Abstract: The present invention provides compositions and methods for the culture and maintenance of pluripotent stem cells. More particularly, the present invention provides for compositions and methods for culturing, maintaining, growing and stabilizing primate pluripotent stem cells in a feeder-free defined media further comprising human serum, or a soluble attachment component of the human serum, for promoting cell attachment.

Abstract: We disclose a particle comprising a matrix coated thereon and having a positive charge, the particle being of a size to allow aggregation of primate or human stem cells attached thereto. The particle may comprise a substantially elongate, cylindrical or rod shaped particle having a longest dimension of between 50 ?m and 400 ?m, such as about 200 ?m. It may have a cross sectional dimension of between 20 ?m and 30 ?m. The particle may comprise a substantially compact or spherical shaped particle having a size of between about 20 ?m and about 120 ?m, for example about 65 ?m. We also disclose a method of propagating primate or human stem cells, the method comprising: providing first and second primate or human stem cells attached to first and second respective particles, allowing the first primate or human stem cell to contact the second primate or human stem cell to form an aggregate of cells and culturing the aggregate to propagate the primate or human stem cells for at least one passage.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a Group H nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: The present invention relates to a method for improving viability and/or stress tolerance of viable biological material and using the said material comprising applying hydrostatic pressure to said biological material; keeping the said viable biological material at the hydrostatic pressure for a predetermined time period; releasing the hydrostatic pressure; and using the said material for any desired purpose in accordance with any useful protocol. The usage of the said biological material incorporates any techniques, protocols that are applicable in the field of assisted reproductive techniques, biotechnical and/or biotechnological manipulations.

Abstract: The present invention provides novel stem cells, nucleotide sequences and proteins therefrom. More specifically, the present invention provides Pax7+/Myf5? stem cells and methods for identifying and isolating them. Also provided is a MEGF10 nucleotide sequence and protein.

Abstract: The present invention relates to permanent cell lines from chiropterans suitable for amplification and production of microbial agents, preferably viruses, and its use for diagnostic or therapeutic purposes.

Abstract: The present invention relates to a delivery system that comprises a conjugate that facilitates the delivery of a compound such as a biologically-active macromolecule, a nucleic acid or a peptide in particular, into a cell. The present invention also relates to said conjugate for delivery of a compound, such as a biologically-active macromolecule, a nucleic acid or a peptide, into a cell. The present invention further relates to a pharmaceutical composition comprising said conjugate and to its use. The present invention also relates to a method of delivering a compound to a cell or an organism, preferably a patient.

Abstract: This disclosure relates to vectors, isolated cells, compositions, and methods for the treatment of critical limb ischemia and associated disorders. One aspect of the disclosure relates to a vector comprising a nucleic acid encoding a 165A isoform VEGF protein and a promoter that regulates expression of the nucleic acid encoding the VEGF.

Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Abstract: The invention relates to double-stranded ribonucleic acids (dsRNAs) targeting gene expression of phosphatidylinositol 4-kinase (PI4K), in particular human phosphatidylinositol 4-kinase, catalytic, beta polypeptide (PIK4CB) or human phosphatidylinositol 4-kinase, catalytic, alpha polypeptide (PIK4CA), and their use for treating infection by positive stranded RNA viruses such as hepatitis C virus (HCV). Each dsRNA comprises an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PIK4CB or PIK4CA target mRNA. A plurality of such dsRNA may be employed to provide therapeutic benefit. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier, and including a delivery modality such as fully encapsulated liposomes or lipid complexes.

Abstract: The present invention relates to a composition for promoting differentiation of pluripotent stem cells into cardiac muscle cells, and a method for inducing differentiation of pluripotent stem cells into cardiac muscle cells and a method for preparing cardiac muscle cells.

Abstract: The present disclosure provides synthetic substrates for long-term culture of stem cells; and methods of use of the synthetic substrates.

Abstract: In a culture method of the present invention, by culturing bone marrow stromal cells or mesenchymal stem cells under a pseudo micro-gravity environment generated by multi-axis rotation, bone marrow stromal cells or mesenchymal stem cells having an average cell size smaller than that before the culture are obtained. The bone marrow stromal cells or mesenchymal stem cells thus cultured are suitable as graft cells for a central nerve diseases therapy.

