, or to transfer and express a gene therein.

Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.

Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.

Abstract: The present invention relates to 4,5-bis(4-methoxyphenyl)imidazole compound inducing differentiation of myoblasts or muscle fibers into neuron cells, a pharmaceutical composition including said compound, a method of inducing neuron cells differentiation and a screening method for identifying additional compound useful for inducing neuron cells differentiation. More specifically, it relates to 2-{2-[5-(3-chlorophenyl)]furanyl}-4,5-bis(4-methoxyphenyl)imidazole that induces differentiation of myoblasts or muscle fibers into neuron cells, all pharmaceutically acceptable isomers, salts, and a pharmaceutical composition including said compound, a method of inducing neuron cells differentiation and a screening method for identifying additional compound useful for inducing neuron cells differentiation.

Abstract: Genetically modified mammalian cells comprising a Tol2 transposon transferred into a chromosome can be obtained by co-transfecting mammalian cells with a Tol2 transposase encoded by a Tol2 transposon found in medaka fish, and a Tol2 transposon lacking this transposase.

Abstract: This invention relates to a mammalian artificial chromosome vector, which retains a human chromosome 7 fragment comprising human cytochrome P450 genes and is transmittable to progeny, wherein the human chromosome 7 fragment retains a region of approximately 1 Mb±500 Kb in size comprising at least a human CYP3A gene cluster, which region is located between chromosome markers AC004922 and AC073842, and to a non-human mammalian animal retaining the vector.

Abstract: A trifusion reporter plasmid is described that comprises a plasmid operably coupled to a mammalian FGF1B promoter that is operably coupled to a bioluminescence gene fused to a fluorescence gene fused to a nuclear medical imaging gene. The new reporter allows in vivo or ex vivo detection of gene expression in three different ways, in addition to traditional in vitro detection methods. Transgenic animals containing this new trifusion reporter and uses of same are described.

Abstract: Nucleic acids encoding mammalian, e.g., primate or rodent receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are provided.

Abstract: Problem: An object of the present invention is to quantitate with good accuracy, furthermore, quantitate absolutely, one or a plurality of biological molecules in a sample such as a tissue, a biological fluid, a cell, a cell organ or protein complex. Solution: By adding a metabolically isotope labeled biological molecule as an internal standard substance and measuring with a mass spectrometer, quantitating with good accuracy one or a plurality of target molecules in a sample has become possible. In addition, by performing waveform separation processing during mass analysis, a highly accurate quantitative analysis method of mass analysis is provided.

Abstract: The present invention is directed to a method for the in vitro preparation of cardiovascular progenitors cells from mammalian embryonic stem cells (ES cells) or mammalian embryonic-like state cells, preferably from primate, wherein said method comprises the use of the CD15 (SSEAI) marker as a positive cardiovascular progenitors differentiation marker. The present invention also claimed the use of a receptor tyrosine kinase inhibitor, particularly the SU5402 or SU11248 in association with the BMP2 for improving the efficiency of the desired differentiation. The present invention is also directed to the use of platelet lysate as foetal animal serum substitute in a culture medium intended to the proliferation or propagation of primate ES cells maintaining their pluripotency feature. Derived compositions or kits in relation with the claimed methods or product obtainable by the claimed methods form also part of the present invention.

Abstract: We disclose a method comprising: (a) providing an embryonic stem (ES) cell; and (b) establishing a progenitor cell line from the embryonic stem cell; in which the progenitor cell line is selected based on its ability to self-renew. Preferably, the method selects against somatic cells based on their inability to self-renew. Preferably, the progenitor cell line is derived or established in the absence of co-culture, preferably in the absence of feeder cells, which preferably selects against embryonic stem cells. Optionally, the method comprises (d) deriving a differentiated cell from the progenitor cell line.

Abstract: The present invention relates to systems and methods for maturation, proliferation and maintenance of function in cells presenting hepatocyte characteristics and differentiated from stem cells. The cells of the present invention may be generated from stem cell grown in collagen sandwich configuration in the presence of a morphogen (e.g. S-NitrosoAcetylPenicillamine (SNAP) or Oncostatin-M (OSM)).

Abstract: There is provided an improved efficient method for differentiating stem cells into pancreatic endoderm cells and pancreatic hormone expressing and secreting cells which express Pdx-1 and C-peptide. The invention further provides screening methods for detecting factors of interest that will affect the differentiation of the stem cells into pancreatic endoderm cells.

