Abstract: The present invention provides isolated polynucleotides that can serve as translation enhancing elements and their use in protein expression reagents and methods.

Abstract: Provided herein are mitochondrial-nuclear exchanged cells and animals comprising mitochondrial DNA (mtDNA) from one subject and nuclear DNA (nDNA) from a different subject. Methods for producing a mitochondrial-nuclear exchanged animal and animals made by the methods are provided. Also provided are methods of screening for agents useful for treating a disease or disorder using mitochondrial-nuclear exchanged animals or cells, tissues or organs thereof.

Abstract: The invention concerns the field of recombinant gene engineering. It concerns novel introns and compositions comprising such introns as well as a method to improve expression of polypeptides from nucleic acids such as cloned genes with heterologous introns, especially genes encoding antibodies and antibody derived fragments, and the production of various polypeptides in eukaryotic host cells using said novel intron sequences as heterologous introns.

Abstract: The present disclosure provides methods of generating neural stem cells from differentiated somatic cells. The present disclosure also provides induced neural stem cells generated using a subject method, as well as differentiated cells generated from a subject induced neural stem cell. A subject neural stem cell, as well as differentiated cells derived from a subject neural stem cell, is useful in various applications, which are also provided in the present disclosure.

Abstract: The present inventors discovered that genes could be introduced specifically into trophectodermal cells with high efficiency, by infecting blastocysts with viral vectors carrying an arbitrary polynucleotide, or by using a nucleic acid transfection reagent in blastocysts, from which zona pellucida (extracellular matrix covering preimplantation early embryos to protect them from infection of viruses and the like) is removed. This method has no risk of infecting cells of the inner cell mass, which develops into a fetus in the future, with the introduced polynucleotide because the trophectoderm serves as a barrier. The present invention provides methods for introducing foreign genes into only placenta but not fetus, which enables rescue of genetically mutant animals from embryonic lethality due to placental abnormality and allows their birth. Furthermore, it is possible to analyze expression and effect of genes that regulate placental formation or placental function by using these methods.

Abstract: Neuroinvasive and neurovirulent strain of the West Nile virus, named IS-98-ST1, nucleic acid molecules derived from its genome, proteins and peptides encoded by said nucleic acid molecules, and uses thereof.

Abstract: The present invention relates to transgenic non-human animals that are engineered to contain human immunoglobulin gene loci. In particular, animals in accordance with the invention possess human Ig loci that include plural variable (VH and V?) gene regions. Advantageously, the inclusion of plural variable region genes enhances the specificity and diversity of human antibodies produced by the animal. Further, the inclusion of such regions enhances and reconstitutes B-cell development to the animals, such that the animals possess abundant mature B-cells secreting extremely high affinity antibodies.

Abstract: In one aspect, the disclosure relates to compositions comprising alpha-1-antitrypsin (AAT) and the production thereof. In some embodiments, the AAT is recombinantly produced. The disclosure also relates to methods of administering compositions comprising alpha-1-antitrypsin (AAT).

Abstract: Genetically modified somatic cells of a non-human animal are provided that are engineered to contain a self-excisable, recombinase expression cassette comprising a site-specific recombinase gene operably linked to an ES cell-specific promoter. Compositions and methods for producing a genetically modified, cloned non-human animal that is free of a selective marker gene and a recombinase gene are provided, wherein a targeting construct comprising a self-excisable recombinase gene operably linked to an ES cell-specific promoter is introduced into differentiated somatic cells. The genetically modified genome of the somatic cells is transferred into an enucleated host oocyte. The artificially created zygote is then cultured in vitro until the blastocyst embryonic stage and subsequently implanted into a uterus of a surrogate mother to form a genetically modified, cloned non-human animal free of selective marker and recombinase genes.

Abstract: Techniques for generating microtissues, including a micro-fabricated platform including at least one micro-well including a plurality of micro-cantilevers coupled thereto and surrounded by a plurality of ridges, each micro-cantilever including a cap at a terminal end thereof. The platform can be immersed in a suspension of cells. The suspension of cells can be driven into at least one micro-well, and the ridges can be de-wetted to remove excess suspension and isolate the suspension of cells in each micro-well. The cells can be driven in the suspension of each micro-well toward a top surface of the suspension, which can be polymerized to form a matrix. The cells can be cultivated to spontaneously compact the matrix such that the micro-cantilevers anchor and constrain the contracting matrix to form a band of microtissue that spans across the micro-cantilevers.

