Abstract: Monoclonal antibodies which specifically bind human CD23, the low affinity receptor for IgE (FceRII/CD23), and contain either a human gamma-1 or human gamma-3 constant domain, are disclosed. The antibodies are useful for modulating or inhibiting induced IgE expression. Accordingly, they have practical utility in the treatment or prophylaxis of disease conditions wherein inhibition of induced IgE production is therapeutically desirable, including allergic conditions, autoimmune diseases and inflammatory diseases.

Abstract: Methods of preparing a NELL peptide are disclosed.

Abstract: The present invention relates to a method of inducing apoptosis in a tumour cell as well as modulating pluripotency and/or self-renewing characteristics of a stem/progenitor cell. The method comprises administering to the respective cell a compound of general formula (I). In general formula A is C or N. R1, R4 and R5 are, independently selected, H or aliphatic, cycloaliphatic aromatic, arylaliphatic, or arylcycloaliphatic hydrocarbyl groups, that comprise 0-3 heteroatoms being N, O, S, or Si. R4 and R5 may optionally be linked so as to define an aliphatic hydrocarbyl bridge. R2 is H or a halogen, such as F or Cl. R3 is H, or an aliphatic or arylaliphatic hydrocarbyl group comprising 1-8 main chain carbon atoms and 0-3 heteroatoms being N, O, S, Si, or a halogen such as Cl or F. Also provided is a pharmaceutical composition for inducing apoptosis in a tumour cell and/or modulating pluripotency and/or self-renewing characteristics of a stem/progenitor cell.

Abstract: The present inventors discovered that knockout mice whose S1-5 gene function is lost develop age-related diseases or symptoms. In such knockout mice, bone mineral content, bone mineral density, and bone strength were found to be decreased, and the number of osteoclasts in bone tissues was found to be increased. Analysis of osteoclast-forming ability using bone marrow cells derived from the knockout mice revealed that osteoclast-forming ability is enhanced and osteoclasts are larger in the knockout mice than in wildtype mice. When purified S1-5 protein was added to this in vitro system, osteoclast-forming ability was inhibited. Furthermore, administration of purified S1-5 protein to osteoporotic model mice showed that this protein has the effect of improving osteoporosis. The above findings demonstrate that S1-5 protein is useful for treating and preventing age-related diseases such as osteoporosis.

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 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: 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 invention provides new, specific antigenic peptides from the protein GDF8. The invention also provides fusion proteins comprising the new peptides, immunogens and vaccines based on the new peptides and/or fusion proteins, antibodies that specifically bind to the new peptides of GDF8, and methods of treating animals in order to modulate the activity of GDF8, employing vaccines or antibodies according to the invention.

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: 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: The present inventors discovered that knockout mice whose S1-5 gene function is lost develop age-related diseases or symptoms. Histological analysis in such knockout mice revealed that bone mineral content, bone mineral density, and bone strength were decreased, and the number of osteoclasts in bone tissues was increased. Analysis of osteoclast-forming ability using bone marrow cells derived from the knockout mice revealed that osteoclast-forming ability is enhanced and osteoclasts are larger in the knockout mice than in wildtype mice. When purified S1-5 protein was added to this in vitro system, osteoclast-forming ability was inhibited.

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: A method of generating tissue from stem and progenitor cells is disclosed. Primary mammalian stem cells and progenitor cells are placed in an extracellular matrix. The matrix is maintained in a culture medium and a microgravity environment.

Abstract: The present invention provides RNAi agents targeted to sialidase. The RNAi agents include siRNA, shRNA, and expression vectors that comprise a template for transcription of an siRNA or shRNA. The invention further provides cells and cell lines that comprise an RNAi agent targeted to sialidase. The cells and cell lines exhibit reduced sialidase activity relative to control cells that do not comprise an RNAi agent targeted to sialidase. Certain of the cell lines stably express the RNAi agent. The invention further provides methods of producing the cells and cell lines. The invention further provides methods for producing a glycoprotein in cells that comprise an RNAi agent targeted to sialidase. The glycoproteins exhibit an improved sialic acid profile relative to glycoproteins produced by cells that do not comprise an RNAi agent targeted to sialidase. The invention further provides glycoproteins, e.g., therapeutic glycoproteins, produced in the cells.

