Abstract: A fusion polypeptide comprising (A)x-M-(A?)y, wherein A and A? are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A? may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different ScFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.

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 PRO1105, PRO1279 or PRO1783 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: Disclosed is a method for preparing an embryonic stem cell (ESC)-like cell, which includes the steps of: (a) obtaining a first cell population from a mammalian tissue or body fluid, wherein the first cell population comprises adult stem cells; (b) obtaining a second somatic cell population from a mammalian tissue, wherein the mammalian tissue is different from the mammalian tissue in step (a) and the second cell population is different from the first cell population; (c) coculturing the first cell population and the second cell population in a medium for a period of time sufficient to form a colony from either the first cell population or the second cell population; and (d) subculturing a cell from the colony in a medium for a period time sufficient to prepare the ESC-like cell.

Abstract: The present invention provides a method for preparing a hair dermal papilla cell preparation comprising preparing a cell suspension by removing epidermal tissue from skin tissue and subjecting the resulting dermal tissue fraction to collagenase treatment, and cyropreserving the cell suspension to kill the follicular epidermal cells. The present invention also provides a composition for regenerating hair follicles comprising hair dermal papilla cell and epidermal cells, wherein the ratio of the number of hair dermal papilla cell to the number of epidermal cells is from 1:10 to 10:1.

Abstract: A transgenic non-human mammal with a disruption in its IL-21 receptor gene is provided, along with methods of using the transgenic non-human mammal.

Abstract: The invention provides methods for reprogramming somatic cells to generate multipotent or pluripotent cells. Such methods are useful for a variety of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a less differentiated state.

Abstract: The present invention relates to a pharmaceutical composition for treating rheumatoid arthritis, which comprises (a) a pharmaceutically effective amount of a semi-mature dendritic cell; and (b) a pharmaceutically acceptable carrier. The semi-mature dendritic cell of this invention has a safe and remarkably improved potential to treat or prevent rheumatoid arthritis through the activity of the suppression of auto-immune responses.

Abstract: Nucleic acids encoding various monocyte cell proteins from a primate, reagents related thereto, including specific antibodies, and purified proteins are described. Methods of using said reagents and related diagnostic kits are also provided.

Abstract: Nucleic acids encoding mammalian, e.g., primate, IL-1?, purified IL-1? polypeptides and fragments thereof. Binding proteins, e.g., antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are provided.

Abstract: Disclosed herein are methods for controlling stem cell differentiation through the introduction of transgenes having Xic, Tsix, Xite, or Xic flanking region sequences to block differentiation and the removal of the transgenes to allow differentiation. Also disclosed are small RNA molecules and methods for using the small RNA molecules to control stem cell differentiation. Also disclosed are stem cells genetically modified by the introduction of Xic, Tsix, XUe, or Xic flanking region sequences.

Abstract: A method of recovering mammalian cell clones adapted to serum and protein-free media is disclosed. The procedure includes a two-stage adaptation process to grow in that condition. A critical protein concentration interval is disclosed in which cells must grow in order to gain the capacity to survive in serum and protein-free condition, once the cells have grown at the critical interval concentrations, subsequent decreases of the concentration will affect neither viability nor cellular doubling time. The critical protein concentration interval is cell line specific. Furthermore, mammalian cells clones are disclosed, which are stable in serum- and protein-free media for at least 40 generations; additionally, clones disclosed express a recombinant product. The cell clones disclosed produce the humanized anti-EGF-R antibody hR3, the humanized anti-CD6 antibody T1hT, the chimeric anti CD3 antibody T3Q, or fragments thereof.