Abstract: The present invention concerns constructs based on sequences derived from the partitioning system of plasmid and chromosomal DNA of bacteria, such as eukaryotic expression vectors, fusion proteins and polynucleotides encoding the same and also eukaryotic cells transformed with or expressing such constructs. The present invention also concerns the use thereof in the regulation of gene expression and/or in the detection and control of the dynamics, localization or metabolism of genomic DNA loci of interest in eukaryotic cells.

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

Abstract: Provided is a polynucleotide encoding a protein having an activity to transfer a sugar to the hydroxy groups at the 4?- and 7-positions of a flavone.

Abstract: We disclose a particle comprising a matrix coated thereon and having a positive charge, the particle being of a size to allow aggregation of primate or human stem cells attached thereto. The particle may comprise a substantially elongate, cylindrical or rod shaped particle having a longest dimension of between 50 ?m and 400 ?m, such as about 200 ?m. It may have a cross sectional dimension of between 20 ?m and 30 ?m. The particle may comprise a substantially compact or spherical shaped particle having a size of between about 20 ?m and about 120 ?m, for example about 65 ?m. We also disclose a method of propagating primate or human stem cells, the method comprising: providing first and second primate or human stem cells attached to first and second respective particles, allowing the first primate or human stem cell to contact the second primate or human stem cell to form an aggregate of cells and culturing the aggregate to propagate the primate or human stem cells for at least one passage.

Abstract: Methods for producing compositions of decellularized extracellular matrix (DM) tissue culture are described. The compositions can be used for coating supports such as tissue culture substrates, osteogenic gels, and medical devices.

Abstract: The present invention relates to a method for the production of differentiated respiratory epithelial cells comprising: (a) providing a cell population comprising or consisting of precursor cells of respiratory epithelial cells; (b) culturing the cell population of (a) in culture medium to which keratinocyte growth factor has been added; wherein the cultured cell population is supplemented with a glucocorticoid, a cAMP analogue and a cAMP elevating agent and wherein said supplementation is either simultaneously with the addition of keratinocyte growth factor in step (b) or prior or subsequently to the addition of keratinocyte growth factor in step (b), thereby differentiating said precursor cells into respiratory epithelial cells.

Abstract: Pharmaceutical compositions and methods for inhibiting cell growth, modulating function of PCNA, treating prostate cancer, and enhancing PCNA trimer formation are disclosed.

Abstract: The invention relates to methods of selecting a cardiomyocyte from a cell population derived from a whole heart or a differentiated cell population derived from a stem cell without genetic alteration. Specifically, the invention relates to a method of selecting a cardiomyocyte from a cardiomyocyte-containing cell mixture without genetic alteration of a cardiomyocyte, on the basis of a relative content of cellular mitochondria and/or a relative mitochondrial transmembrane potential of the cell. The invention also relates to methods of enriching a cardiomyocyte from a cardiomyocyte-containing cell mixture without genetic alteration of a cardiomyocyte, producing a cardiomyocyte without genetic alteration of a cardiomyocyte, and evaluating the ratio of a cardiomyocyte in a cardiomyocyte-containing cell mixture.

Abstract: The present invention provides compositions and methods for the culture and maintenance of pluripotent stem cells. More particularly, the present invention provides for compositions and methods for culturing, maintaining, growing and stabilizing primate pluripotent stem cells in a feeder-free defined media further comprising human serum, or a soluble attachment component of the human serum, for promoting cell attachment.

Abstract: Disclosed are isolated mutant erythropoietin (EPO) polypeptides, functional fragment thereof, nucleic acid encoding such peptides, vectors including such nucleic acids and compositions including such peptides and nucleic acids. The mutant EPO peptides are unique in that they include a substitution at amino acid position number 76, such as a glutamic acid for arginine substitution at position 76. This substitution inhibits erythropoietic activity while retaining their neuroprotection. Also disclosed are methods of treating or inhibiting neuronal degeneration, reducing or inhibiting one or more symptoms associated with neuronal degeneration and/or glaucoma in a subject. The methods include administering a therapeutically effective amount of a isolated mutant erythropoietin EPO polypeptide, an expression vector encoding such a mutant erythropoietin EPO polypeptide, a viral particle including an expression vector, or a composition, thereby treating or inhibiting neuronal degeneration in the subject.