Abstract: Expression of reprogramming factors such as Sox2, klf4, c-myc, Nanog, LIN28 and Oct4 followed by culture in a MEK inhibitor and a GSK3 inhibitor reprograms tissue cells. The invention provides new uses of these inhibitors, for example in inducing completion of the transcriptional resetting of so-called pre-pluripotent (pre-iPS) stem cells, for example as obtained from mammalian neural stem cells or epiblast stem cells treated with single or combinations of the reprogramming factors, expressed transiently or by integrative vectors. Also provided are systems for reprogramming an epiplast stem cells independently of the use of there inhibitors.

Abstract: The invention relates to the generation of mouse models of drug metabolism in which clusters of genes that are involved in drug metabolism have been knocked out. The development of new drugs and chemicals for therapeutic use or for other purposes is extremely complex. Of particular importance is the understanding of how these chemical agents are handled in the body, whether they have appropriate pharmacokinetics and whether, as a consequence of metabolism, any safety issues arise. Many of the proteins that are involved in the metabolism, disposition and elimination of drugs are members of multigene families that exhibit very marked species differences in gene number, function and regulation. For these reasons, experiments carried out in laboratory animals to establish routes of metabolism or toxicity can be severely compromised and, as a consequence, do not faithfully represent the human situation.

Abstract: Methods and cell lines for overexpressing functional gamma-carboxylated proteins are disclosed by way of genetically engineered cell lines which over-express VKORC1. Also disclosed is the antisense inhibition of expression of calumenin in conjunction with overexpression of VKORC1 which also increases expression of functional gamma-carboxylated proteins. Gamma-carboxylated proteins of interest may include blood coagulation factors such as human clotting factors IX and VII.

Abstract: It is an object of the present invention to provide a non-human gene-disrupted animal with a disrupted ADAM11 gene. According to the present invention, a non-human gene-disrupted animal, wherein either one of or both alleles of an ADAM11 gene are disrupted, is provided.

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 invention provides compositions (e.g., pharmaceuticals, formulations) and methods for ameliorating (e.g., preventing or treating) an anemia and/or stimulating erythropoiesis and/or EPO erythropoietin synthesis. The invention provides compositions comprising a chimeric protein artificial transcription factor comprising a plurality of (multiple) protein DNA-binding domains, e.g., zinc finger binding domains, specific for the promoter region of an erythropoietin (EPO) gene; a consensus nuclear localization protein sequence; a cell-penetrating peptide sequence; and a transcription activation domain.

Abstract: The present invention embraces compositions and methods for establishing and maintaining stem cells and inhibiting stem cell differentiation using a selective Protein Kinase C (PKC) inhibitor.

Abstract: Non-human animal models for frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) are disclosed. The invention relates to a transgenic mouse whose genome comprises a transgene operably linked to a neuronal specific promoter effective for an increased expression of the transgene in the brain of the mouse, in which the transgene comprises a nucleotide sequence encoding TAR DNA-binding protein 43 (TDP-43). The transgenic mouse exhibits reduced or impaired learning and memory capacity, and may further exhibits progressively impaired or reduced motor functions. Methods of using such animal models are also disclosed.

Abstract: It is intended to provide a method for noninvasively isolating human renal stem/progenitor cells, an isolated renal stem/progenitor cells, a therapeutic agent for renal disease, mouse mesenchymal cells which can be used for isolating human renal stem/progenitor cells and a culture supernatant of the same. Renal stem/progenitor cells are isolated by primarily culturing cells contained in the urine of a patient having renal disease in a medium containing mouse mesenchymal cells identified by the deposition number of FERM ABP-10865 or a culture supernatant of the same, staining the obtained primarily cultured cells with Hoechst 33342 and separating a weak-positive or negative fraction.

Abstract: The invention provides for a method for aggregating dermal papilla cells or dermal sheath cells or a combination thereof, the method comprising: growing dermal papilla cells or dermal sheath cells or a combination thereof in suspension culture; and contacting the culture with an effective amount of an enzyme, wherein a substrate of the enzyme is an extracellular matrix molecule in the suspension culture, so as to aggregate dermal papilla cells or dermal sheath cells. The culture may be a hanging drop culture and the enzyme may be a hyaluronidase.

Abstract: The invention is the production of magnetosome-like structures in cells. The invention provides in vitro and in vivo diagnostic and therapeutic methods using eukaryotic cells expressing magnetosome-like structures that act as contrast agents.

