Abstract: The invention provides methods and compositions relating to differentiated cell populations that derive from pluripotent stem cells. The methods relate to reducing the number of residual stem cells present in such populations. The compositions include differentiated cell populations that contain reduced number of stem cells or that contain no stem cells. Pluripotent stem cells may be reduced in number and/or function through exposure to low oxygen levels.

Abstract: The present invention is related generally to embryonic-like stem cells isolated from human umbilical cord blood, designated herein as cord blood-stem cells (CB-SC's), which display the characteristics of embryonic stem cells and hematopoietic cells. These cells have the capability of proliferation and are able to differentiate to multiple types of cells. In addition, the CB-SC display low immunogenicity and immune regulation. These cells are, therefore, suitable for use in stem cell-based therapies for the treatment of diseases such as Parkinson's disease, diabetes, spinal cord damage, multiple sclerosis, cardiovascular disease, stroke and birth defects, and for preventing, treating and/or reducing an autoimmune disease in a mammalian subject.

Abstract: A method and system for collecting a double volume of red blood cells using a spinning membrane separator is provided by which a first quantity of whole blood is withdrawn from a donor; a first quantity of whole blood is flowed to the spinning membrane separator; where it is separated into a first quantity of red blood cells and a first quantity of plasma. The first quantity of red blood cells and the first quantity of plasma are then flowed to respective collection containers, and at least a portion of the first quantity of plasma is returned to the donor. A second quantity of whole blood withdrawn from the donor, and then separated into a second quantity of red blood cells and a second quantity of plasma using the spinning membrane separator. The second quantity of red blood cells and the second quantity of plasma are then flowed to the respective collection containers, and at least a portion of the second quantity of plasma is returned to the donor.

Abstract: Provided is a method for producing mesenchymal stem cells from human pluripotent stem cells, the method including: a) forming embryonic bodies from human pluripotent stem cells; b) attaching the embryonic bodies to a culture dish to induce natural differentiation of the embryonic bodies into mesenchymal stem cells; and c) performing continuous proliferative culturing of the mesenchymal stem cells while still maintaining the identity of the mesenchymal stem cells. Also, provided is a standardized method for inducing differentiation of mesenchymal stem cells, which can be broadly applied to all human pluripotent stem cells regardless of a difference in the genetic background thereof.

Abstract: The present disclosure provides methods of treating or preventing obesity or causing weight loss or treating or preventing metabolic syndrome comprising administering to a subject a population of cells enriched for STRO-1+ cells and/or progeny thereof and/or soluble factors derived therefrom.

Abstract: The present invention provides methods to promote the differentiation of pluripotent stem cells. In particular, the present invention provides methods to produce a population of cells, wherein greater than 10% of the cells in the population express markers characteristic of single hormonal pancreatic beta cells.

Abstract: The present invention provides methods to promote the differentiation of pluripotent stem cells. In particular, the present invention provides a method to increase the expression of markers associated with the pancreatic endocrine lineage.

Abstract: The invention is directed to methods for making cells in vitro that have an extra-embryonic endodermal precursor phenotype. The method involves culturing cells from blastocysts under specific defined conditions.

Abstract: The present inventors developed hepatitis C virus recombinants expressing NS5A from genotype 1a, 1b, 2a, 3a, 4a, 5a, 6a or 7a in the context of a genotype 2a backbone. Additional recombinants express NS5A and the structural proteins (Core, E1 and E2), p7 and NS2 from genotype 1a, 1b, 3a, 4a, 5a, 6a or 7a in the genotype 2a backbone. Sequence analysis of the recombinants recovered after viral passage in Huh7.5 cells revealed adaptive mutations in NS5A and/or NS3. The importance of these mutations for improved growth kinetics was shown in reverse genetic studies.

Abstract: A recombinant baculovirus is provided for preparing picornavirus virus-like particles (VLP), wherein Chitinase A (ChiA) and Cathepsin V (v-cath) genes of the recombinant baculovirus are functionally disrupted and the recombinant baculovirus includes a picornavirus capsid protein gene under control of a strong promoter, and includes a protease gene configured for encoding a protease for hydrolyzing the capsid protein under control of a weak promoter. The recombinant baculovirus of the present invention may adopt High Five or Sf-9 cells for manufacturing enterovirus virus-like particles with improved stability and higher yields in comparison with the conventional arts. A method for preparing virus like particles is also herein provided.