Abstract: The present invention relates to antibodies against human collagen II, polypeptides and polynucleotides encoding human collagen II antibodies or fragments thereof, and methods of making and using the foregoing.

Abstract: Methods of treating individuals with a glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.

Abstract: The present invention is concerned with nuclease fusion proteins and various uses thereof. Specifically, it relates to a polynucleotide encoding a polypeptide comprising (i) a first module comprising at least a first DNA binding domain derived from a homing endonuclease, (ii) a linker, and (iii) a second module comprising at least a second DNA binding domain and a cleavage domain derived from a restriction endonuclease, wherein said polypeptide functionally interacts only with DNA comprising a DNA recognition site for the first DNA binding domain and a DNA recognition site for the second DNA binding domain, and wherein said cleavage domain cleaves DNA within a specific DNA cleavage site upon binding of the polypeptide. Further contemplated are a vector and a non-human transgenic organism comprising said polynucleotide as well as a polypeptide encoded by the polynucleotide of the invention.

Abstract: IL4/IL13-binding proteins comprise binding domains, which inhibit IL4/IL13 binding to IL4Ralpha and common gamma chain complexes (Type 1) and inhibit IL4 binding to IL4Ralpha and IL13Ralpha1 complexes (Type 2), and IL13 binding to IL13Ralpha1 and/or IL13Ralpha2, are useful in the treatment of cancer, inflammatory, and other pathological conditions, such as allergic or fibrotic conditions, especially pulmonary conditions.

Abstract: Genetically modified mammals are described which lack the mannan binding lectin associated serine protease MASP-2, together with methods and constructs for their production. Such mammals are useful as models for disorders of the complement system, and in the identification of treatments for such disorders. Also described are mammals which lack the associated protein MAp19; such mammals may also lack MASP-2.

Abstract: An object of the present invention is to provide a method of producing intestinal cells by use of pluripotent stem cells as a starting material. According to the present invention, provided is a method of producing intestinal cells, comprising the steps of: (A) inducing differentiation of pluripotent stem cells into definitive endoderm cells; and (B) culturing the definitive endoderm cells in the presence of (2?Z,3?E)-6-bromoindirubin-3?-oxime (BIO) and N-[(3,5-difluorophenyl)acetyl]-L-Ala-2-phenyl-L-Gly-tert-butyl-OH (DAPT) to thereby induce differentiation of the definitive endoderm cells into intestinal cells.

Abstract: The disclosed invention relates to the observation that nestin expression is a marker for endothelial cell proliferation. Nestin expression is particularly useful as a marker for angiogenesis, particularly for tumor-related angiogenesis. Specifically, nestin serves as an excellent endothelium marker for brain tumors such as gliomas, hemangioblastomas, Schwannomas, medulloblastomas, and meningiomas. Accordingly, the disclosed invention relates to the use of this marker as a basis to model angiogenic activity.

Abstract: The present invention relates generally to a method of modifying gene expression and to synthetic genes for modifying endogenous gene expression in a cell, tissue or organ of a transgenic organism, in particular a transgenic animal or plant. More particularly, the present invention utilizes recombinant DNA technology to post-transcriptionally modify or modulate the expression of a target gene in a cell, tissue organ or whole organism, thereby producing novel phenotypes. Novel synthetic genes and genetic constructs which are capable of repressing delaying or otherwise reducing the expression of an endogenous gene or target gene in an organism when introduced thereto are also provided.

Abstract: Disclosed is a composition for reprogramming somatic cells to generate embryonic stem cell-like cells, comprising: a) a Bmi1 (B cell-specific Moloney murine leukemia virus integration site 1) protein or a nucleic acid molecule coding for Bmi1; and b) an Oct4 protein or a nucleic acid molecule coding for Oct4. Also, a method is provided for reprogramming somatic cells to generate embryonic stem cell-like cells using the composition. In addition to reducing the number of the genetic factors conventionally needed, the composition and method allow the generation of pluripotent embryonic stem cell-like cells which have high potential in the cell therapy of various diseases.

Abstract: The present invention provides a method of artificially repressing gene expression, which is simpler to design than conventional methods (the RNAi, ribozyme and antisense methods) and which allows for easier confirmation of the effect. A method of inhibiting the translation reaction of a target gene, comprising cutting out a part of the poly(A) tail and/or 3?-terminal sequence of the target mRNA is provided.

