Abstract: The invention provides an isolated, purified population of human cells comprising CD8+ T cells with reduced Cbl-b activity. The invention provides uses of such cells in methods for inducing or enhancing an anti-tumor immune response in a subject. These methods comprise: (a) providing a cell population, from a subject or from another source, which comprises CD8+ T cells, (b) reducing Cbl-b activity in the CD8+ T-cells, (c) administering the cells of step (b) to the subject. The invention provides methods for making CD8+ T cells that do not require stimulation through a co-receptor in order for the cell to become activated or proliferated in response to contact via its T cell receptor. Such methods are based upon reducing function of Cbl-b. The invention also provides methods for identifying agents which affect Cbl-b expression or activity.

Abstract: Chondrocytes are prepared from perichondrocytes. The present invention provides a cell derived from a perichondrial tissue, the cell being capable of differentiating into a chondrocyte. The present invention also provides a method of preparing the above-described cell and a composition comprising the same. A method of preparing a chondrocyte and a medium for use in the method are also provided.

Abstract: The technology described herein is directed to methods and devices that can be used to induce functional organ structures to form within an implantation device by implanting it in vivo within the body of a living animal, and allowing cells and tissues to impregnate the implantation device and establish normal microenvironmental architecture and tissue-tissue interfaces. Then the contained cells and tissues can be surgically removed intact and either transplanted into another animal or maintained ex vivo by perfusing it through one or more of the fluid channels with medium and/or gases necessary for cell survival.

Abstract: The present invention provides methods to promote the differentiation of pluripotent stem cells into insulin producing cells. In particular, the present invention provides a method to produce a population of cells, wherein greater than 80% of the cells in the population express markers characteristic of the definitive endoderm lineage.

Abstract: The present invention is directed towards methods of culturing non-keratinocyte epithelial cells, with the methods comprising culturing non-keratinocyte epithelial cells in the presence of feeder cells and a calcium-containing medium while inhibiting the activity of Rho kinase (ROCK) in the feeder cell, the non-keratinocyte epithelial cells or both during culturing.

Abstract: Described herein, inter alia, are methods and compositions useful for induced pluripotent stem cell reprogramming.

Abstract: This invention discloses a method of increasing production of virus-like particles comprising expressing an avian influenza matrix protein. The invention also comprises methods of making and using said VLPs.

Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds.

Abstract: The present invention relates to isolated polypeptides having peroxygenase activity, and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Abstract: Disclosed are DNA polymerases having increased reverse transcriptase efficiency relative to a corresponding, unmodified polymerase. The polymerases are useful in a variety of disclosed primer extension methods. Also disclosed are related compositions, including recombinant nucleic acids, vectors, and host cells, which are useful, e.g., for production of the DNA polymerases.

Abstract: Compositions that include polymerases with features for improving entry of nucleotide analogs into active site regions and for coordinating with the nucleotide analogs in the active site region are provided. Methods of making the polymerases and of using the polymerases in sequencing and DNA replication and amplification as well as kinetic models of polymerase activity and computer-implemented methods of using the models are also provided.

Abstract: The present invention relates to novel mutant thioesterase enzymes and naturally-occurring equivalents thereof, compositions made from such enzymes and uses of thioesterase enzymes. In particular, the present invention provides mutant thioesterase enzymes that have altered properties, for example, altered substrate specificity, altered activity, altered selectivity, and/or altered proportional yields in the product mixtures. The present invention also provides polynucleotides encoding such mutant thioesterase enzymes, and vectors and host cells comprising such polynucleotides. The invention further provides for novel uses of thioesterases in the production of various fatty acid derivatives, which are useful as, or as components of, industrial chemicals and fuels.

Abstract: The present invention relates to hybrid polypeptides having pullulanase activity, and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Abstract: Described herein are prostate specific membrane antigen (PSMA) binding conjugates that are useful for delivering therapeutic, diagnostic and imaging agents. Also described herein are pharmaceutical compositions containing them and methods of using the conjugates and compositions. Also described are processes for manufacture of the conjugates and the compositions containing them.

