Abstract: The present disclosure relates generally to models and methods to modulate neuronal network activities simulating normal brain functions or neurological disorders in culture by applying alternating electric field. The electric field has alternating polarity and changing frequencies to achieve neuronal synchrony. The present disclosure also provides method of modulating modulate directed growth of neuronal axon by applying an alternating field electrical signal. The present disclosure also provides methods of screening compounds using the disclosed models, kits and systems thereof.

Abstract: The present invention provides a method for inducing differentiation of pluripotent stem cells into neural precursor cells, comprising culturing the pluripotent stem cells in the presence of a small, molecule BMP inhibitor, and induced neural precursor cells prepared by this method.

Abstract: Methods of enhancing fertility of a female subject by increasing the number of oogonia present in the ovary of the female subject are provided. Aspects of the methods include methods of in vivo expansion of oogonia as well as methods of ex vivo expansion of oogonia.

Abstract: Factors for extending the ability of isolated pluripotent stem cells to generate extraembryonic lineages in vivo, following in vitro culture, herein, chemical extenders of pluripotency (CEP). Methods of extending the ability of a pluripotent cell to generate embryonic and extraembryonic lineages. The cell to be reprogrammed is contacted with effective amounts of the CEPs for a sufficient period of time to reprogram the cell into a chemically induced extended pluripotent cell (ciEPSC). ciEPSC are identified as an extended pluripotent cell based on properties including: (i) morphologically and (ii) functionally for example, based on their ability contribute to both TE and ICM, in vivo. The ciEPSCs can be cultured or induced to differentiate into cells of a desired type, and used in a number of applications, including but not limited to cell therapy and tissue engineering.

Abstract: An object of the present invention is to provide a method for generating an osteoblast that is applicable to repair of a bone defect due to various tumors, injuries, surgeries, etc. and to treatment for bone resorption typified by a periodontal disease, bone fracture, osteoporosis, etc., and that has a low risk of carcinogenesis. Provided as a means for achieving this object is a method for generating an osteoblast from a somatic cell of a mammal, the method comprising introducing Oct9 gene or an expression product thereof into the somatic cell.

Abstract: A lighting device includes a light guide plate, a light source circuit, and a chassis. By conducting an extrusion process, the light guide plate may at least include a first light-guiding area and a second light-guiding area. The light source circuit faces toward an inlet of the light guide plate. When the light source circuit emits light beams toward the light guide plate, the first light-guiding area reflects the light beams toward a first light-guiding angle group, and the second light-guiding area reflects the light beams toward a second light-guiding angle group. The first light-guiding angle group is different from the second light-guiding angle group. The chassis is configured to fix the light guide plate and the light source circuit.

Abstract: The present invention relates to a retinal pigment epithelial stem cell isolated from a posterior region of the retinal pigment epithelium of an adult mammal. The invention also relates to a method of inducing differentiation of retinal epithelial stem and progenitor cells in vitro, wherein the cells of the invention are highly plastic, multipotential stem cells. The invention also includes methods for the treatment of retinal diseases and vision loss involving the transplantation of retinal pigment epithelial stem cells or cells differentiated from retinal pigment epithelial stem cells to the retina of a patient in need of treatment.

Abstract: A genetically modified mouse is provided that comprises a conditional Acvr1 allele that comprises a mutated exon that, upon induction, converts to a mutant exon phenotype, wherein the mutant exon phenotype includes ectopic bone formation. Mice comprising a mutant Acvr1 exon 5 in antisense orientation, flanked by site-specific recombinase recognition sites, are provided, wherein the mice further comprise a site-specific recombinase that recognizes the site-specific recombinase recognitions sites, wherein the recombinase is induced upon exposure of the mouse to tamoxifen. Upon exposure to tamoxifen, the recombinase is expressed and acts on the RRS-flanked mutant exon 5 and places the mutant exon 5 in sense orientation and deletes the wild-type exon.