Abstract: The present invention relates, in general, to a screening method for identifying novel viral proteins with interferon antagonizing function using a transfection-based assay, and the use of such proteins in isolating various types of attenuated viruses for the development of vaccine and pharmaceutical formulations. The invention also relates to the use of viral interferon antagonists in screening assays to identify potential anti-viral agents. The invention further relates to protocols utilizing interferon antagonists, e.g., NS1, to enhance gene therapy or DNA vaccination based on their ability to increase gene expression.

Abstract: The present invention provides isolated stem cells and progenitor cells, including HCN4-expressing CCS progenitor cells, HCN4- and Islet 1-expressing sinoatrial node cells or progenitor cells thereof, and Islet 1-expressing cardiovascular stem cells that do not express HCN4. The invention further provides differentiated cell types derived from the CCS progenitor cells and cardiovascular stem cells of the invention. In addition, the invention provides methods of differentiating the cells of the invention, methods for screening for agents that affect the differentiation of the cells of the invention, methods for evaluating the potential toxicity of drugs using the cells of the invention, cell therapy using the cells of the invention, and methods of treating heart arrhythmia by ablating HCN4-expressing cells.

Abstract: The present invention provides methods for the reduction of endotoxins in a plasmid preparation using a carbohydrate non-ionic detergent with silica chromatography.

Abstract: The present invention relates to a method for producing a preantral follicle-derived embryonic stem cell and a preantral follicle-derived embryonic stem cell. The present method comprises the steps of (a) obtaining a preantral follicle from mammalian ovaries; (b) growing the preantral follicle in vitro; (c) maturing an oocyte in vitro present in the cultured preantral follicle; (d) activating the matured oocyte for parthenogenesis; (e) culturing the activated oocyte to form a blastocyst; and (f) culturing inner cell mass (ICM) cells of the blastocyst to produce the preantral follicle-derived embryonic stem cell.

Abstract: This invention generally relates to methods for the production of antibody producing cells and antibodies in protooncogene expressing animals. The invention also relates to methods for the efficient production of antibodies specific for antigens that are normally subject to immunological constraints such as self tolerance. The invention further relates to the production of antibody producing cells and antibodies without the need for the conventional fusing of antibody producing B cells with a myeloma fusion partner.

Abstract: The invention relates to a vaccine for the treatment of disease caused by Neisseria, the vaccine including one or more immunogenic components for Neisseria serogroups, as well as antibodies to the immunogenic components and methods of preventing and treating Neisseria infections. The immunogens are based on elements of the inner core lipopolysaccharide.

Abstract: The invention is directed to compounds of Formula (I) or salts thereof. The invention is also directed to use of the compounds of formula (I) in the in vitro preservation of living animal cells. The living cells can be isolated cells, such as stem cells, or groups of cells such as tissue or an organ.

Abstract: Methods for obtaining multipotent Apelin receptor-positive lateral plate mesoderm cells, mesenchymal stem cells, and mesangioblasts under serum-free conditions are disclosed.

Abstract: Purified genes encoding proteins from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding these molecules are provided. Methods of using said reagents and diagnostic kits are also provided.

Abstract: Disclosed herein are an ?1/CaV3.1 double knockout mouse or ??/?;Emx1-Cre mouse with enhanced essential tremor and a screening method of therapeutic agents for essential tremor by using the same. The ?1/CaV3.1 double knockout mouse or ?1?/?;Emx1-Cre mouse of the present invention may be usefully used for development of therapeutic agents for essential tremor because the mouse exhibits essential tremor strong and evident enough to be visually confirmed, compared to an ca knockout mouse.

Abstract: Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

Abstract: A vector includes an enhancer region derived from a transcriptional regulatory region of tyrosine hydroxylase gene wherein the enhancer region enhances transcription amount of a downstream gene in response to a test substance, a promoter which is functionally linked to downstream of the enhancer region, and a reporter gene which is functionally linked to downstream of the promoter.

Abstract: The present invention relates to novel sequences of H. contortus and the proteins encoded therein. This invention also relates to immunogenic compositions, methods for their preparation and the diagnostic, prophylactic or therapeutic use of these sequences and the proteins encoded therein.

Abstract: The present invention provides compositions and methods for the detection of the presence, absence, or quantity of a segmented negative strand RNA virus such as an influenza virus. A genetically engineered vertebrate cell comprising an artificial segment comprising a 5? UTR and a 3? UTR of a segmented negative strand RNA virus and an open reading frame of a reporter gene, preferably in an anti-sense orientation, is contacted with a biological specimen suspected of comprising a segmented negative strand virus. Infection of the cell with a segmented negative strand RNA virus results in expression of a polypeptide encoded by the reporter gene. A genetically engineered cell of the invention can also comprise a recombinant DNA encoding the artificial segment. The recombinant DNA can comprise a promoter for RNA Polymerase I for directing transcription of the artificial segment.

