Abstract: Disclosed are embryonic stem cell-derived dendritic cells, genetically modified immature dendritic cells capable of maturation, as well as methods for the production of such cells. In one embodiment, the cells made be produced by a method comprising the steps of providing a population of embryonic stem cells; culturing the embryonic stem cells in the presence of a cytokine or combination of cytokines which brings about differentiation of the embryonic stem cells into dendritic cells; and recovering the dendritic cells from the culture. In a further embodiment, the cells may be genetically modified.

Abstract: A viable global NaV1.7?/? knockout mouse is disclosed, and a breeding colony of global NaV1.7?/? knockout mice. Also disclosed are an isolated mouse gamete that does not encode a functional NaV1.7?/?, produced by the NaV1.7?/? knockout mouse; an isolated NaV1.7?/? mouse cell, or a progeny cell thereof, isolated from the NaV1.7?/? knockout mouse; and a primary cell culture or a secondary cell line and a tissue or organ explant or culture thereof derived from the NaV1.7?/? knockout mouse. Disclosed also are a hybridoma, wherein the hybridoma was originally formed from the fusion of the isolated NaV1.7?/? mouse cell mouse cell and a myeloma cell, and a method of making an antibody. Also disclosed are assays useful for screening prospective NaV1.7 inhibitors and dose ranging a test NaV17 inhibitor compound, which were validated using the NaV1.7?/? knockout mouse.

Abstract: A Factor VIII fusion protein or a Factor VIII fusion heterodimer comprising Factor VIII in which an amino acid sequence of a modulator is present in the B-domain, or an amino acid sequence of a modulator replaces some or all of the amino acid sequence of the B-domain is disclosed. Nucleic acids encoding the inventive fusion proteins and fusion heterodimers are also disclosed, as are methods for producing the fusion proteins and fusion heterodimers, pharmaceutical compositions, and methods of treating deficiencies in coagulation with the inventive fusion molecules.

Abstract: The invention relates to methods and kits for the quantitative analysis of in vivo mutation frequencies of the Pig-A gene in individuals exposed to a genotoxicant, particularly using peripheral blood samples of vertebrates.

Abstract: The invention relates to an ex vivo method for expanding monocytes, macrophages or dendritic cells, which method comprises inhibiting the expression or the activity of MafB and c-Maf in monocytes, macrophages or dendritic cells; and expanding the cells in the presence of at least one cytokine or an agonist of cytokine receptor signaling.

Abstract: Fetal blood multi-lineage progenitor cells that are capable of a wide spectrum of transdifferentiation are described.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

Abstract: The present invention provides human, rat and mouse NPC1L1 polypeptides and polynucleotides encoding the polypeptides. Also provided are methods for detecting agonists and antagonists of NPC1L1. Inhibitors of NPC1L1 can be used for inhibiting intestinal cholesterol absorption in a subject.

Abstract: The invention relates to a novel method for the exact determination of the binding of the Fc-part of IgG-antibodies to Fc-gamma receptors, and for the simultaneous examination of the antigen-specificity and the Fc-gamma-receptor activation, as well as specific materials for use in said method. The invention furthermore relates to a method for identifying substances that affect the binding of the Fc-part of IgG-antibodies to Fc-gamma receptors, on the basis of the method for the exact determination of the binding of the Fc-part.

Abstract: The present invention is a method for preparing a substantially pure population of endothelial progenitor cells wherein said cells express Flk-1, CD34, ?5?1 integrin fibronectin, and vWF and exhibit an adherent phenotype and methods for using the same to decrease the severity of lung injury, prevent pulmonary edema, restore endothelial barrier function, induce productive wound healing and angiogenesis, and increase survival rate in acute lung injury (ALI).

Abstract: Novel methods are disclosed for forming a heterodimeric receptor complex with IL-28R and CRF2-4. The methods may be used for detecting and treating viral infections in in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block ligand activity in vitro and in vivo. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

Abstract: The present invention relates a method for the enumeration of in vivo gene mutation. The method utilizes differential staining of GPI-anchor deficient erythrocyte populations to distinguish between wild-type and pig-a gene mutants. Quantitative analyses can be conducted on erythrocytes and/or reticulocytes, and is based upon fluorescent emission and light scatter following exposure to an excitatory light source. Counting of mutant erythrocytes or reticulocytes relative to the number of total erythrocytes or reticulocytes can be used to assess the DNA-damaging potential of an exogenous chemical agent, the DNA-damaging potential of an exogenous physical agent, the effects of an exogenous agent which can modify endogenously-induced DNA damage, and the effects of an exogenous agent which can modify exogenously-induced DNA damage. Kits for practicing the invention are also disclosed.