Abstract: The present disclosure relates to non-naturally occurring polypeptides useful for preparing Ezetimibe, polynucleotides encoding the polypeptides, and methods of using the polypeptides.

Abstract: Provided herein are polypeptides having ketol-acid reductoisomerase activity as well as microbial host cells comprising such polypeptides. Polypeptides provided herein may be used in biosynthetic pathways, including, but not limited to, isobutanol biosynthetic pathways.

Abstract: Compositions and methods for conferring hydroxyphenyl pyruvate dioxygenase (HPPD) herbicide resistance or tolerance to plants are provided. Compositions include amino acid sequences, and variants and fragments thereof, for mutant HPPD polypeptides. Nucleic acids that encode the mutant HPPD polypeptides are also provided. Methods for conferring herbicide resistance or tolerance, particularly resistance or tolerance to certain classes of herbicides that inhibit HPPD, in plants are further provided. Methods are also provided for selectively controlling weeds in a field at a crop locus and for the assay, characterization, identification and selection of the mutant HPPDs of the current invention that provide herbicide tolerance.

Abstract: The present invention relates to recombinant C. difficile toxin A (TcdA) and toxin B (TcdB) and binary toxin A (CDTa) proteins comprising specifically defined mutations relative to the native toxin sequence that substantially reduce or eliminate toxicity. The invention also relates to vaccines and immunogenic compositions comprising these recombinant toxins, as well as combinations of these toxins with binary toxin B (CDTb), which are capable of providing protection against C. difficile infection and/or the effects thereof. The invention also relates to methods of inducing an immune response to C. difficile comprising administering the vaccines and immunogenic compositions described herein to a patient. The invention also encompasses methods of expressing recombinant C. difficile toxin A and toxin B and CDTa mutants and CDTb in recombinant expression systems.

Abstract: The present disclosure provides engineered transaminase polypeptides for the production of amines, polynucleotides encoding the engineered transaminases, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases to prepare compounds useful in the production of active pharmaceutical agents.

Abstract: The present invention provides, among other things, chimeric DNA polymerases containing heterologous domains having sequences derived from at least two DNA polymerases that have at least one distinct functional characteristics (e.g., elongation rate, processivity, error rate or fidelity, salt tolerance or resistance) and methods of making and using the same. In some embodiments, the present invention can combine desired functional characteristics (e.g., high processivity; high elongation rate; thermostability; resistance to salt, PCR additives (e.g., PCR enhancers) and other impurities; and high fidelity) of different DNA polymerases in a chimeric polymerase.

Abstract: Recombinant gelonin polypeptides with decreased antigenicity are provided. Cell-targeted constructs comprising said recombinant gelonin polypeptides are also provided. Such constructs can be used in methods for targeted cell killing, such as for treatment of cell proliferative diseases (e.g., cancer).

Abstract: Embodiments of the invention include methods of altering the enzymatic activity or solubility of an extremophilic enzyme or post-translationally modifying a protein of interest via using isolated or partially purified glycosyltransferases and/or post-translational modification proteins, extracts of cells comprising glycosyltransferases and/or post-translational modification proteins, and/or in cells comprising one or more glycosyltransferases and/or post-translational modification proteins.

Abstract: Genes SWA2 and GAM1 from the yeast, Schwanniomyces occidentalis, encoding ?-amylase and glucoamylase, respectively, were cloned and expressed in H. polymorpha. The expression was achieved by integration of the SWA2 and GAM1 genes into the chromosome of H. polymorpha under operably linked to a strong constitutive promoter of the H. polymorpha-glyceraldehyde-3-phosphate dehydrogenase gene (HpGAP. Resulting transformants acquired the ability to grow on a minimal medium containing soluble starch as a sole carbon source and can produce Ethanol at high-temperature fermentation from starch up to 10 g/L. A XYN2 gene encoding endoxylanase was obtained from the fungus Trichoderma resee, and a xlnD gene coding for ?-xylosidase was obtained from the fungus Aspergillus niger. Co-expression of these genes was also achieved by integration into the H. polymorpha chromosome under control of the HpGAP promoter.