Abstract: Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

Abstract: Provided herein are recombinant microorganisms having two or more copies of a nucleic acid sequence encoding xylose isomerase, wherein the nucleic acid encoding the xylose isomerase is an exogenous nucleic acid. Optionally, the recombinant microorganisms include at least one nucleic acid sequence encoding a xylulose kinase and/or at least one nucleic acid sequence encoding a xylose transporter. The provided recombinant microorganisms are capable of growing on xylose as a carbon source.

Abstract: The invention is directed to an in vitro method for joining a first set of double-stranded (ds) DNA molecules. Small molecules acting as chaperone agents are identified that promote efficient and rapid assembly (that is, joining) of overlapping double-stranded DNA fragments.

Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.

Abstract: The present invention relates to compositions of virus-like particles for the introduction of RNA-interference (RNAi-) inducing molecules into eukaryotic cells and methods for the cell type-specific transduction of a plurality of eukaryotic cells with RNAi-inducing molecules. The present invention furthermore relates to methods for a diagnosis, prevention and/or treatment of diseases or disease states associated with an increased expression rate of at least one endogenous gene, and/or with the undesired expression of at least one endogenous gene and/or foreign nucleic acids, in particular viral nucleic acids.

Abstract: This invention relates to the treatment and prevention of Alzheimer's disease (AD), tangle-predominant dementia (TPD) and other diseases associated with abnormal tau expression, e.g., tauopathies, using the 3?untranslated region (UTR) of the tau messenger RNA (mRNA) as a target, specifically using microRNAs that regulate the expression of tau. This invention is also in the field of screening for, identifying, and diagnosing such diseases. Specifically, this invention provides biomarkers for these diseases in the form of microRNAs.

Abstract: Methods for treating a neurodegenerative disorder associated with aggregation of tau protein in the brain of a subject, comprising administering to the subject a therapeutically effective amount of one or more inhibitory nucleic acids targeting microRNA-26a, microRNA-26b, or both microRNA-26a and 26b.

Abstract: The present invention concerns the use of particular RNA sequences as a medicament. More precisely, it concerns the use of small nucleolar RNAs (snoRNAs) which the inventor has shown to be involved in the mechanisms of aging. The snoRNAs of the invention can be used in particular to increase the stress resistance of a subject and to fight against the harmful effects of aging, typically for preventing or treating a degenerative disease, a laminopathy, diabetes, obesity or a cancer and, more generally, to prolong the lifespan of a subject. The snoRNAs of the invention can also be used in the treatment of infertility. The invention further relates to vectors, cells, transgenic animals and compositions capable of expressing an snoRNA of the invention, and methods using any of the above products of the invention as a tool for identification of a molecule active in the prevention or treatment of a pathology, abnormality or disorder linked to a mechanism of aging.

Abstract: A novel class of pharmaceuticals which comprises a Locked Nucleic Acid (LNA) which can be used in antisense therapy. These novel oligonucleotides have improved antisense properties. The novel oligonucleotides are composed of at least one LNA selected from beta-D-thio/amino-LNA or alpha-L-oxy/thio/amino-LNA. The oligonucleotides comprising LNA may also include DNA and/or RNA nucleotides.

Abstract: The invention relates to antisense oligonucleotidic sequences (ODN) against Smad7 suitably modified, and their uses in medical field as therapeutic biological agents, in particular in the treatment of chronic inflammatory bowel disease, such as Crohn's disease and ulcerative colitis.

Abstract: The present invention is based, in part, on our studies of molecular pathways that include the deubiquitinase CYLD. Accordingly, the present invention features, inter alia, nucleic acid constructs that express CYLD or a biologically active variant thereof (e.g., a variant including the catalytic domain), nucleic acids that inhibit the expression of a negative regulator of CYLD (e.g., PDE4B or LNK2), nucleic acids that modulate the expression of downstream CYLD targets (e.g., Akt, by inhibiting or promoting the expression of the downstream target), compositions including one or more of these types of constructs (e.g., pharmaceutical compositions), kits including one or more of the compositions described herein and instructions for use, screening methods to identify therapeutic agents {e.g., anti-inflammatory agents) that upregulate CYLD, downregulate a negative regulatory of CYLD, or modulate (e.g., inhibit) a downstream CYLD target (e.g.