Abstract: The present invention relates to methods for generating mammalian multilineage-potential cells, including mesenchymal stem cells, comprising contacting mammalian somatic cells exhibiting a mature phenotype with PDGF-AB or functional derivative, fragment or mimetic thereof and Azacitidine or functional derivative or analog thereof for a time and under conditions sufficient to induce the transition of the somatic cells to cells exhibiting multilineage differentiative potential. Also provided are uses of said multilineage-potential cells, such as in promoting tissue repair and regeneration.

Abstract: [Problem] To provide a cell culture substrate, and a cell culturing method using the substrate and a method for inducing differentiation of pluripotent stem cells using the substrate, which allow culturing of pluripotent stem cells and allow differentiation of pluripotent stem cells into a specified cell species, particularly neural and neural progenitor cells, at a high purity. [Means for Solution] A cell culture substrate, characterized in that, onto the surface, one or more selected from the group consisting of N-cadherin, a fusion protein comprising an entire or partial region of N-cadherin, and a fusion protein comprising an entire or partial region of a protein homologous to N-cadherin are immobilized or coated.

Abstract: Disclosed herein are methods and compositions for targeted deletion of double-stranded DNA. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain, and polynucleotides encoding same. Methods for targeted deletion include introduction of such fusion proteins, or polynucleotides encoding same, into a cell such that two targeted cleavage events occur. Subsequent cellular repair mechanisms result in deletion of sequences between the two cleavage sites.

Abstract: The present invention provides for methods, compositions, and kits for producing an induced pluripotent stem cell from a non-pluripotent mammalian cell using a 3?-phosphoinositide-dependent kinase-1 (PDK1) activator or a compound that promotes glycolytic metabolism as well as other small molecules.

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 a novel ecdysone receptor/chimeric retinoid X receptor-based inducible gene expression system and methods of modulating gene expression 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 invention provides for compositions and methods for identifying and validating modulators of cell fate, such as such as maintenance, cell specification, cell determination, induction of stem cell fate, cell differentiation, cell dedifferentiation, and cell trans-differentiation. The invention relates to reporter nucleic acid constructs, host cells comprising such constructs, and methods using such cells and constructs. The invention relates to methods for making cells comprising one or more reporter nucleic acid constructs using fluorogenic oligonucleotides. The methods relate to high throughput screens.

Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.

Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized a proliferation-inducing ligand gene. Non-human animals and cells that express a human or humanized a proliferation-inducing ligand protein from an endogenous a proliferation-inducing ligand locus are described.

Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.

Abstract: This invention relates to a method for producing a protein of interest, comprising introducing a protein expression vector which comprises a gene fragment a gene fragment comprising a DNA encoding a protein of interest and a selectable marker gene and transposon sequences at both terminals of the gene fragment, into a suspension mammalian cell; integrating the gene fragment inserted between a pair of the transposon sequences, into a chromosome of the mammalian cell to obtain a mammalian cell capable of expressing the protein of interest; and suspension-culturing the mammalian cell; and a suspension mammalian cell capable of expressing the protein of interest.

Abstract: Disclosed herein are compositions and methods for sequencing, analyzing, and utilizing samples such as single samples. Also disclosed herein are compositions and methods for matching together two or more sequences from a sample. Also disclosed herein are compositions and methods for expressing and screening molecules of interest.

Abstract: The present invention provides a method of expressing at least one heterologous nucleic acid sequence in a cell, the method comprising introducing at least one heterologous nucleic acid sequence into a cell by infecting said cell with a recombinant negative-strand RNA virus vector comprising said at least one heterologous nucleic acid sequence, wherein the recombinant negative-strand RNA virus vector includes a viral genome coding for a mutated P protein, which leads to a loss of the viral genome replication ability without a loss of the viral transcription ability, and wherein said at least one heterologous nucleic acid sequence encodes a cellular reprogramming or programming factor or a therapeutic protein. In addition, the present invention provides a cell or a population of cells prepared in vitro by said method as well as a pharmaceutical composition comprising said cell or population of cells.