Abstract: The present invention relates to a composition having the activity of degrading the cell wall of a Mycobacterium species comprising: (a) a first fusion protein including (i) a domain with a first enzymatic activity, the enzymatic activity being at least one or more of the following: N-acetyl-b-D-muramidase (lysozyme, lytic transglycosylase), N-acetyl-b-D-glucosaminidase, N-acetylmuramoyl-L-alanine amidase, L-alanoyl-D-glutamate (LD) endopeptidase, c-D-glutamyl-meso-diaminopimelic acid (DL) peptidase, D-Ala-m-DAP (DD) endopeptidase, or m-DAP-m-DAP (LD) endopeptidase, (ii) at least one peptide stretch fused to the N- or C-terminus of the domain with the first enzymatic activity; and (iii) a protein transduction domain (PTD) being at the N- or C-terminus of the first fusion protein; and (b) a second fusion protein including (i) a domain with a second enzymatic activity, the enzymatic activity being at least one or more of the following: lipolytic activity, cutinase, mycolarabinogalactanesterase, or alpha/beta hy

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidoes 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: The present invention provides a method for increasing the yield of a protein produced by cultivating eukaryotic cells and adding an ionic substance to the culture medium prior to harvest of the protein. Suitable ionic substances are the salts of the Hofmeister series, amino acids and peptone.

Abstract: Improving wild nitrile hydratase enables the provision of a protein which has nitrile hydratase activity and which has further improved heat resistance, amide compound resistance and high temperature accumulation properties. Use protein (A) or (B), (A) being a protein characterized by having nitrile hydratase activity and by including an amino acid sequence in which a specific amino acid residue in an amino acid sequence in wild nitrile hydratase has been substituted by another amino acid residue, and (B) being a protein characterized by having nitrile hydratase activity and by including an amino acid sequence in which one or several amino acid residues in the amino acid sequence of protein (A), other than the abovementioned specific amino acid residue, is deleted, substituted and/or added.

Abstract: A method for the in vitro diagnosis of colorectal cancer that comprises determining the presence of the protein disulfide isomerase tumor marker in a biological sample taken from a patient suspected of having colorectal cancer using at least one anti-PDI monoclonal antibody directed against a PDI epitope chosen from the epitopes of sequence SEQ ID No.1, SEQ ID No.2, with an aromatic amino acid which is close in the three-dimensional structure of PDI and SEQ ID No.3.

Abstract: The present invention generally relates to subpopulations of mammalian cells with distinctive ribosome translational profiles, i.e. translational activities. The present invention further relates to methods for identifying and isolating such cells, kits comprising the same, or methods which utilize different translational activities of these subpopulations of mammalian cells.

Abstract: One aspect of the present invention relates to a reporter system for detection of protein-protein interactions in the periplasm of a prokaryotic host cell. The reporter system includes a first expression system which has a nucleic acid molecule encoding a first fragment of a reporter protein molecule, a nucleic acid molecule encoding a first signal sequence, and a nucleic acid molecule encoding a first member of a putative binding pair, where the nucleic acid molecule encoding the first fragment, the nucleic acid molecule encoding the first signal sequence, and the nucleic acid molecule encoding the first member of the putative binding pair are operatively coupled to permit their expression in a prokaryotic host cell as a first fusion protein.

Abstract: Disclosed are devices and methods to synthesize polynucleotides and libraries of polynucleotides such as libraries of oligonucleotides. In exemplary embodiments, the device includes a support having a plurality of features. Each feature contains a plurality of oligonucleotides. Within each feature, each of the plurality of oligonucleotides includes an identical predetermined subunit sequence of X nucleosides and a degenerate sequence of Y nucleosides. A predetermined combination of a subset of the features can be used to produce a polynucleotide having a predetermined sequence of Z nucleosides.

Abstract: The present invention relates to chemical modification motifs for oligonucleotides. The oligonucleotides of the present invention, such as chemically modified antisense oligonucleotides, can have increased in vivo efficacy. The chemically modified oligonucleotides provide advantages in one or more of potency, efficiency of delivery, target specificity, toxicity, and/or stability. The chemically modified oligonucleotides have a specific chemical modification motif or pattern of locked nucleic acids (LNAs). The oligonucleotide (e.g. antisense oligonucleotide) can target RNA, such as miRNA or mRNA. Also provided herein are compositions comprising the chemically modified oligonucleotides and methods of using the chemically modified oligonucleotides as therapeutics for various disorders, including cardiovascular disorders.