Abstract: A composition for reducing a level of senescence of a cell or subject, a method of reducing a level of senescence in a cell or subject by using the composition, and a method of preventing and treating symptoms or diseases related to or caused by senescence of a cell or subject.

Abstract: The invention relates to the field of medicinal research, cartilage physiology and diseases involving the degeneration of cartilage tissue. More specifically, the invention relates to methods and means for identifying compounds that inhibit catabolic processes in chondrocytes and that decrease the degradation of cartilage and/or ECM. The invention also relates to the compounds that are useful in the treatment of osteoarthritis. The invention also relates to targets, the modulation of which results in a decrease in the degradation of ECM and/or cartilage and decrease inflammation. In addition, the invention relates to compositions and methods for the use thereof in treating conditions that are characterized by the degradation of ECM and/or cartilage and inflammation.

Abstract: The invention relates to siRNA molecules and their use in methods and pharmaceutical compositions for inhibiting the expression of the PDK1 gene. The invention also relates to the use of said siRNAs molecules in the treatment and/or prevention of an eye condition characterized by increased expression and/or activity of PDK1 gene, preferably said eye condition is conjunctivitis and/or an ocular allergy such as seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis.

Abstract: The invention relates to a method for modification of a host cell at a target locus, which method comprises: providing a host cell comprising, at a first locus, at least two site-specific recombination sites and a nucleic acid having an essential function or encoding a product having an essential function; introducing into the host cell, at the target locus, a further nucleic acid having the essential function or encoding for a product having the essential function; and carrying out recombination at the first locus via the at least two site-specific recombination sites, so that the nucleic acid having an essential function or encoding a product having an essential function is rendered non-functional, thereby to modify the host cell at the target locus. The invention also relates to a cell obtainable by a method of the invention.

Abstract: The methods and compositions described herein relate to the delivery of polypeptides to a target cell, e.g. by utilizing engineered non-pathogenic bacteria comprising a type three secretion system (T3SS) and T3SS-compatible substrates. In one aspect, described herein are non-pathogenic microbial cells that have been engineered to express both a functional type three secretion system (T3SS) and at least one polypeptide that is compatible with the T3SS. Due to the wide variety of polypeptides that can be delivered to a target eukaryotic cell using the compositions and systems described herein, a commensurately wide variety of applications is contemplated, e.g. therapeutics and reprogramming.

Abstract: The present invention relates to a nucleic acid comprising a Lactococcus CRISPR repeat region and/or a Lactococcus CRISPR spacer region.

Abstract: The present invention provides methods and compositions related to modulating the resistance of a cell against a target nucleic acid or a transcription product thereof. In some preferred embodiments, the present invention provides compositions and methods for the use of one or more cas genes or proteins for modulating the resistance of a cell against a target nucleic acid or a transcription product thereof. In some embodiments, the present invention provides methods and compositions that find use in the development and use of strain combinations and starter culture rotations. In additional embodiments, the present invention provides methods for labelling and/or identifying bacteria. In some preferred embodiments, the present invention provides methods for the use of CRISPR loci to determine the potential virulence of a phage against a cell and the use of CRISPR-cas to modulate the genetic sequence of a phage for increased virulence level.

Abstract: A process for efficient expression of a foreign gene in a Bacillus host was developed by varying the length and nucleotide sequence in the spacer region between ribosomal binding sequence (RBS) and initiation codon (ATG) of the gene. Bacillus thuringiensis cry2Ac gene was selected as a model gene because it requires an upstream open reading frame designated as orf2 for its efficient expression and crystallization in a Bacillus host.

Abstract: Provided herein are exogenous terminator sequences for use in fungi cell transcriptional termination.

Abstract: The present invention provides for a method of producing one or more fatty acid derived dicarboxylic acids in a genetically modified host cell which does not naturally produce the one or more derived fatty acid derived dicarboxylic acids. The invention provides for the biosynthesis of dicarboxylic acid ranging in length from C3 to C26. The host cell can be further modified to increase fatty acid production or export of the desired fatty acid derived compound, and/or decrease fatty acid storage or metabolism.