Abstract: Methods for de-differentiating or altering the life-span of desired “recipient” cells, e.g., human somatic cells, by the introduction of cytoplasm from a more primitive, less differentiated cell type, e.g., oocyte or blastomere are provided. These methods can be used to produce embryonic stem cells and to increase the efficiency of gene therapy by allowing for desired cells to be subjected to multiple genetic modifications without becoming senescent. Such cytoplasm may be fractionated and/or subjected to subtractive hybridization and the active materials (sufficient for de-differentiation) identified and produced by recombinant methods.

Abstract: Devices, systems, and methods for continuous cell culture and other reactions are generally described. In some embodiments, chambers (e.g., cell growth chambers) including at least a portion of a wall formed of a flexible member are provided. A retaining structure can be incorporated outside and proximate to the chamber such that when liquid is added to the chamber, the flexible member is consistently and predictably deformed, and a consistent volume of liquid is added. The flexible member can be formed of, in some embodiments, a gas-permeable medium. In some embodiments, reaction chambers can be arranged in a fluidic loop, and a bypass channel can be used to introduce and/or extract fluid from the loop without affecting loop operation.

Abstract: Gene encoding human glucokinase mutant is provided. The gene has the nucleotide sequence chosen from the nucleotide sequence listed as SEQ ID NO:2 and the nucleotide sequence wherein the ORF region encodes the same amino acid sequence as the one encoded by ORF region (position 487 to 1884) of SEQ ID NO:2 and the rest of the region is same as the non-ORF region of SEQ ID NO:2. Human glucokinase mutant encoded by the gene, the recombinant vectors carrying the gene, the hosts comprising the vectors, pharmaceutical compositions thereof, uses thereof, and methods for treating and preventing diseases by using the same are provided. The human glucokinase mutant encoded by the gene has higher activity than that of the wild type human glucokinase, and thus provides a new way of controlling blood glucose and/or preventing and/or treating disturbance of carbohydrate metabolism, especially preventing and treating diabetes.

Abstract: Modified interleukin-12 (IL-12) p40 polypeptides are disclosed. The modified polypeptides have alterations in the IL-12p40 subunit to eliminate the protease site between positions Lys260 and Arg261. The modified IL-12p40 polypeptides according to the invention have improved stability compared to wild-type mature human IL-12p40 polypeptides.

Abstract: The present invention relates to a mutant human alpha-synuclein with increased toxicity compared to wild-type alpha-synuclein, or a homologue thereof, wherein the mutant alpha-synuclein or homologue thereof comprises at least one amino acid substitution selected from the group consisting of a substitution at the alanine at position 56 (A56), at the alanine at position 76 (A76), at the methionine at position 127 (M127) and/or at the valine at position 118 (V118), as defined in the claims. Further, the invention relates to a polynucleotide encoding the mutant alpha-synuclein or homologue thereof, or an expression vector comprising said polynucleotide, a cell comprising the polynucleotide or expression vector, as defined in the claims. Also, a non-human animal comprising the cell of the invention is provided, as defined in the claims. Finally, the invention provides methods for identifying a substance that prevents or reduces toxicity of alpha-synuclein, as defined in the claims.

Abstract: An in vitro model system that guides the development of microvasculature, recapitulating the detailed organization of both its cellular and a-cellular components is established. Use of electrostretched fibrin microfibers enables both endothelial layer organization and co-culture of supporting perivascular (mural) cells such as vascular smooth muscle cells and pericytes. The fiber curvature affects the circumferential deposition of endothelial-produced ECM independently of cellular organization and induces deposition of higher quantities of vascular ECM proteins. Further, a luminal multicellular microvascular structure is disclosed.

Abstract: The disclosure provides methods for increasing genome stability of an embryonic stem (ES) cell or induced pluripotent stem (iPS) cell, increasing telomere length in an ES or iPS cell, or both, for example by contacting an ES or iPS cell with an agent that increases expression of Zscan4 in the cell. Methods for increasing genome stability or increasing telomere length in a population of ES or iPS cells are provided, for example by selecting Zscan4+ ES or iPS cells from the population of ES or iPS cells (which can include both Zscan4+ and Zscan4? ES or iPS cells). Therapeutic methods of using ES or iPS cells expressing Zscan4 are also provided. Further provided are methods of treating cancer by administering a Zscan4 polynucleotide or Zscan4 polypeptide. Also provided are methods of inducing differentiation of isolated ES or iPS cells into germ cells.