Abstract: The invention relates to identifying and evaluating target coding sequences for control of plant parasitic nematodes by inhibiting one or more biological functions, and their use. The invention provides methods and compositions for identification of such sequences and for the control of a plant-parasitic nematode population. By feeding one or more recombinant double stranded RNA molecules provided by the invention to the nematode, a reduction in disease may be obtained through suppression of nematode gene expression. The invention is also directed to methods for making transgenic plants that express the double stranded RNA molecules, and the plant cells and plants obtained thereby.

Abstract: The present invention is directed to nucleic acid molecules containing a loop sequence designed to circumvent exportin-5 mediated export, and methods using these novel molecules.

Abstract: The present invention refers to inhibitors of microRNAs, particularly of microRNAs miR-212 and/or miR-132 for use in medicine, particularly in the diagnosis, treatment or prevention of cardiac disorders, e.g. cardiac hypertrophy-associated or autophagic disorders, and further refers to isolated nucleic acid molecules, particularly microRNAs miR-212 and/or miR-132 and related sequences, for use in medicine, particularly human medicine, more particularly in the diagnosis, treatment or prevention of disorders involving cardiac atrophy and/or dysfunctional autophagy, e.g. cardiac cachexia.

Abstract: The present invention relates to methods, kits and compositions to treat hypertension and other cardiovascular diseases in a subject, in particular, a method of treating or preventing a cardiovascular disease in a subject comprising administering to a subject at least one anti-miR agent to miRNA-425. In some embodiments, an anti-miR agent is a small molecule or an oligonucleotide complementary to at least part of the miR-425 of SEQ ID NO: 1, or an anti-miR complementary to at least part of the miRNA seed sequence AUGACA (SEQ ID NO: 2). Another aspect of the present invention relates to methods, kits and compositions to treat low blood pressure in a subject comprising administering a composition comprising a miR-425 agent to decrease ANP levels in the subject.

Abstract: The present invention features methods for stimulating clearance of misfolded or aggregated proteins or peptides in microglia, and treating neurodegenerative diseases associated with such pathology in brain by selectively inhibiting the expression or activity of Acyl-CoA:Cholesterol Acyltransferase 1, but not Acyl-CoA:Cholesterol Acyltransferase 2.

Abstract: The present invention features methods for stimulating clearance of misfolded or aggregated proteins or peptides in microglia or neurons, and treating neurodegenerative diseases associated with such pathology in brain by selectively inhibiting the expression or activity of Acyl-CoA:Cholesterol Acyltransferase 1, but not Acyl-CoA:Cholesterol Acyltransferase 2.

Abstract: Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.

Abstract: Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.

Abstract: The present invention relates to a novel customized sRNA that reduces gene expression in prokaryotic cells, a preparation method thereof, and the use thereof, and more particularly to a synthetic sRNA comprising an Hfq binding site, derived from the sRNA of any one of MicC, SgrS and MicF, and a region that base-pairs with the target gene mRNA, and to a preparation method thereof and the use thereof. The synthetic sRNA according to the invention has an advantage in that the degree of inhibition of the target gene can be controlled by regulating the ability of the synthetic sRNA to bind to the mRNA of the target gene. The use of the synthetic sRNA that regulates the expression of the target gene makes it possible to effectively construct a recombinant microorganism without using a conventional gene deletion method and to reduce the expression of the target gene, and thus the synthetic sRNA is useful for the production of recombinant microorganisms.

Abstract: An aptamer-mRNA conjugate is provided. The aptamer-mRNA conjugate may include an aptamer component that binds a membrane associated protein on a target cell and an mRNA component that is expressed by the target cell.

Abstract: This invention relates to metabolically engineered microorganism strains, such as bacterial strains, in which there is an increased utilization of malonyl-CoA for production of a chemical product, which includes 3-hydroxypropionic acid.

Abstract: Alkynyl-derivatized cap analogs, alkynyl-modified capped RNA, 1,4-disubstituted triazole-derivatized capped RNA, methods of preparation, methods of isolation, and uses thereof are provided. The “click” modification facilitates detection and isolation of capped RNAs and the 1,4-disubstituted triazole derivatives formed by the “click” reaction are useful for producing RNA transcripts and encoded protein.