Abstract: The present disclosure relates to the finding that microRNA-146 plays a role in modulating the development and function of the immune system. Immune cell development and function can be modulated by delivery of microRNA-146 (miR-146) or antisense miR-146 to target immune cells or precursor cells. For example, in some embodiments, activity and/or proliferation of certain immune cells is regulated by administering miR-146 oligonucleotides or anti-miR-146 oligonucleotides. In other embodiments, pro-inflammatory cytokine expression in immune cells is regulated by administering a miR-146 oligonucleotide or anti-miR-146. In further embodiments, methods of regulating macrophage activity using antisense miR-146 are provided. Additional methods and compositions for regulating immune system function and development using miR-146 are disclosed.

Abstract: The present invention relates to methods of inducing expression of a polynucleotide encoding a therapeutic polypeptide, e.g., TNF-?, in a cell comprising contacting the cell with a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding the polypeptide, and at least one chemotherapeutic agent, wherein the chemotherapeutic agent induces expression of the polypeptide. The invention also relates to methods of inhibiting a neoplastic cell, comprising contacting the cell with a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding TNF-? and a chemotherapeutic agent. The present invention further relates to methods of inhibiting or reducing the growth of a tumor in a subject, comprising co-administering to the subject a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding TNF-? and a chemotherapeutic agent, wherein the co-administration inhibits or reduces the ability of the tumor to grow.

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 disclosure generally teaches compositions comprising SDF-1 mimetics and methods of using them to modulate an activity of a cell having an SDF-1 receptor by binding the SDF-1 receptor to an SDF-1 mimetic. The cell can be a hematopoietic cell, for example, and can be selected from a group consisting of hematopoietic stem cells, hematopoietic progenitor cells, primitive granulocytes, primitive erythroid cells, leukocytes, and neutrophils. In some embodiments, the activity can include the rate of multiplication of the cell or, where the cell is a quiescent cell, the binding can repress the activation of the quiescent cell. Other embodiments of the present invention are taught herein.

Abstract: The present invention pertains to the field of anti-cancer vaccines. More particularly, the invention concerns an optimized polypeptide, which comprises three cryptic tumor peptides with enhanced immunogenicity and comprises the amino acids sequence YLQVNSLQTVYLEYRQVPVYLEEITGYL (SEQ ID NO. 2), for use in an anti-cancer vaccine. Nucleic acids encoding such a polypeptide, as well as complexes and dendritic cells engineered with this polypeptide or a nucleic acid encoding it, are also part of the invention.

Abstract: The invention provides compositions and methods for the generation of novel non-human transgenic animals which contain an alteration in a gene of interest. These transgenic animals are capable of generating antibodies, e.g., human monoclonal antibodies, specific for the product of a gene of interest that has been functionally disrupted in the transgenic animal. Furthermore, the methods and compositions of the invention are suitable for use in the treatment, diagnosis, and imaging of disease.

Abstract: It is an object of the present invention to provide a method for efficiently preparing blood cells, such as mature megakaryocytes and platelets, from iPS cells in an in vitro culture system. The present invention provides a sac-like structure enclosing hematopoietic progenitor cells, which is obtained by inoculating iPS cells onto feeder cells and then culturing the iPS cells under conditions suitable for inducing the differentiation of hematopoietic progenitor cells. Moreover, the present invention also provides a method for producing various types of blood cells, which comprises culturing hematopoietic progenitor cells enclosed in the sac-like structure under conditions suitable for inducing the differentiation of blood cells. Furthermore, the present invention also provides a method for producing various types of blood cells, particularly megakaryocytes and platelets, without involving the sac-like structure.

Abstract: The present invention provides serum-free cell culture media formulations which are capable of supporting the in vitro cultivation of animal cells. The media comprise at least one nutrient of non-animal derivation, such as at least one plant peptide and/or at least one non-animal or plant lipid and/or fatty acid. The media may further optionally comprise an enzymatic digest or extract of yeast cells. The present invention also provides methods of cultivating animal cells in vitro using these cell culture media formulations. In addition, the media of the present invention can be used for growth of animal cells for virus production.