Abstract: The present invention relates to recombinant mussel adhesive protein wherein a DOPA residue is in vivo incorporated instead of a tyrosine residue, and a method for producing the same. More specifically, the present invention relates to recombinant mussel adhesive protein wherein a DOPA residue is incorporated instead of a tyrosine residue, and a method for producing the same, and a transformant for producing the recombinant mussel adhesive protein.

Abstract: Culture media comprising manganese and methods of culturing cells to improve sialylation and glycosylation of glycoproteins are provided.

Abstract: Generally, compositions and methods for handling processed sperm populations including samples that are freshly collected, transported as fresh samples, as well as samples that are frozen and thawed, those sorted into one or more subpopulations, and those that are otherwise processed or handled that impose trauma on the sperm cell. Such trauma can reduce the motility, fertility, viability and overall integrity of the sperm and reduce the sperm's ability to fertilize an egg, grow into a healthy embryo and produce a healthy offspring. The novel compounds described can be added to the sperm cell sample to reduce the traumatic effects of physical stress during mild as well as extensive sperm cell processing, methods of using the compounds in standard sperm processing procedures, the end products made from these methods including sperm and embryos, as well as methods of using those end products in assisted reproductive biology techniques in animals.

Abstract: Two vIRF4 (Kaposi's-sarcoma-associated-herpesvirus vIRF4) peptides, vif1, corresponding to aa202-216 of vIRF4, and vif2, corresponding to aa220-236 of vIRF4, are potent and selective HAUSP antagonists. The vif1 and vif2 peptides robustly suppress HAUSP DUB enzymatic activity, ultimately leading to p53-mediated anti-cancer activity. The vif1 and vif2 peptides, along with their homologues, are useful in treating cancer through regulation of p53 activity in a cancer cell. Also disclosed is the crystalline structure of vIRF4-HAUSP TRAF domain complex. The structure is useful in computer aided drug design for identifying an agent that interacts with and inhibits HAUSP, resulting in p53 medicated cell cycle arrest of cancer cells.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the PCSK9 gene (PCSK9 gene), comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PCSK9 gene.

Abstract: The present invention describes material and methods related to synthetic peptides which block the secretion of neurotransmitters and induce muscle relaxation, and use of said peptides as inhibitors of neurotransmitter secretion and muscle contraction, and as inducers of muscle relaxation.

Abstract: The present application relates to a system for designing promoters for selective expression of genes. Thereby identified transcription regulatory elements are selected according to a specific methodology and used to create a library of transcription regulatory elements, which are then used to construct specific promoters, especially tissue-specific promoters.

Abstract: A method, called GETWISE, for targeting mouse genes is described. GETWISE is designed to increase the frequency of homologous recombination, facilitate screening, widen the applicability of engineered animals and circumvent intrinsic gene targeting problems. GETWISE utilizes the principle of modulating gene expression by targeting tetracycline-responsive elements into a specific locus. In GETWISE alleles, control of gene expression is transferred from the endogenous to a tetracycline-inducible promoter. Endogenous promoters now control expression of the reporter gene luciferase. Breeding of GETWISE carriers with tTA/rtTA carriers enables investigators to modulate gene expression in a ubiquitous or tissue-specific manner, depending on the presence of doxycycline. GETWISE enables the study of loss or gain of gene expression in any tissue of choice within a single mouse strain. GETWISE enables the analysis of the gene expression pattern with the luciferase assay.

Abstract: Provided herein is a synthetic or isolated polynucleotide encoding a mammalian 18S rRNA that is resistant to pactamycin. The pactamycin-resistance is conferred by one or more single residue substitutions in the 18S rRNA sequence; a fragment thereof harboring said substitutions; a complementary sequence thereto; or a substantially identical sequence of the foregoing. Related systems, methods and kits are also described.