Abstract: Disclosed are methods for generating a neuron expressing Hoxc8 transcription factor or a caudal motor neuron comprising culturing an embryonic stem cell in a composition which is essentially free of retinoids and comprises an isotonic salt solution, so as to generate the neuron which expresses Hoxc8 transcription factor or the caudal motor neuron. Disclosed are also methods for generating a caudal brachial motor neuron, a thoracic motor neuron, or a lumbar motor neuron from an embryonic stem cell in a composition essentially free of retinoids and comprising ADFNK medium, an amount of FGF-2, or Gdf11 respectively. Disclosed are also methods of transplanting a motor neuron into a subject comprising generating the motor neuron and transplanting the motor neuron into the subject. Disclosed is also a population of motor neuron cells enriched for motor neuron cells expressing Foxp1 and expressing a gene associated with Spinal Muscular Atrophy (SMA) or Amyotrophic Lateral Sclerosis (ALS).

Abstract: To clarify histamine receptor H3 protein function in vivo, the present inventors constructed a nonhuman higher animal in which the expression of a histamine receptor H3 gene was artificially inhibited. As a result, the present inventors found that this nonhuman higher animal showed increased body weight, food intake, blood insulin level, or blood leptin level compared with a control. Thus, the present inventors found that abnormalities in the histamine receptor H3 protein relate to diseases characterized by changes in body weight or food intake, and this has made it possible to screen drugs for treatment or prevention of these diseases, and to examine these diseases.

Abstract: A kit and a method for determining modulating agents of sirtuins; specifically, the modulation of sirtuin expression, by way of the detection and comparison of mRNAs in the sirtuins and ?-actin. A process for modulating the activity of sirtuins, as well as pharmaceutical compounds and compositions capable of modulating the gene expression of sirtuins.

Abstract: The present invention provides systems and methods for improving the efficiency of a transient gene delivery system to differentiating embryonic stem (ES) cells by serum starving the targeted cells for one to three days prior to transfection. Such a serum starvation surprisingly resulted in increased expression of a constitutively-controlled plasmid from 50.4% to 83.2% of the population and increased expression of a promoter/enhancer controlled plasmid from ˜1.4% to ˜3.7% of the population.

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, hydrates, solvates and prodrug thereof, 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: The present invention is a new type of Glycine N-methyltransferase (GNMT) knockout mice model. This model can be applied to screen drug, test of treatment and search for diagnostic marker of hepatocellular carcinoma (HCC), glycogen storage disease, liver dysplasia, fatty liver and other liver disease.

Abstract: A composition and method for in vitro fertilization is provided which uses culture media comprising elevated concentrations of lipoic acid. More specifically, the invention provides culture media for developmental cells having a lipoic acid concentration of 5 ?M to 40 ?M. Culture media that include lipoic acid at concentrations within the identified range are able to provide blastocysts with increased survival, increased cell numbers, increased inner cell masses and/or increased percentage of the total mass made up by the inner cell compared to blastocysts cultured in a control medium.

Abstract: This invention relates to industrial production of proteins. More specifically, the invention relates to the res-DHFR surrogate marker, which corresponds to a fusion between DHFR and a protein conferring resistance to a toxic compound or conferring a metabolic advantage. The invention further relates to the use of res-DHFR for screening cells for high expression of a protein of interest. The invention is illustrated by the Puro-DHFR surrogate marker, which corresponds to a fusion between the puromycin N-acetyltransferase and dihydrofolate reductase (DHFR).

Abstract: The invention provides a non-human mammal or a cell line that has a targeted gene disruption in an endogenous Iqgap2 gene. The invention also provides methods of identifying a compound as a therapeutic agent for the treatment of hepatocellular carcinoma and methods of treating or preventing hepatocellular carcinoma.

Abstract: The disclosure provides an expression cassette and a vector comprising the cassette for expression of a polynucleotide. The expression cassette includes a promoter/enhancer, an intervening region, and a polyadenylation signal domain. Expression systems and methods of using the expression cassette and vector are also provided.

Abstract: The present invention generally relates to humanized VEGF and non-human transgenic animals expressing it. The transgenic animals are also useful to study VEGF-related therapies.