Abstract: Antibody expression vectors and plasmids can incorporate various antibody gene portions for transcription of the antibody DNA and expression of the antibody in an appropriate host cell. The expression vectors and plasmids have restriction enzyme sites that facilitate ligation of antibody-encoding DNA into the vectors. The vectors incorporate enhancer and promoter sequences that can be varied to interact with transcription factors in the host cell and thereby control transcription of the antibody-encoding DNA. A kit can incorporate these vectors and plasmids.

Abstract: The disclosure provides methods of modulating the activity of DDR1. Methods for screening for agents that activate DDR1 are disclosed. Methods for inducing the maturation of immature macrophages and immature dendritic cells are also disclosed. In addition, methods for increasing neutrophil activation using a DDR1 activating agent, and methods for increasing leukocyte migration using a DDR1 activating agent, are provided.

Abstract: Disclosed herein are methods and compositions for inactivating a glutamine synthetase (GS) gene, using fusion proteins comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding said fusion proteins are also provided, as are cells comprising said polynucleotides and fusion proteins.

Abstract: The present invention relates a method for the enumeration of in vivo gene mutation. The method utilizes differential staining of GPI-anchor deficient erythrocyte populations to distinguish between wild-type and pig-a gene mutants. Quantitative analyses can be conducted on erythrocytes and/or reticulocytes, and is based upon fluorescent emission and light scatter following exposure to an excitatory light source. Counting of mutant erythrocytes or reticulcoytes relative to the number of total erythrocytes or reticulocytes can be used to assess the DNA-damaging potential of an exogenous chemical agent, the DNA-damaging potential of an exogenous physical agent, the effects of an exogenous agent which can modify endogenously-induced DNA damage, and the effects of an exogenous agent which can modify exogenously-induced DNA damage. Kits for practicing the invention are also disclosed.

Abstract: The present invention provides platelet production methods. The method comprises the steps of providing a cellular material and culturing the cellular material, wherein platelets are produced. The culturing may be performed on 2D or 3D cell support structure or in suspension culture. In some embodiments, all or a part of the 2D or 3D culturing may be performed in a bioreactor. In some embodiments, the method may further comprise a step of isolating a subset of cells from the starting cellular material, wherein the isolated subset of cells is then cultured, wherein platelets are produced. In yet other embodiments, the method comprises the steps of providing a cellular material, isolating a subset of cells, seeding the subset of cells into a 3D scaffold, culturing the subset of cells in a 3D scaffold, seeding the cultured subset of cells into a bioreactor, culturing the subset of cells in a bioreactor, and harvesting the cells from the bioreactor, wherein platelets are produced.

Abstract: Methods for enhancing survival and/or proliferation of neural stem cells and pharmaceutical compositions containing neural stem cells prepared by such methods, together with methods for assaying factors enhancing survival and/or proliferation of neural stem cells and methods for screening for such factors. Either Galectin-1 is overexpressed in neural stem cells or neural stem cells are cultured in a liquid medium containing Galectin-1. Pharmaceutical compositions containing Galectin-1-overexpressing neural stem cells and pharmaceutical composition containing Galectin-1, prepared by the aforementioned methods, improve higher cerebral functions damaged by cerebral ischemia.

Abstract: Hematopoietic stem cells and methods for ex vivo expansion of hematopoietic stem cells are provided. The methods comprise culturing the cells in a media containing an effective amount insulin-like growth factor (IGF), fibroblast growth factor (FGF), thrombopoietin (TPO), and stem cell factor (SCF), under conditions sufficient for expansion of said cells. Methods for identifying expanded hematopoeitc stem cells and kits for ex vivo expansion of hematopoietic stem cells are also provided.

Abstract: The present invention provides for isolated nucleic acid sequences encoding viruses; isolated polypeptides comprising amino acid sequences of the virus; vectors comprising the viral nucleic acid sequences; cells comprising the vectors; antibodies and antigen binding fragments thereof which have binding specificity for the virus; methods of detecting or screening for the virus (e.g., in an individual); methods of identifying agents that inhibit the virus; methods of inducing an immune response to the virus; methods of treating disease associated with the presence of XMRV in an individual (e.g., cancer such as prostate cancer); methods of detecting asymptomatic cancer (e.g., prostate cancer); methods of identifying an individual at risk for developing cancer (e.g., prostate cancer); and kits for detecting the virus.