Abstract: Methods for obtaining pluripotent (embryonic stem) cells from parthenogenetic embryos, especially primates, are provided. These cells are useful for producing differentiated cells, tissues and organs, especially human and non-human primate cells, tissues and organs.

Abstract: This invention relates to a cell comprising a reporter gene under control of an ARIA gene promoter, the cell being used for searching for an agent for prevention or treatment of diseases attributed to reduced insulin sensitivity, for searching for an obesity-controlling substance, or for searching for an obesity-inducing substance.

Abstract: The invention provides isolated Pre-Ligand Assembly Domain (PLAD) polypeptides which inhibit multimerization of a receptor complex comprising an IL-17R family member. Related PLAD-binding polypeptides, chimeric proteins, conjugates, nucleic acids, vectors, host cells, and methods are provided herein.

Abstract: The present invention provides muscle-derived progenitor cells that show long-term survival following transplantation into body tissues and which can augment soft tissue following introduction (e.g. via injection, transplantation, or implantation) into a site of soft tissue. Also provided are methods of isolating muscle-derived progenitor cells, and methods of genetically modifying the cells for gene transfer therapy. The invention further provides methods of using compositions comprising muscle-derived progenitor cells for the augmentation and bulking of mammalian, including human, soft tissues in the treatment of various cosmetic or functional conditions, including malformation, injury, weakness, disease, or dysfunction. In particular, the present invention provides treatments and amelioration for dermatological conditions, gastroesophageal reflux, vesico-ureteral reflux, urinary incontinence, fecal incontinence, heart failure, and myocardial infarction.

Abstract: The present invention provides a method of extracting and recovering embryonic-like stem cells, including, but not limited to pluripotent or multipotent stem cells, from an exsanguinated human placenta. A placenta is treated to remove residual umbilical cord blood by perfusing an exsanguinated placenta, preferably with an anticoagulant solution, to flush out residual cells. The residual cells and perfusion liquid from the exsanguinated placenta are collected, and the embryonic-like stem cells are separated from the residual cells and perfusion liquid. The invention also provides a method of utilizing the isolated and perfused placenta as a bioreactor in which to propagate endogenous cells, including, but not limited to, embryonic-like stem cells. The invention also provides methods for propagation of exogenous cells in a placental bioreactor and collecting the propagated exogenous cells and bioactive molecules therefrom.

Abstract: Tissues produced by culture of cells produced by nuclear transfer on a matrix derived from nuclear transfer embryos or embryos and pluripotent cells provided by other methods are provided. These tissues are useful for cell therapy.

Abstract: A subpopulation of cancer stem cells expressing elevated levels of uPAR have been identified among a population of cancer cells. Methods are provided for treating proliferative disorders such as cancer by administering one or more uPAR inhibitors. Methods are likewise provided for predicting the likelihood of recurrence of a cancer, preventing recurrence of a cancer, and identifying the likelihood of a cancer to respond to a particular cancer therapy.

Abstract: An IVF system for successfully utilizing spermatozoa separated into X-chromosome bearing and into Y-chromosome bearing population for insemination. The IVF system includes fertilization medium that can shorten the time from insemination to cleavage and a portable incubator for the transportation of maturing oocytes and inseminated oocytes comprising a straw (19) and an incubation element (20) that can be sealed with a cap (22).

Abstract: Disclosed herein are flowable tissue matrix compositions comprising small pieces of partially or completely decellularized tissue suspended in a gelatinized tissue or gelatin gel comprising partially or completely decellularized tissue or synthetic gelatin. The flowable tissue matrix compositions can contain factors that promote or enhance native cell migration, proliferation, and/or revascularization after implantation into a subject. Also disclosed are methods of making and using the flowable tissue matrix compositions. The compositions can be implanted into a tissue in need of repair, regeneration, healing, treatment, and/or alteration, and can promote or enhance native cell migration, proliferation, and/or revascularization.