Abstract: Binding agents that modulate the immune response are disclosed. The binding agents may include soluble receptors, polypeptides, and/or antibodies. Also disclosed are methods of using the binding agents for the treatment of diseases such as cancer.

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 invention relates generally to beta (1,4)-galactosyltransferase I mutants having altered donor and acceptor specificities, and methods of use thereof. In addition, the invention relates to methods for synthesizing oligosaccharides using the beta (1,4)-galactosyltransferase I mutants and to using the beta (1,4)-galactosyltransferase I mutants to conjugate agents, such as therapeutic agents or diagnostic agents, to acceptor molecules.

Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.

Abstract: The present invention provides, as an enzyme which can be used for enzyme replacement therapy for Fabry disease, a protein having ?-galactosidase activity, which shows no allergic adverse side effect, shows a high stability in blood, and can be easily incorporated into a cell of an affected organ. The protein of the present invention is a protein which has acquired ?-galactosidase activity by changing the structure of the active site of wild-type human ?-N-acetylgalactosaminidase.

Abstract: Provided is a method of dedifferentiating somatic cells using embryonic stem cell-derived microvesicles. Particularly, a method of preparing induced pluripotent stem cells by treating a composition including embryonic stem cell-derived microvesicles to the somatic cells. According to the method of preparing induced pluripotent stem cells, the dedifferentiation of the somatic cells may be efficiently performed without side effects using the embryonic stem cell-derived microvesicles, and moreover, the method is expected to be very useful in developing a cell therapy product having immunocompatibilities by individuals.

Abstract: The present invention relates to the use of a female germinal cell (egg) extract of pluricellular organisms in M-phase of the cell cycle for a mitotic remodeling of chromosomes of donor cells of pluricellular organisms, wherein the mitotic remodeling confers to the nucleus of the donor cells the ability to adapt themselves to the early embryonic development, in particular to the replication phases, in order to carry out the embryonic development or to obtain stem cells.

Abstract: Provided are compositions, kits, and methods for separating cells including complexes of at least one type of linker capable of binding to an antibody or antigen binding fragment and a solid phase.

Abstract: The present disclosure provides for and relates to novel fusion proteins and polypeptides expressed by breast cancer and other cancer cells, and to compositions, materials and methods for detecting, characterizing and treating said breast and other cancers. In one embodiment, the fusion polypeptides are read-through fusion transcripts.

Abstract: Disclosed are an amphipathic peptide-lipase conjugate with enhanced lipase activity, a polynucleotide coding for the conjugate, an expression vector carrying the polynucleotide, a transformant anchoring the expression vector therein, a method for preparing the conjugate, a lipolysis method using the conjugate, and a method for producing biodiesel using the lipase.

Abstract: A main object of the present invention is to provide a technique to produce iPS cells with less burden on the patient and with high establishment efficiency. iPS cells can be efficiently produced with significantly improved establishment efficiency by selecting cells derived from oral mucosa and introducing, into the cells, reprogramming factors capable of inducing the cells into pluripotent stem cells.

Abstract: Provided are antibodies specifically binding to the epidermal growth factor receptor (EGFR) which are effective for the treatment of EGFR-mediated cancers.

Abstract: Choroid plexus epithelial cells are generated in a culture medium using embryonic stem cells and adding an effective amount of bone morphogenetic protein and/or other members of the transforming growth factor beta (TGF-beta) superfamily. Generation of such choroid plexus epithelial cells are confirmed using a combination of genetic markers, antibodies, histology inspection, functional assays, and integration into the endogenous choroid plexus in mice.

Abstract: Monospecific and bispecific EGFR and/or c-Met FN3 domain containing molecules, isolated nucleotides encoding the molecules, vectors, host cells, and methods of making thereof are useful in the generation of therapeutic molecules and treatment and diagnosis of diseases and disorders.

Abstract: Monospecific and bispecific EGFR and/or c-Met FN3 domain containing molecules, isolated nucleotides encoding the molecules, vectors, host cells, and methods of making thereof are useful in the generation of therapeutic molecules and treatment and diagnosis of diseases and disorders.

Abstract: A method of deriving isolated stem cells including: implanting a matrix in a wound site of a living organism; allowing cells to infiltrate the matrix; removing the matrix containing the infiltrated cells from the wound site; and removing the infiltrated cells from the matrix to provide isolated stem cells. Stem cells produced by this process, stem cells with certain characteristics, and methods for treating wounds using these stem cells are provided.