Abstract: The present invention relates to the generation of anterior definitive endoderm (ADE) cells from embryonic stem cells and the differentiation of such cells to, for example, pancreatic or liver cells. The invention also relates to cell lines, cell culture methods, cells markers and the like and their potential uses in a variety of applications.

Abstract: A composition of a female germinal cell (egg) extract of pluricellular organisms in M-phase of the cell cycle, the extract being used 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: 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: Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRP? gene. Genetically modified mice are described, including mice that express a human or humanized SIRP? protein from an endogenous SIRP? locus.

Abstract: Genetically modified mice are provided that express human ? variable (hV?) sequences, including mice that express hV? sequences from an endogenous mouse ? light chain locus, mice that express hV? sequences from an endogenous mouse ? light chain locus, and mice that express hV? sequences from a transgene or an episome wherein the hV? sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human ? variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human ? variable sequences, including human antibodies, are provided.

Abstract: The present invention is related to a method to reduce peptide amidation activity in a given cell line, cell lines with reduced peptide amidation activity, and uses thereof.

Abstract: Analyte sensors, methods for producing and using analyte sensors, methods of detecting and/or measuring analyte activity, detecting pH change, and/or, controlling the concentration of an analyte in a system, are disclosed. Embodiments of the analyte sensors according to the disclosure can provide an accurate and convenient method for characterizing analyte activity, detecting pH change, controlling the concentration of an analyte in a system, and the like, in both in vivo and in vitro environments, in particular in living cell imaging.

Abstract: The invention provides improved adeno-associated virus (AAV) Factor VIII (FVIII) vectors, including AAV FVIII vectors that produce a functional Factor VIII polypeptide and AAV FVIII vectors with high expression activity.

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: The present invention provides a method for improving pancreatic function in a subject in need thereof, the method comprising administering to the subject STRO-1+ cells and/or progeny cells thereof and/or soluble factors derived therefrom. The method of the invention is useful for treating and/or preventing and/or delaying the onset or progression of a disorder resulting from or associated with pancreatic dysfunction, e.g., resulting from abnormal endocrine or exocrine function of the pancreas.

Abstract: The present invention relates to a one-vector expression system comprising a sequence encoding two polypeptides, such as tyrosine hydroxylase (TH) and GTP-cyclohydrolase 1 (GCH1). The two polypeptides can be should preferentially be expressed at a ratio between 3:1 and 15:1, such as between 3:1 and 7:1. The invention is useful in the treatment of catecholamine deficient disorders, such as dopamine deficient disorders including but not limited to Parkinson's Disease. Moreover, the present invention provides a method to deliver the vector construct in order to limit the increased production of the catecholamine to the cells in need thereof.

Abstract: Various embodiments of the present invention include compositions, materials and methods for maintaining and propagating mammalian mesenchymal stem cells in an undifferentiated state in the absence of feeder cells and applications of the same.

Abstract: The present invention provides embryonic stem cells obtainable from an embryo of an immunodeficient mouse which is deficient in both Rag2 and Jak3 genes by culture in the presence of a GSK3 inhibitor and an MEK inhibitor, as well as a transgenic mouse, which is created with the use of these embryonic stem cells.

Abstract: Provided herein are methods to generate and screen peptides that exhibit drug like stabilities in vitro and in vivo. By selecting for enzyme resistance, Applicants are able to derive peptides that are not only stable to a broad spectrum of proteases, but also stable to other drug processing enzymes such as cytochrome P450s. This approach provides a general method to the rapid development of highly stable peptides for therapeutic development and diagnosis. The peptides are further modified for oral bioavailability.