Abstract: The invention relates to the use of an expression vector construction coding for the functional HLA-DPal03?401 complex specifically identified by anti-HLA-DP antibodies, in order to create transgenic mice. The invention also relates to the use of the transgenic mice obtained, such as for the comparative preclinical study of the efficacy of vaccine candidates in order to asses the risks associated with the unwanted induction of an autoimmune disease and in order to determine a therapeutic strategy.

Abstract: A method of efficiently and conveniently inducing differentiation from bone marrow stromal cells to skeletal muscle cells, which comprises the steps of: (a) the step of adding one or more kinds of substances selected from the group consisting of a cyclic AMP increasing agent, a cAMP analogue, and a cell differentiation stimulating factor to a culture of bone marrow stromal cells, wherein said bone marrow stromal cells are not treated with a demethylating agent, and culturing the cells; (b) the step of introducing a Notch gene and/or a Notch signaling related gene into the cells obtained in the step (a), and culturing the cells to obtain a culture of myoblasts, provided that said culture does not contain the cells introduced with the gene and non-introduced cells; and (c) the step of adding a Notch ligand to the culture of myoblasts obtained in the step (b), and culturing the cells.

Abstract: The invention provides compositions and methods for cell separation. These reagents and techniques specifically agglutinate cells via surface antigen recognition and can be used to recover even rare cell types in high yield.

Abstract: Tolerogenic populations of dendritic cells are provided, where the dendritic cells are characterized by expression of select tissue-specific homing receptors including the chemokine receptors CCR9; or CMKLR1; or the integrin CD103. The dendritic cells may be conventional/myeloid or plasmacytoid dendritic cells. The cells may be isolated from lymphoid tissue, from blood, or from in vitro culture, e.g. bone marrow culture, etc. Methods are provided for their identification, isolation and targeting in immunotherapeutic interventions in suppressing inflammatory disorders including autoimmunity, transplantation responses and allergic diseases. In some embodiments dendritic cell populations are fixed to render them immunosuppressive, thus allowing the cells to be typed and banked for future use.

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: Fetal blood multi-lineage progenitor cells that are capable of a wide spectrum of transdifferentiation are described.

Abstract: Disclosed are immunostimulatory fusion proteins and methods for generating protective DC-induced, T cell-mediated immune responses in vitro and in vivo. The immunostimulatory fusion proteins comprise a polypeptide antigen component and an immunostimulatory component derived from the intracellular domain of the HER-2 protein. Also disclosed are immunostimulatory compositions comprising dendritic cells pulsed with such an immunostimulatory fusion protein and methods for immunotherapy using the compositions.

Abstract: Disclosed herein are methods of increasing the proliferation of non-tumorigenic B cells. The methods involve administering PCDGF and optionally other B cells stimulators (e.g., IgM, LPS) to B cells resulting in an increase in B cell proliferation. The methods of the invention can be used, for example, to establish B cells lines, to sort B cells from a mixed population of cells, or to activate resting B cells.

Abstract: Fetal blood multi-lineage progenitor cells that are capable of a wide spectrum of transdifferentiation are described.

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 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: Methods and compositions are provided for the isolation, culture and use of highly regenerative somatic mammalian cells. The cells are very small, and have an undefined nuclear structure. The cells may be isolated from fetal or adult tissues, and are found in tissue including, without limitation, fetal dermal tissue, blood, and bone marrow. The cells are characterized as expressing one or more markers selected from E-cadherin, integrin ?1, CXCR4, CD90 and CD34, and may be selected on the basis of such expression patterns.

Abstract: The invention is a method for analyzing immature reticulocytes for the presence of micronuclei. The method includes reticulocyte enrichment, fluorescent labeling, micronuclei staining, and analysis using single-laser flow cytometry. The invention also includes kits containing reagents to use in the method.

Abstract: The present invention provides in one aspect novel fusion partner cells that ectopically express one or more genes that alter the phenotype of a hybrid cell made from a fusion of the fusion partner cell and a fusion cell, hybrid cell lines produced using the fusion partner cells. The invention in another aspect provides antibodies produced by certain hybrid cell lines, and compositions containing one or a combination of such antibodies or antigen-binding fragments thereof. The invention also provides in another aspect methods of using the antibodies or antigen-binding fragments thereof for diagnosis and treatment of diseases characterized by the antigens specifically bound by the antibodies.