Abstract: A method of making a genetically modified mammalian cell, the method including selecting a first codon of a parent polynucleotide that encodes a polypeptide for replacement with a synonymous codon, wherein the synonymous codon is selected on the basis that it exhibits a higher translational efficiency in a first type of mammalian cell than the first codon in a comparison of translational efficiencies of codons in cells of the first type, replacing the first codon with the synonymous codon to form a synthetic polynucleotide, and introducing the synthetic polynucleotide into a mammalian cell to produce the genetically modified mammalian cell.

Abstract: The present invention provides a novel isolated mesenchymal cell population of highly purified osteoprogenitors (HipOPs) that can be used in the formation of bone tissue and methods for isolating and using same.

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-modulated 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: Pluripotency determining factors are described which act intracellularly and maintain a pluripotent cell in a pluripotent state in the absence of gp130 activation, which maintain or confer pluripotency of a human stem cell, which maintain or confer pluripotency of a mouse ES cell, and which maintain or confer pluripotency of a stem cell from a non-permissive strain of mice. The factors and vectors encoding or activating the factors are used to maintain and derive pluripotent cells, especially of higher mammals, including humans.

Abstract: The invention provides methods for reprogramming somatic cells to generate multipotent or pluripotent cells. Such methods are useful for a variety of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a less differentiated state.

Abstract: The present invention provides methods for designing a sequence for efficient short interference RNA molecules. In particular, the present invention defines a universal target for siRNA derived from a poly A sequence, optionally in conjunction with unique sequences for gene silencing and inhibition of viral replication in a eukaryotic host cell. The present invention further provides methods for the treatment and prevention of diseases and disorders by silencing a gene of a virus, an oncogene, genes encoding transcription factors and many other diseases related genes. The present invention describes antisense nucleic acids compositions comprising sequences complementary to a target nucleic acid. The antisense sequences are designed to hybridize to complementary nucleic acid target regions in a target RNA, and inhibit translation, processing, transport, or binding by proteins or riboproteins.

Abstract: The present invention relates to photoreceptor cells. In particular, the present invention provides photoreceptor cells comprising heterologous nucleic acid sequences and transgenic animals comprising the same. The present invention also provides photoreceptor precursor cells (e.g., rod photoreceptor precursor cells), and methods of identifying, characterizing, isolating and utilizing the same. Compositions and methods of the present invention find use in, among other things, research, clinical, diagnostic, drug discovery, and therapeutic applications.

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: The present invention provides a method for preparing a hair dermal papilla cell preparation comprising preparing a cell suspension by removing epidermal tissue from skin tissue and subjecting the resulting dermal tissue fraction to collagenase treatment, and cyropreserving the cell suspension to kill the follicular epidermal cells. The present invention also provides a composition for regenerating hair follicles comprising hair dermal papilla cell and epidermal cells, wherein the ratio of the number of hair dermal papilla cell to the number of epidermal cells is from 1:10 to 10:1.

Abstract: The invention relates to mice having functionally silenced endogenous lambda (?) and kappa (?) L-chain loci, comprising antibody-producing cells in which the CH1 domain is functionally silenced, either via spontaneous processes in somatic antibody-producing cells or due to germline deletion of the CH1 domain. Mice of the invention are capable of producing H-chain-only antibody lacking a functional CH1 domain; transgenic human heavy-chain-only antibodies lacking a functional CH1 domain can be produced following insertion into the mouse of an artificial locus with human heavy chain V, D and J segments and a constant region, which is preferably a modified constant region with alterations in, around or upstream of a CH1 domain and/or removal of a CH1 domain.

Abstract: The present invention relates to nucleic acid sequences coding for modified coagulation factors, preferably coagulation factor VIII, and their derivatives; recombinant expression vectors containing such nucleic acid sequences; host cells transformed with such recombinant expression vectors; and recombinant polypeptides and derivatives coded for by said nucleic acid sequences, whereby said recombinant polypeptides and derivatives have biological activities and prolonged in vivo half-lives compared to the unmodified wild-type proteins. The invention also relates to corresponding sequences that result in improved in vitro stability. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such nucleic acid sequences.