Abstract: The present invention concerns a method of producing a desired heterologous gene product wherein said heterologous gene product is expressed from a strong promoter, said method comprising expressing said gene using a mutant mRNA leader which comprises one or more mutations which enhance transcription of the gene. The invention also provides a mutant Pm mRNA leader sequence, and a vector and a library comprising the leader sequence. Methods of obtaining an mRNA mutant leader and identifying an mRNA mutant leader are encompassed, along with a vector for selection or identification of an mRNA leader mutant and a use thereof for screening.

Abstract: In planta consolidated bioprocessing has the advantages of decreasing biomass pretreatment costs, utilizing excess plant protein production capacity for enzyme production, and decreasing mass transfer resistance of enzyme diffusion to its substrate. However, in planta expression of cell wall degrading (CWD) enzymes often leads to detrimental plant phenotypes that impact crop yield. To provide in planta CWD enzyme activity without any adverse phenotype, a thermostable xylanase, XynB (EC 3.2.1.8), was engineered with a thermoregulated intein, Tth-HB27 DnaE-1 (Tth intein), that controls its hydrolytic activity through conditional intein splicing. Maize plants expressing the heat inducible Tth intein-modified XynB developed normally, yet possessed enhanced post harvest glucose production from dried corn stover. Expression of CWD enzymes as dormant, intein-modified proteins that can be activated by heat treatment after harvest provides the basis for developing a novel cellulosic processing trait in plants.

Abstract: The present invention relates generally to the field of molecular biology and concerns a method for enhancing yield-related traits in plants by modulating expression in a plant of a nucleic acid encoding an importin or a yield-related polypeptide. The present invention also concerns plants having modulated expression of a nucleic acid encoding an importin or a yield-related polypeptide, which plants have enhanced yield-related traits relative to corresponding wild type plants or other control plants. The invention also provides constructs useful in the methods of the invention.

Abstract: The soybean variety DLL1335 is disclosed. The invention relates to seeds, plants, plant cells, plant tissue, harvested products and soybean lint as well as to hybrid soybean plants and seeds obtained by repeatedly crossing plants of variety DLL1335 with other plants. The invention also relates to plants and varieties produced by the method of essential derivation from plants of DLL1335 and to plants of DLL1335 reproduced by vegetative methods, including but not limited to tissue culture of regenerable cells or tissue from DLL1335.

Abstract: The present invention relates generally the field of genetics, in particular methods, compositions and systems for controlling the inducible expression of transgenes, while eliminating background expression of transgene expression. The present invention relates to methods of use of the compositions and systems as disclosed herein for controlling the inducible expression of transgenes while eliminating background expression of transgene expression, such as use in, for example, the in generation of transgenic animals, use in therapeutic application and use in assays. In some embodiments, the present invention relates to a system of controlled expression of RNAi molecules which target binding sites in the untranslated regions of transgene, thereby the expression of the transgene is modulated and leakiness is reduced.

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

Abstract: A method for treating a renal disease in a subject is disclosed. The method includes administering into a kidney of the subject with an effective amount of a gutless adenoviral vector containing a polynucleotide encoding a therapeutic agent. The gutless adenoviral vector contains the nucleotide sequence of SEQ ID NO:13 or SEQ ID NO:15 and expresses the therapeutic agent in a kidney tissue of the subject.

Abstract: Certain embodiments are directed to Negevirus and their polynucleotides and polypeptides.

Abstract: The invention provides a method of propagating an adenoviral vector. The method comprises (a) providing a cell comprising a cellular genome comprising a nucleic acid sequence encoding a tetracycline operon repressor protein (tetR), and (b) contacting the cell with an adenoviral vector comprising a heterologous nucleic acid sequence encoding a toxic protein. The heterologous nucleic acid sequence is operably linked to a promoter and one or more tetracycline operon operator sequences (tetO), and expression of the heterologous nucleic acid sequence is inhibited in the presence of tetR, such that the adenoviral vector is propagated. The invention also provides a system comprising the aforementioned cell and adenoviral vector.

Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific recombination, using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.