Abstract: The invention features a transgenic mouse that expresses human formyl peptide receptor and methods for producing this mouse. The invention also features methods for the measurement of an inflammatory response, particularly that associated with cystic fibrosis. The methods of the invention also feature methods for determining whether a compound inhibits or prevents the recruitment of neutrophils.

Abstract: Disclosed are embryoid bodies having a uniform size of approximately 415 nm and comprising genetically modified embryonic stem cells, and methods of making same. The genetically uniform embryoid bodies can be multiplexed as one embryoid body per well in a multiwell format, and used as a high to medium throughput screen for test agents that affect the development and homeostasis of animals, including humans. The genetic modification of the embryonic stem cells is a promoter-report-selection construct that enables the selection and detection of cells of a particular lineage in the EB, to determine the effects of a test agent.

Abstract: The present invention relates to the discovery, identification and characterization of a receptor protein, referred to herein as T1R3, which is expressed in taste receptor cells and associated with the perception of bitter and sweet taste. The invention encompasses transgenic animals and cells that do not express functional T1R3 protein, particularly knock-out animals and cells, and transgenic animals and cells that express a non-native T1R3 protein. Experimental model systems based on these animals and cells can be used to study T1R3-mediated taste transduction and responses of the components of the T1R3 signal transduction pathway to various tastants, furthering our understanding of the molecular biology and biochemistry of taste. Such model systems would also be useful for screening for novel tastants and taste modulators, such as enhancers of desirable flavors, and blockers of undesirable flavors.

Abstract: LSD1, a homolog of nuclear amine oxidases, functions as a histone demethylase and transcriptional co-repressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. Lysine demethylation occurs via an oxidation reaction that generates formaldehyde. Importantly, RNAi inhibition of LSD1 causes an increase in H3 lysine 4 methylation and concomitant de-repression of target genes, suggesting that LSD1 represses transcription via histone demethylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases.

Abstract: Methods for screening for modulators of autophagy are disclosed. Methods for identifying genes whose expression inhibits autophagy, as well as genes whose expression promotes autophagy, are disclosed. Also disclosed are methods for identifying compounds that stimulate autophagy, as well as compounds that inhibit autophagy. Cell lines that may be used in the methods of identification are also disclosed.

Abstract: The present invention relates to transgenic non-human animals, tissues or cells derived therefrom and methods of producing them. The transgenic non-human animals or tissues or cells derived therefrom provide a system capable of expressing human proteins responsible for drug metabolism in place of the homologous endogenous non-human animal proteins and for the controlled expression of human genes introduced into the animal so that the expression of the human genes is regulated in a manner more closely analogous to that seen in vivo in humans.

Abstract: The present invention provides for methods, compositions, and kits of producing an induced pluripotent stem cell from a mammalian non-pluripotent cell using exogenous transcription factors.

Abstract: The present invention relates to a method for analyzing the prevention and treatment efficacy of a dendritic cell-derived immunotherapeutic for liver cancer using an animal model carrying tumors expressing a human liver cancer-specific antigen, which comprises the steps of: (a) (a1) administering to a normal animal other than human dendritic cells to be analyzed, or (a1) administering to a normal animal other than human a cancer cell line expressing the human liver cancer-specific antigen to induce cancer in the normal animal; (b) (b1) administering to the animal the cancer cell line expressing the human liver cancer-specific antigen to induce cancer in the animal when the step (a1) is performed in the step (a), or (b1) administering to the animal with cancer dendritic cells to be analyzed when the step (a1) is performed in the step (a); and (c) determining the prevention and treatment efficacy of the dendritic cells as immunotherapeutics for liver cancer by measuring the formation or growth of cancer cells o

Abstract: Binding members directed to human Fas (Fas), in particular antibody molecules against human Fas, employing the antibody VH and/or VL domain of the antibody molecule termed F45D9, which may be in IgG1 or IgG4 format. Methods of use in patients, diseases or disorders involving apoptosis, such as Graft-Versus-Host Disease, HIV-infection, Stevens-Johnson syndrome or Toxic epidermal necrolysis, Islet transplantation as treatment for insulin-dependent diabetes, diseases based on ischemia or ischemic reperfusion injury, heart disease, renal disease, neurological disorders and injuries and lymphocyte depletion in cancer patients associated to cytotoxic antineoplastic therapy.