Abstract: DNA clones encoding a receptor in the Ig superfamily and a related soluble variant have been isolated from a human monocyte library. The invention provides receptor polypeptides, nucleic acids encoding them, expression vectors, and transformed cells for recombinant production of the polypeptides.

Abstract: The present invention relates to methods for culturing human retinal progenitor cells under low oxygen conditions to allow the cells to retain the ability to differentiate into photoreceptors following transplantation. The described methods provide cells that can treat a number of ocular diseases, including retinitis pigmentosa and age-related macular degeneration.

Abstract: DNA clones encoding a receptor in the Ig superfamily and a related soluble variant have been isolated from a human monocyte library. The invention provides receptor polypeptides, nucleic acids encoding them, expression vectors, and transformed cells for recombinant production of the polypeptides.

Abstract: The present invention relates to the field of biotechnology or genetic engineering. More specifically, the present invention relates to a multiple inducible gene regulation system that functions within cells to simultaneously control the quantitative expression of multiple genes.

Abstract: The present invention provides novel mammalian alpha-kinase proteins: melanoma alpha-kinase (MK), heart alpha-kinase (HK), kidney alpha-kinase (KK), skeletal muscle alpha-kinase (SK), and lymphocyte alpha-kinase (LK). In particular, a novel kinase type is herein provided, characterized by the presence of an alpha-kinase catalytic domain and an ion channel domain. Isolated nucleic acids of the alpha-kinases MK, HK, KK, SK and LK are provided. Methods for making the novel alpha-kinases, cells that express the alpha-kinases and methods for treating an animal in need of either increased or decreased activity of the alpha-kinases are provided.

Abstract: Disclosed herein are polypeptides, polynucleotides encoding, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences.

Abstract: The present disclosure is directed to the development of compositions, such as extracellular matrices, and processes for using the same, for culturing stem cells in vitro in an undifferentiated state. In this regard, it has been discovered that when pluripotent mouse and human embryonic stem cells are cultured on plates coated with recombinant laminin-10 (laminin-511) or laminin-5 (laminin-322), or their functional domains, the embryonic stem cells proliferated and maintained their pluripotency.

Abstract: IL4/IL13-binding proteins comprise binding domains, which inhibit IL4/IL13 binding to IL4Ralpaha and common gamma chain complexes (Type 1) and inhibit IL4 binding to IL4Ralpha and IL13Ralpha1 complexes (Type 2), and IL13 binding to IL13Ralpha1 and/or IL13Ralpha2, are useful in the treatment of cancer, inflammatory, and other pathological conditions, such as allergic or fibrotic conditions, especially pulmonary conditions.

Abstract: Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.

Abstract: The invention relates to mTORbeta, a splice form of mTOR, nucleic acids encoding mTOR beta, and antibodies against mTOR beta. The invention also relates to methods of producing mTOR beta and methods of screening for an agent that modulates mTOR beta expression and/or activity. The invention further relates to a method of treating a disease associated with aberrant expression of mTOR beta by administration of an agent that alters mTOR activity and/or expression.

Abstract: The present invention provides improved fusion proteins for therapy of autoimmune and cardiovascular disease.

Abstract: The present invention relates to novel therapies for treatment of new and existing type 1 and type 2 diabetes, PreDiabetes, Latent Autoimmune Diabetes of Adulthood, and diseases of insulin deficiency, beta cell deficiency, insulin resistance and impaired glucose metabolism. In particular, the present invention identifies common peptides within the human Reg1a, Reg1b, Reg3a and Reg4, as signaling peptides for beta cell generation acting through the human Reg Receptor on the surface of human pancreatic extra-islet tissue.

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) targeting an APOC3 gene, and methods of using the dsRNA to inhibit expression of APOC3.

Abstract: In one aspect, the invention provides a transgenic non-human animal model havings germ cells and somatic cells containing an endogenous MMTV-SV40-Spy1A gene sequence introduced into said animal model, or an ancestor of said animal model at an embryonic stage, wherein said gene sequence comprises a mouse mammary tumor virus gene (MMTV), a functionally disrupted SV40 gene (SV40) and a human Spy1A gene. In another aspect, the present invention provides a transgenic non-human animal model whose germ cells and somatic cells contain an endogenous Spy1A-pTRE-Tight gene sequence introduced into said animal model or an ancestor of said animal model at an embryonic stage. Preferably, the Spy1A-pTRE-Tight animal model expresses the Spy1A and develop cancer, preferably breast cancer, when administered with tetracycline, preferably doxycycline.