Abstract: Compositions and methods are provided for the targeted integration of a polynucleotide sequence of interest into the genome of a plant or plant cell. The methods and compositions employ recognition sites for endonucleases and endonucleases in combination with site-specific recombination sites/recombinases to provide an effective system for establishing target sites within the genome of a plant, plant cell or seed. Once such target sites are established, a variety of methods can be employed to further modify the target sites such that they contain a variety of polynucleotides of interest.

Abstract: The invention provides novel recombinant DNA molecules and constructs useful for modulating gene expression in plants, plant cells, seeds, and progeny plants. Plant regulatory elements comprising sequences from the Ubq10 gene of C. lacryma-jobi, as well as variants and fragments thereof having gene regulatory activity, are provided. The invention also provides transgenic plants, plant cells, plant parts, seeds, and progeny plants comprising the recombinant DNA molecules of the invention, along with methods of their use.

Abstract: Compositions and methods for controlling pests are provided. The methods involve transforming organisms with a nucleic acid sequence encoding an insecticidal protein. In particular, the nucleic acid sequences are useful for preparing plants and microorganisms that possess insecticidal activity. Thus, transformed bacteria, plants, plant cells, plant tissues and seeds are provided. Compositions are insecticidal nucleic acids and proteins of bacterial species. The sequences find use in the construction of expression vectors for subsequent transformation into organisms of interest, as probes for the isolation of other homologous (or partially homologous) genes. The insecticidal proteins find use in controlling, inhibiting growth or killing lepidopteran, coleopteran, dipteran, fungal, hemipteran, and nematode pest populations and for producing compositions with insecticidal activity.

Abstract: Compositions for transient but prolonged exogenous mRNA expression through the use of the transcription system of negative strand RNA viruses, and methods of use thereof are disclosed. In some embodiments, the system contains only RNAs and does not include any DNA molecules. The compositions typically include an RNA template unit (rTeUn) that includes a virus regulatory sequences operably linked to a coding sequence of interest. The rTeUn is typically transfected to a host cell's cytoplasm in the presence of virus expression system proteins that mediate replication of the rTeUn and transcription of the transgene. The rTeUn RNA bonded to viral proteins exhibits high resistance to degradation, prolonged duration of expression, and is free of viral genes. The compositions can be used to reprogram cell. For example, the compositions and methods can be used to redirected lymphocytes to target cancer cells, or to dedifferentiate somatic cells into induce pluripotent stem cells.

Abstract: The present invention provides a method of preparing adult red blood cells from stem cells in vitro using certain transcription factors for use in medicine, transfusions and transplants. The invention also provides blood compositions with cells prepared by the method.

Abstract: The invention is directed to a replication-deficient adenoviral vector comprising a nucleic acid sequence encoding a human atonal homolog-1 (Hath1) protein operably linked to a human glial fibrillary acidic protein (GFAP) promoter. The invention also is directed to a composition and method utilizing the adenoviral vector to generate sensory cells in the inner ear of a human.

Abstract: There is provided a method for inserting a nucleic acid sequence that encodes a foreign peptide into a poxvirus genome, said method comprising: identifying in the poxvirus genome a poxvirus open reading frame wherein said open reading frame is characterized by an initial ATG start codon and wherein expression of said open reading frame is driven by an operably-linked poxvirus promoter located upstream of the open reading frame and wherein expression of said open reading frame provides a peptide that is non-essential to viability of the poxvirus; and inserting the nucleic acid sequence that encodes the foreign peptide at a position downstream of the poxvirus promoter; wherein following said insertion, (i) the nucleic acid that encodes the foreign peptide is operably-linked to the poxvirus promoter and expression of said nucleic acid is driven by said poxvirus promoter; and (ii) translation of the foreign peptide is initiated at an ATG start codon located at the same position as the ATG start codon of the poxvi

Abstract: Described herein are recombinant polynucleotide-binding polypeptides, recombinant fusion proteins made with the described polynucleotide-binding polypeptides, methods of using the described recombinant polynucleotide-binding polypeptides and recombinant fusion proteins to modify genomic DNA of cells and, in some embodiments, create recombinant cells. Methods are also provided herein for genetically modifying a neuronal stem cell. Methods are also provided for treating a neurological disorder in a subject that include the administration of genetically modified neuronal stem cells produced by the methods disclosed herein.