Abstract: A method of enhancing in vitro development of a mammalian embryo is disclosed which comprises supplementing the culture medium with a prostaglandin, or a prostaglandin analog, in an amount effective to promote complete hatching of the embryo (i.e., freeing of the embryo from the zona pellucida). The quality of human blastocysts is enhanced in vitro by culturing with a prostacyclin agonist, Iloprost. The in vivo implantation potential and live birth potential of an in vitro fertilization embryo is thereby enhanced and establishment of a viable pregnancy is facilitated.

Abstract: Nucleic acids encoding mammalian, e.g., primate or rodent, genes, purified 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: Compositions and methods are provided for the reproducible derivation of germ cells and oocytes and spermatogonia therefrom. Also provide are methods of use of the same in reproductive and therapeutic cloning protocols.

Abstract: The present invention is directed to methods using transgenic mice to screen for biologically active agents.

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: Novel CC chemokines from human, reagents related thereto including purified proteins, specific antibodies and nucleic acids encoding these chemokines are provided. Also provided are methods of making and using said reagents and diagnostic kits.

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 cell which is suitable for screening a candidate agent as being an inhibitor of the metabolism of tryptophan to NAD+ and/or a modulator of NAD+ levels, which cell comprises functional genes of a pathway enabling the metabolism of tryptophan to NAD+ and wherein the cell includes a copy of an exogenous gene of said pathway, from the same or different species as the cell, which exogenous gene is under the control of an inducible or constitutive promoter and wherein any endogenous copy of the gene having the same function as the exogenous gene is a non functioning gene. The present invention also relates to populations of such cells and to methods of screening candidate agents with such cells.

Abstract: Pluripotency determining factors are described which act intracellularly and maintain a pluripotent cell in a pluripotent state in the absence of gp130 activation, which maintain or confer pluripotency of a human stem cell, which maintain or confer pluripotency of a mouse ES cell, and which maintain or confer pluripotency of a stem cell from a non-permissive strain of mice. The factors and vectors encoding or activating the factors are used to maintain and derive pluripotent cells, especially of higher mammals, including humans.

Abstract: The present invention provides isolated monoclonal antibodies, particularly human antibodies, that bind to IP-10 with high affinity, inhibit the binding of IP-10 to its receptor, inhibit IP-10-induced calcium flux and inhibit IP-10-induced cell migration. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting IP-10 activity using the antibodies of the invention, including methods for treating various inflammatory and autoimmune diseases.

Abstract: Compositions and methods are provided herein for the expression of nucleic acids. Compositions and methods are also provided herein for inducible expression of nucleic acids in transgenic cells and animals using transposon-based nucleic acid constructs. Compositions and methods are also provided herein for modulation of endogenous gene expression.

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: A transgenic mouse model for colorectal cancer, pulmonary emphysema or cardiomyopathy comprises a transgenic mouse that produces suboptimal levels of latent transforming growth factor ? binding protein 4 (LTBP-4). The transgenic mouse includes a mutation resulting in homozygous disruption of both endogenous alleles of a gene encoding LTBP-4, and develops colorectal cancer, pulmonary emphysema or cardiomyopathy.

Abstract: This application relates to a newly identified animal cell structure, the midbody scar. This structure is a remnant of the midbody that is retained by one daughter cell following cytokinesis and persists through multiple subsequent cell cycles. The midbody scar can be useful as a marker of dividing cells or of a cell's replicative age.

Abstract: The present invention provides an isolated polynucleotide comprising or consisting of the nucleotide sequence encoding the G protein of human respiratory syncytial virus (RSV), wherein the nucleotide sequence is codon optimised for expression in mammalian cells and wherein the polynucleotide provides increased expression of the G protein in mammalian cells relative to expression of the wildtype RSV-G gene. Preferably, the polynucleotide comprises or consists of the nucleotide sequence of SEQ ID NO:2. Further aspects of the invention provide pharmaceutical compositions, in particular vaccines, for use in methods of immunising a subject against RSV infection.

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.