Abstract: The present invention is directed generally to eukaryotic host cells comprising artificial endosymbionts and methods of introducing artificial endosymbionts into eukaryotic host cells. The invention provides artificial endosymbionts that introduce a phenotype to host cells that is maintained in daughter cells. The invention additionally provides eukaryotic host cells containing magnetotactic bacteria.

Abstract: An inactive CRISPR/Cas system-based fusion protein and its applications in gene editing are disclosed. More particularly, chimeric fusion proteins including an inCas fused to a DNA modifying enzyme and methods of using the chimeric fusion proteins in gene editing are disclosed. The methods can be used to induce double-strand breaks and single-strand nicks in target DNAs, to generate gene disruptions, deletions, point mutations, gene replacements, insertions, inversions and other modifications of a genomic DNA within cells and organisms.

Abstract: The method of the invention provides for producing a heterologous protein in mammalian host cells having nucleic acid encoding Hepatitis B X protein and the heterologous protein, by growing mammalian host cells selected from the group consistng of HKB11, CHO, BHK21, C2C12, and HEK293 cells, by growing mammalian host cells in non-adherent suspension culture, or by growing mammalian host cells which contain nucleic acid providing exogenous X-box Binding Protein, XBP1s. The conditions should be such that HBx, exogenous XBP1s if present, and the heterologous protein are expressed by the mammalian cells. The invention includes compositions for carrying out the method.

Abstract: The present disclosure is directed to the development of compositions, such as extracellular matrices, and processes for using the same, that both maintain stem cells in vitro pluripotency and enable self-renewal. 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 their functional domains, in the absence of differentiation inhibitors or feeder cells, the embryonic stem cells proliferated and maintained their pluripotency.

Abstract: The various embodiments herein provide a method for derivation and long term establishment of ground state pluripotent embryonic stem cells. Further the embodiments herein provides a method to inhibit the ERK and TGF ? signalling pathways for long term maintenance of the embryonic stem cells. The R2i mouse embryonic stem (ES) cells are derived from 3.5 day blastocysts. The mouse ES cells are cultured in media containing R2i and 2i inhibitors of ERK and TGF ? pathways. The ES cells are subjected to in vitro and in vivo differentiation. The ES cells are subjected to RT-PCR and qRT-PCR, flow cytometry and karyotyping. The result reveals that the R2i maintains the ground state of ES cells and self renewal. Also R2i increases embryonic cleavage and clonal propagation of ES. Further R2i asserts genomic integrity and pluripotency of ES.

Abstract: Stromal stem cells are prospectively isolated from human bone marrow then expanded into clonal populations and cultured and used, the isolation being on the basis of expression of a cell surface marker, wherein the cell surface marker binds an antibody and wherein said antibody cross reacts with a cell surface marker found on mouse stromal stem cells or rat stromal stem cells, and optionally also on a cell of at least one other mammalian species selected from mouse, rat, horse, rabbit and pig cells. Useful stromal stem cell populations are positive for SDC2.

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 human Occludin protein is identified as an essential Hepatitis C Virus (HCV) cell entry factor. Occludin is shown to render murine and other non-human cells infectable with HCV and to be required for HCV-susceptibility of human cells. Associated methods for inhibiting HCV infection, transgenic animal models for HCV pathogenesis, methods of identifying compounds or agents that prevent or mitigate interaction of HCV with Occludin, and HCV inhibitory agents are also disclosed. Kits and cell culture compositions useful for identifying compounds or agents that prevent or mitigate interaction of HCV with Occludin are also provided.

Abstract: The present invention provides polypeptides having a composite amino acid sequence derived from a consensus sequence representing the capsid proteins of two or more circulating strains of a non-enveloped virus. In particular, the invention provides virus-like particles comprising at least one composite polypeptide. Such virus-like particles have antigenic epitopes of two or more circulating strains of a non-enveloped virus and produce an increase in antisera cross-reactivity to one or more circulating strains of the non-enveloped virus. Methods of making composite virus-like particles and vaccine formulations comprising composite virus-like particles are also disclosed.