Abstract: The present invention relates to compositions and methods for inhibiting or suppressing undifferentiated or pluripotent stem cell growth and proliferation in a differentiated or differentiating cell population or culture.

Abstract: Synthetic surfaces suitable for culturing stem cell derived cardiomyocytes contain acrylate polymers formed from one or more acrylate monomers. The acrylate surfaces, in many cases, are suitable for culturing stem cell derived cardiomyocytes in chemically defined media.

Abstract: This disclosure provides a newly developed strategy and particular options for differentiating pluripotent stem cells into cells of the hepatocyte lineage. Many of the protocols are based on a strategy in which the cells are first differentiated into early germ layer cells, then into hepatocyte precursors, and then into mature cells. The cells obtained have morphological features and phenotypic markers characteristic of human adult hepatocytes. They also show evidence of cytochrome p450 enzyme activity, validating their utility for commercial applications such as drug screening, or use in the manufacture of medicaments and medical devices for clinical therapy.

Abstract: The present invention provides a method of extracting and recovering embryonic-like stem cells, including, but not limited to pluripotent or multipotent stem cells, from an exsanguinated human placenta. A placenta is treated to remove residual umbilical cord blood by perfusing an exsanguinated placenta, preferably with an anticoagulant solution, to flush out residual cells. The residual cells and perfusion liquid from the exsanguinated placenta are collected, and the embryonic-like stem cells are separated from the residual cells and perfusion liquid. The invention also provides a method of utilizing the isolated and perfused placenta as a bioreactor in which to propagate endogenous cells, including, but not limited to, embryonic-like stem cells. The invention also provides methods for propagation of exogenous cells in a placental bioreactor and collecting the propagated exogenous cells and bioactive molecules therefrom.

Abstract: Provided herein are methods of isolating and expanding a plurality of multipotent stem cells. Also described are methods of expanding stem cells on a substrate comprising an HC-HA complex. Also described are isolated and expanded stem cells produced by the methods and uses thereof, including stem cell therapy, as niche cells for supporting other types of stem cells, or as bioreactors for the production of HC-HA complexes. Also described are uses of HC-HA complexes as a carrier for stem cells.

Abstract: The invention provides a method for increasing the stability and/or activity of a polypeptide at low pH and/or elevated temperatures. The invention further provides a method for increasing the melting temperature of a polypeptide. Also provided are paleoenzymologically reconstructed thioredoxin polypeptides having activity at higher temperatures and/or lower pH than extant thioredoxin polypepetides, as well as paleoenzymologically reconstructed thioredoxin polypeptides having higher melting temperatures than extant thioredoxin polypepetides.

Abstract: The present invention relates to methods for removing antigens from tissues by sequentially destabilizing and/or depolymerizing cytoskeletal components and removing and/or reducing water-soluble antigens and lipid-soluble antigens. The invention further relates to tissue scaffolding and decellularized extracellular matrix produced by such methods.

Abstract: The invention relates to the identification of genetic products that are expressed in association with a tumor and the nucleic acid coding therefor. The invention relates to the therapy and diagnosis of diseases in which the genetic products that are expressed in association with a tumor are expressed in an aberrant manner. The invention also relates to proteins, polypeptides, and peptides which are expressed in association with a tumor and the nucleic acids coding therefor.

Abstract: Previous methods for culturing primate pluripotent stem cells have required either fibroblast feeder cells or a medium which was exposed to fibroblast feeder cells to maintain the stem cells in an undifferentiated state. It has now been found that high levels of fibroblast growth factor in a medium together with at least one of gamma aminobutyric acid, pipecolic acid, and lithium, enables pluripotent stem cells to remain undifferentiated indefinitely through multiple passages, even without feeder cells or conditioned medium. Without beta-mercaptoethanol, the medium improves cloning efficiency. Also, a matrix of human proteins can be used to culture the undifferentiated cells without exposing the cells to animal products. Further disclosed are new primate pluripotent cell lines made using the defined culture conditions, including the medium and the matrix. Such new cell lines will have never been exposed to animal cells, animal products, feeder cells or conditioned medium.