Abstract: The present invention relates to a process for producing a desired polypeptide using rat cells. Specifically, the present invention relates to a process for producing the polypeptide which comprises culturing rat cells such as YB2/3HL.P2.G11.16Ag.20 (hereinafter referred to as YB2/0), preferably rat cells to which a recombinant DNA comprising DNA encoding a desired polypeptide such as an immunologically functional molecule is introduced, in a medium which does not contain serum (hereinafter referred to as a serum-free medium). Among the desired polypeptides obtained by the process of the present invention, an antibody obtained by using a transformant of YB2/0 has a high antibody-dependent cell-mediated cytotoxic activity (hereinafter sometimes referred to as ADCC activity) and is useful as a pharmaceutical agent.

Abstract: The present invention provides a method of identifying a modulator of a voltage gated sodium channel (VGSC), which method comprises bringing into contact a VGSC, a p11 peptide and a test compound under conditions where the VGSC and the p11 peptide are capable of forming a complex in the absence of the test compound; and measuring an activity of the VGSC, wherein a change in the activity of the VGSC relative to the activity in the absence of the test compound indicates that the test compound is a modulator of said VGSC. Compounds identified in such screening methods are proposed for use in the treatment of VGSC-related conditions, for example in the treatment or prevention of pain. Also provided are methods of enhancing the functional expression of a voltage gated sodium channel (VGSC) in a cell comprising the step of increasing the level of p11 in the cell.

Abstract: Methods and means for efficiently downregulating the expression of any gene of interest in eukaryotic cells and organisms are provided. To this end, the invention provides modified antisense and sense RNA molecules, chimeric genes encoding such modified antisense or sense RNA molecules and eukaryotic organisms such as plants, animals or fungi, yeast or molds, comprising the modified antisense and/or sense RNA molecules or the encoding chimeric genes.

Abstract: The use of mismatch repair (MMR) defective antibody producer cells offers a method to generate subclone variants with elevated protein production such as antibodies. Using MMR defective cells and animals, new cell lines and animal varieties with novel and useful properties such as enhanced protein production can be generated more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within host cells to alter endogenous genes that can yield increased titer levels of protein production. By employing this method, two genes were discovered whose suppressed expression is associated with enhanced antibody production. Suppressed expression of these genes by a variety of methods leads to increased antibody production for manufacturing as well as strategies for modulating antibody production in immunological disorders. Moreover, the suppression of these two genes in host cells can be useful for generating universal high titer protein production lines.

Abstract: This invention relates to multipotent stem cells, purified from the peripheral tissue of mammals, and capable of differentiating into neural and non-neural cell types. These stem cells provide an accessible source for autologous transplantation into CNS, PNS, and other damaged tissues.

Abstract: Methods of inducing differentiation of stem cells and stem cells obtained are disclosed. A method for stabilizing the phenotype of isolated primary cells in vitro is disclosed. In both methods, a central role is played by histone deacetylase inhibitors.

Abstract: This invention relates to the elucidation that TRPML3 is involved in salty taste perception in primates including humans and likely other mammals (given the significance of sodium and other ions to physiological functions and conditions this phenotype is likely strongly conserved in different animals). The invention also relates to the discovery that the TRPML3 gene also modulates one or more of sodium metabolism, sodium excretion, blood pressure, fluid retention, cardiac function and urinary functions such as urine production and excretion. The invention also relates to transgenic animals that have been engineered to express or knock out TRPML3 expression and assays using TRPML3 expressing animals, cells and isolated ion channel polypeptides for identifying compounds that modulate TRPML3-associated functions including salty taste, sodium metabolism, sodium excretion, blood pressure, fluid retention, cardiac function and urinary functions such as urine production and excretion.

Abstract: The present invention relates to the isolation, in vitro propagation, and transplantation and integration of non-pigmented retinal stem cells derived from the neuroretina of the eye, ex vivo and in vivo.