Abstract: The present invention provides methods and compositions for producing ?-phellandrene hydrocarbons from cyanobacteria.

Abstract: The invention provides a non-naturally occurring microbial organism having a 2-hydroxyisobutyric acid, 3-hydroxyisobutyric acid or methacrylic acid pathway. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in a 2-hydroxyisobutyric acid, 3-hydroxyisobutyric acid or methacrylic acid pathway. The invention additionally provides a method for producing 2-hydroxyisobutyric acid, 3-hydroxyisobutyric acid or methacrylic acid. The method can include culturing a 2-hydroxyisobutyric acid, 3-hydroxyisobutyric acid or methacrylic acid producing microbial organism expressing at least one exogenous nucleic acid encoding a 2-hydroxyisobutyric acid, 3-hydroxyisobutyric acid or methacrylic acid pathway enzyme in a sufficient amount and culturing under conditions and for a sufficient period of time to produce 2-hydroxyisobutyric acid, 3-hydroxyisobutyric acid or methacrylic acid.

Abstract: Modification of metabolic pathways includes genetically engineering at least one enzyme involved in elongating 2-ketoacids during leucine biosynthesis, and preferably at least isopropylmalate dehydrogenase or synthase (LeuB or LeuA in E. coli), to include at least such non-native enzyme, enzyme complex, or combination thereof to convert 2-ketobutyrate or 2-ketoisovalerate to a C7-C11 2-ketoacid, wherein the production of such is at a higher efficiency than if a purely native pathway is followed. The C7-C11 2-ketoacid may then be converted, via a native or genetically engineered thiamin dependent decarboxylase, to form a C6-C10 aldehyde having one less carbon than the C7-C11 2-ketoacid being converted. In some embodiments the C6-C10 aldehyde may then be converted via additional native or genetically engineered enzymes to form other C6-C10 products, including alcohols, carboxylic acids, and alkanes.

Abstract: The present invention relates to methods of synthesizing long-chain polyunsaturated fatty acids, especially eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, in recombinant cells such as yeast or plant cells. Also provided are recombinant cells or plants which produce long-chain polyunsaturated fatty acids. Furthermore, the present invention relates to a group of new enzymes which possess desatorase or elongase activity that can be used in methods of synthesizing long-chain polyunsaturated fatty acids.

Abstract: A biosynthetic method of making a capsaicinoid including expressing a first gene product of CS/AT3/Pun1 in a cellular system, growing the cellular system in a medium, and collecting the capsaicinoid. The biosynthetic method further includes expressing a second gene product of ACS1 and expressing a third gene product of pAMT in the cellular system.

Abstract: The present invention relates to microorganisms and polypeptides for detoxifying aldehydes associated with industrial fermentations. In particular, a heat-stable, NADPH- and iron-dependent alcohol dehydrogenase was cloned from Thermoanaerobacter pseudethanolicus 39E and displayed activity against a number of aldehydes including inhibitory compounds that are produced during the dilute-acid pretreatment process of lignocellulosic biomass before fermentation to biofuels. Methods to use the microorganisms and polypeptides of the invention for improved conversion of bio mass to biofuel are provided as well as use of the enzyme in metabolic engineering strategies for producing longer-chain alcohols from sugars using thermophilic, fermentative microorganisms.

Abstract: An object of the present invention is to provide a fermented product containing equol-producing microorganisms in the state of living cells by which equol production ability is maintained. When producing a fermented material by using an equol-producing microorganism, with soybean powder or soybean milk as raw materials, (1) preparing a mother starter by fermentation under anaerobic conditions by using an equol-producing microorganism in the presence of a daidzein species at pH 5.0 or higher, (2) preparing a bulk starter by fermentation under anaerobic conditions by using said mother starter in the presence of a daidzein species at pH 5.0 or higher, and (3) preparing a fermented material by fermentation by using said bulk starter in a medium containing soybean powder or soybean milk, enables production of a fermented material containing microorganisms in the state of living cells in which the equol production ability is maintained.