Abstract: The invention provides compositions and methods for cell separation. These reagents and techniques specifically agglutinate cells via surface antigen recognition and can be used to recover even rare cell types in high yield.

Abstract: The present invention relates to a soluble hybrid protein, comprising at least a first polypeptide sequence derived from a prion protein PrPc that is capable of binding a protein responsible for transmissible spongiform encephalitis (PrPSc), and a second polypeptide sequence (tag), wherein said hybrid protein does not comprise a functional membrane anchor moiety. Also, the present invention is directed to the use of said hybrid proteins for the diagnosis of transmissible spongiform encephalopathies. In addition, the present invention relates to the use of said hybrid protein, a nucleic acid encoding said hybrid protein, a vector, and/or a host cell comprising a nucleic acid encoding said hybrid protein for the preparation of a medicament for the prevention or treatment of transmissible spongiform encephalopathies (TSEs).

Abstract: The present invention is based on the discovery that in response to different stimuli, dendritic cells initiate various immune responses by producing different transcription profiles, e.g., IL-2 production by dendritic cells in response to a microbial stimulus. The present invention provides methods of making libraries of gene expression profiles and libraries made thereof corresponding to dendritic cell maturation in response to a microbial stimulation. The present invention provides methods for activating lymphocytes or immune responses and methods for producing Il-2 in dendritic cells or preparing dendritic cells for cell-based therapy. The present invention also provides methods and systems for screening agents affecting dendritic cell maturation. In addition, it is the discovery of the present invention that dendritic cells are targets for immunosuppressive virus infections.

Abstract: Gene complementation is used to restore cholesterol independence in NS lineage murine myeloma cells, such as NSO and NS 1, yielding a selectable system for recombinant production of polynucleotides and polypeptides.

Abstract: An object of the present invention is to provide a non-human animal model unresponsive to a mycoplasma-derived lipoprotein/lipopeptide, and a method for screening an inhibitor or a promoter for a response to a mycoplasma-derived lipoprotein with the use of the non-human animal model. A non-human animal model whose function of a gene that encodes a protein such as TLR6 that specifically recognizes a mycoplasma-derived lipoprotein is deficient on its chromosome, for example, a TLR6 knockout mouse, is generated. With the use of the non-human animal model unresponsive to a mycoplasma-derived lipoprotein or an immune cell such as a macrophage derived from the non-human animal model, a subject material and a mycoplasma-derived lipoprotein, a response to a mycoplasma-derived lipoprotein in the non-human animal model or the immune cell is measured/evaluated, and then an inhibitor or a promoter for a response to that is screened.

Abstract: The present invention relates to the use of L-?-lysophosphatidylcholine and/or an equivalent compound for the differentiation of monocytes into mature denditric cell. The present invention also relates to a method for differentiation monocytes into mature denditric cells according to which monocytes are provided in a medium suitable for their differentiation and L-?-lysophosphatidylcholine and/or an equivalent compound is added to said medium.

Abstract: Methods of inducing differentiation of mammalian bone marrow stromal cells into cells of multiple embryonic lineages by contacting marrow stromal cells with precursor differentiation-inducing compounds followed by contacting the partially differentiated precursor cells with specific cell type differentiation-inducing compounds. In one embodiment, the MSC derived precursor cell cultures comprise cells, at least some of which simultaneously express markers that are characteristic of endodermal and ectodermal cell types. In another embodiment, the differentiated cells are insulin-secreting pancreatic islet cells. Precursor differentiation-inducing compounds of the invention include anti-oxidants such as, but not limited to, beta-mercaptoethanol, dimethylsulfoxide, butylated hydroxyanisole, butylated hydroxytoluene, ascorbic acid, dimethylfumarate, and n-acetylcysteine.

Abstract: Molecular adjuvants are disclosed comprising an antigen presenting cell-targeting ligand linked to an immunogen. In particular, these molecular adjuvants are employed in compositions designed to deliver the specific immunogen to antigen presenting cells and simultaneously deliver signals to those cells that produce the desired immune response. Methods are also disclosed for delivery of these molecular adjuvants to patients, resulting in the transduction of activating signals to the targeted antigen presenting cell, thereby enhancing the immune response to the co-delivered immunogen.