Abstract: The present invention describes novel compositions for deriving, maintaining and growing pluripotent and germ-line competent mammalian embryonic stem cells. The compositions of this invention refer to compositions comprising a 1) conditioned medium of a cell line expressing limited amounts of Leukemia Inhibitory Factor (LIF), 2) conditioned medium from a cell line transfected with mammalian LIF and 3) a medium supplemented with recombinant rabbit LIF. The present invention describes novel compositions for deriving, maintaining and growing adult human stem cells and/or adult early progenitor cells, preferably under stroma-free conditions and without added LIF and/or cytokines or growth factors. The media of the present invention are used for the generation of pluripotent and germ-line competent embryonic stem cells of mammals of which these cells were not obtained up to now. The media of the present invention are used for the generation of adult human stem cells and/or adult early progenitor cells.

Abstract: A canine respiratory coronavirus (CRCV) that is present in the respiratory tract of dogs with canine infectious respiratory disease and which has a low level of homology to the enteric canine coronavirus, but which has a high level of homology to all bovine coronavirus strains (e.g., Quebec and LY138) and human coronavirus strain OC43.

Abstract: A method of propagating mammalian endodermally derived progenitors such as hepatic progenitors, their progeny, or mixtures thereof is developed which includes culturing mammalian progenitors, their progeny, or mixtures thereof on a layer of embryonic mammalian feeder cells in a culture medium. The culture medium can be supplemented with one or more hormones and other growth agents. These hormones and other growth agents can include insulin, dexamethasone, transferrin, nicotinamide, serum albumin, ?-mercaptoethanol, free fatty acid, glutamine, CuSO4, and H2SeO3. The culture medium can also include antibiotics. Importantly, the culture medium does not include serum. The invention includes means of inducing the differentiation of the progenitors to their adult fates such as the differentiation of hepatic progenitor cells to hepatocytes or biliary cells by adding, or excluding epidermal growth factor, respectively.

Abstract: The present invention provides a serum-free supplement which supports the growth of hematopoietic cells in culture. Also provided are a medium comprising a basal medium supplemented with the serum-free supplement of the present invention. The present invention also provides methods for culturing and for differentiating hematopoietic cells.

Abstract: The present invention relates to a biological entity, notably a rat, carrying a regulator construct comprising a specific repressor gene and a responder construct comprising at least one segment corresponding to a short hairpin RNA (shRNA) or corresponding to complementary short interfering RNA (siRNA) strands or corresponding to miRNA, said at least one segment being under control of a promoter which contains an operator sequence corresponding to the repressor. The invention further relates to a method for preparing said biological entity and its use.

Abstract: The invention provides non-human transgenic animals, and cell lines, host cells, tissues and isolated organs, comprising the human UDP-glucuronosyltransferase IA (UGT1A) gene locus. In one aspect, the endogenous UGT1A gene locus of the non-human transgenic animal has been partially or completely “knocked out.” In another aspect, the invention is directed to drug screening, design and discovery. In another aspect, the invention is directed to determining the toxicity or metabolism of a compound, e.g., a toxin or drug, including environmental, dietary, cosmetic, biological warfare or other known or potentially toxic compounds. In another aspect, the invention is directed to deteuiining the toxicity or metabolism of a compound during a particular metabolic state of an animal, e.g., including pregnancy, stress, diet, age or a particular genotype.

Abstract: The invention provides a novel splice-variant of the ClC-4 protein, termed ClC-4A. ClC-4A is expressed in taste bud cells and is involved in sour taste perception. The invention provides ClC-4A polynucleotides and ClC-4A polypeptides, vectors, host cells and ClC-4A specific antibodies as well as designing high potency taste stimuli, determining taste preferences in animals, developing breed-specific foods, and modifying the taste of foods and medications.

Abstract: The present invention provides a process and kit for isolating cone photoreceptor cells from retinal tissue with a purity level of at least 80%, typically of about 90%. The isolation process uses a PNA-panning procedure conducted on dissociated retinal tissue. The present invention also provides a culture medium enabling the in vitro survival and development of such isolated cone cells. The means of the invention are applicable to adult mammalian cone cells, and more particularly to adult human cone cells. They have the advantage of being applicable to pathologic or otherwise altered cone cells, and thus give access to the screening of compounds capable of showing neuroprotective activity on adult cone cells.

Abstract: The present invention provides methods of propagating transformed neurons in a simulated microgravity environment generated by a rotating wall vessel (“3-D culture”) so that the phenotype of the transformed neurons so cultured becomes closer to that of non-transformed neurons (primary neurons) and less like the phenotype of transformed neurons cultured via standard cell culture techniques (“2-D culture”).

Abstract: The present invention concerns methods for the ex vivo formation of mammalian bone and subsequent uses of the bone. A critical and distinguishing feature of the present invention are defined tissue culture conditions and factors resulting in the formation of bone cell spheroids. The invention also provides for methods of implanting into subjects the ex vivo formed bone. Also described are methods for genetically altering the bone cell spheroids to affect bone formation, identification of candidate modulators of bone formation, and identification of genes involved in bone formation.

Abstract: A protein introduction method with which protein can be introduced into cells with excellent safety is provided. A target protein is supported on a carrier for protein introduction that is made from a clay mineral, and by adding this to cells it is possible to introduce the target protein into the cells. The clay mineral is preferably a layered clay mineral, and as the clay mineral it is possible to use montmorillonite, vermiculite, and illite, for example.

Abstract: An isolated mammalian extraembryonic endoderm-like cell line is provided. Methods for producing isolated mammalian extraembryonic endoderm-like cell line derived from a mammalian pluripotent stem cell culture are provided. Primate or human embryonic stem cells (ESCs) spontaneously generate the primate or human extraembryonic endoderm-like cell line wherein the extraembryonic endoderm-like cells sustain the pluripotence of the primate or human ESCs.

Abstract: The subject invention pertains to tumor cell lines useful for increasing the proliferation potential of any human or animal cell in culture, thereby providing immortalized or continuous cell lines and cultures. The invention also concerns proliferation factors, and compositions containing the factors, which are capable of increasing the proliferation potential of any human or other animal cell in culture. The subject invention further pertains to a method for proliferating cells in culture by containing cells with the proliferation factors. The proliferated cells can range in plasticity and can include, for example, blast cells, fertilized ova, non-fertilized gametes, embryonic stem cells, adult stem cells, precursor or progenitor cells, and highly specialized cells. Optionally, the cells can be induced to cease proliferation.

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: Compositions and methods are provided for treatment of autoimmune and other related diseases. 3d, a point mutation of the protein uncoordinated-93b (unc-93B), unc-93A, unc-93B, and unc-93C, polypeptides, nucleic acids encoding them and methods for making and using them, for example, to produce transgenic non-human animals.

Abstract: Disclosed are immunologically active antibodies directed against the CD20 antigen, as well as host cells comprising nucleic acid sequences encoding the light chains and heavy chains of immunologically active antibodies wherein the cell is capable of expressing and secreting an immunologically active chimeric anti-CD20 antibody and methods of using such host cells to make purified antibodies. The antibodies are useful for treating and diagnosing B cell disorders.

Abstract: The invention relates to a method for the production of a eukaryotic cell selectable by inactivation or reduction of an endogenous gene function, comprising the steps of (a) introduction of one or more vectors into the cell and (b) expression of a siRNA and preferably shRNA coded by the one or more vectors, directed against an endogenous selectable gene and inactivating same, said siRNA or shRNA being the transcription product of an RNAi selection cassette, the selection cassette comprising a section of at least 19 nucleotides of the transcribed region of the gene, said selection being operatively linked to a promoter and a transcription termination signal.

Abstract: Live cells obtained from a mammalian tissue or organ. The cells are maintained ex vivo on a porous membrane having a pore size of ?0.02 ?m at a physiologically acceptable pH, in the presence of a culture gas, in culture and in a culture medium. The inter-neighbour relationships and the signal transduction between the cells are retained.

Abstract: To provide an immortalized capillary pericyte line which maintains the original function/property of the cell line-deriving tissue, its establishment method, and the screening method for useful substance using the immortalized capillary pericyte line. Cerebral tissue of a transgenic rat carrying the large T antigen gene of SV40 thermo-sensitive mutant line tsA58 is homogenized and the resultant brain capillaries are treated with protease, thus obtained brain capillary cells are subcultured to establish an immortalized cell that expresses SV40 thermo-sensitive large T antigen, PDGF receptor ?, and Angiopoietin-1. In addition, the immortalized vascular pericyte line has ability to deposit calcium on matrix by dense culture.

Abstract: In vitro-differentiated retinal ganglion cells can be produced by exposing a mammalian retinal ganglion cell line to a protein kinase inhibitor. The differentiated retinal ganglion cells can be used to identify agents that protect retinal ganglion cells in vivo or in vitro from cell injury (including cell death) and agents that affect retinal ganglion cell ion channel activity.

Abstract: The objects of the present invention are to solve low test efficiency and low accuracy which are problems encountered in the conventional methods for testing myelotoxicity of a drug by observing smears. To this end, markers for discriminating and identifying hematopoietic stem cells and blood cells at various differentiation stages in bone marrow are identified. From this point of view, cell surface antigens are specified. Thus, it is found that the myelotoxicity of a drug can be evaluated with a high efficiency at a high accuracy by using flow cytometry to analyze for a change in the quantity of bone marrow-derived cells expressing the cell surface antigens after administration of the drug to an animal.

Abstract: This invention provides a novel transformed cell useful in constructing an anti-aging agent screening system, a screening method which uses the same and an anti-aging agent, and it relates to a transformed cell in which a gene coding for (a) a protein capable of phosphorylating p38 protein, or (b) p38 protein, a mutant of p38 protein, a kinase domain of p38 protein, a kinase domain of p38 protein mutant or a fusion protein containing them is transformed into a normal cell, a screening method which uses this transformed cell and an anti-aging agent which uses a compound obtained by the screening method as the active ingredient.

Abstract: Methods of activating a signaling cascade comprising, introducing leptin and/or a cytokine to a receptor complex comprising gp 130, optionally in combination with a compound acting on adenylate cyclase or acting on one or more downstream targets of adenylate cyclase, thereby inducing genes in neuro-endocrine cells or cells of neuro-endocrine origin. Two distinct gene-sets are induced, immediate early response genes (STAT-3, SOCS-3, Metallothionein-II, the serine/threonine kinase Fnk and the rat homologue of MRF-1), and late induced target genes (Pancreatitis Associated Protein I, Squalene Epoxidase, Uridinediphosphate Glucuronyl Transferase and Annexin VIII). Strong co-stimulation with the adenylate cyclase activator forskolin was shown with respect to late induced target genes. Transcripts encoding Leptin Induced Protein I (LIP-I) and Leptin Induced Protein II (LIP-II) were identified; however, no forskolin co-stimulatory effect was observed.

Abstract: A process for identifying compounds that can modulate the release of neuromediators is described in which, for example, at least one compound that is to be tested is brought into contact with a nerve tissue preparation and the possible modulating effect of the compound on release of neuromediator by the nerve tissue preparation is determined. Methods of preparing calibrated pieces of mammalian cerebral material and kits for the implementation of the process are also described.

Abstract: The invention relates to gene delivery vehicles which comprise nucleic acid molecules encoding apoptosis-inducing proteins VP2 and/or apoptin (VP3) like activity. VP2 and VP3 are viral proteins of the Chicken Anaemia Virus. Also, the invention relates to anti-tumor therapies. Infection of various human tumor cells with the gene delivery vehicles of the invention will result in the induction of apoptosis in tumor cells and much reduced apoptosis, if at all, in normal diploid, non-transformed/non-malignant cells. Also the invention relates to the diagnosis of cancer, and related forms of hyperplasia, metaplasia and dysplasia.

Abstract: The present invention provides amino acid sequences of peptides that are encoded by genes within the Human genome, the GPCR peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the GPCR peptides and methods of identifying modulators of the GPCR peptides.