Abstract: The present disclosure relates to various different types of variants in E. coli coding and noncoding regions leading to enhanced lysine production for, e.g., supplements and nutraceuticals.

Abstract: A culture medium for improving the development of bovine in vitro fertilized embryos and cloned embryos includes a SOF basal medium, progesterone, vitamin E, L-carnitine, FGF, corticosterone, citrulline, EGF, IGF and LIF.

Abstract: Disclosed herein are methods and compositions for producing a Wnt polypeptide under a serum-free condition. Also disclosed herein are methods of purifying the Wnt polypeptide from a serum-free condition.

Abstract: A collagen-fibronectin-based method enables the production of tumors of centimeter size with recognizable pathological traits. The method supports reproducing tumor heterogeneity with preinvasive and invasive phenotypes and stacking of tumor portions using a paper-scaffold with 80 ?m-punched holes for larger nodule creation and easy separation of tumor portions for analysis. Macrotumors are convenient for testing drug delivery and therapeutic tools that necessitate a minimum tumor size relevant to in vivo.

Abstract: The present invention relates to the field of stem cells. More specifically, the invention provides methods and compositions useful for forming three-dimensional human retinal tissue in vitro. In a specific embodiment, an in vitro method for differentiating hiPSCs into three-dimensional retinal tissue comprising functional photoreceptors comprises the steps of (a) culturing the hiPSCs to form aggregates; (b) transitioning the aggregates into a neural induction medium; (c) seeding the aggregates on to extracellular matrix coated cell culture substrates; (d) replacing NIM with a chemically-defined differentiation medium; (e) detaching NR domains; (f) culturing in suspension; and (g) adding animal serum or plasma component and retinoic acid.

Abstract: The present invention relates to extracellular vesicles (EVs) as a novel therapeutic approach to lysosomal storage disorders (LSD). More specifically, the invention relates to the use of various protein engineering strategies for improving loading of hard-to-load LSD-related proteins and targeting of the resultant EVs to tissues and organs of interest.

Abstract: This disclosure provides an improved system for culturing human embryonic stem cells. The cells are cultured in suspension so as to maximize the production capacity of the culture environment. The new culture system of this invention allows for bulk proliferation of hES cells in a more cost-effective manner, which facilitates commercial production of important products for use in human therapy.

Abstract: The present invention relates to a method for obtaining a spermatozoid cell population with improved fitness which comprises contacting the starting spermatozoid population with a binding agent recognizing the CD10 biomarker and isolating spermatozoids from the starting population which do not bind to said biomarker. The invention also relates to the spermatozoid cell population, which can be used to fertilize an ovum, and to the embryo obtained. The invention also relates to a method for determining the fitness of sperm for fertilization based on the percentage of the spermatozoid population not carrying the CD/10 biomarker.

Abstract: The bioink disclosed herein includes one or more cells, a carrier material, and microspheres. The microspheres can include one or more biodegradable polymers and one or more compounds, such as a morphogenic compound. The methods disclosed herein can include three-dimensional bioprinting. Additional methods disclosed herein include producing functional tissue.

Abstract: Described is the efficient and robust generation of oligodendrocyte progenitor cells (OPCs) and oligodendrocytes from pluripotent stem cells (PSCs). The protocols provided recapitulate the major steps of oligodendrocyte differentiation, from neural stem cells to OLIG2+ progenitors, and then to O4+ OPCs, in a significantly shorter time than the 120-150 days required by previous protocols. Furthermore, O4+ OPCs are able to differentiate into MBP+ mature oligodendrocytes in vitro, and to myelinate axons in vivo when injected into immuno-compromised Shiverer mice, providing proof of concept that transplantation of PSC-derived cells for remyelination is technically feasible.

Abstract: Herein is reported a method for the co-cultivation of single deposited B-cells, which can be of any source, with EL-4 B5 feeder cells in a suitable co-cultivation medium. In the herein reported methods the EL-4 B5 cells have been irradiated with a dose of less than 40 Gy, preferably 9.5 Gy or less. Thereby the EL-4 B5 cells have a higher viability and maintain the ability to divide in cultivation at doses less than 6 Gy.

Abstract: The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

Abstract: The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to an immunoresponsive cell comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)), and expressing increased level of IL-33. In certain embodiments, the engineered immunoresponsive cells are antigen-directed and have enhanced immune-activating properties.

Abstract: A method of generating cells of the T cell lineage is provided comprising (a) culturing a sample comprising stem cells or progenitor cells with a Notch ligand conjugated to a suspension support and (b) isolating cells of the T cell lineage. In one embodiment, the cells of the T-cell lineage are progenitor T cells or mature T cells. Compositions, kits and uses thereof are also provided.

Abstract: The present invention is directed to the use of microfluidics in the preparation of cells and compositions for therapeutic uses.

Abstract: The present invention relates to a method of culturing primitive macrophages from stem cells. Specifically, the method comprises contacting and incubating stem cells with a serum-free culture media comprising a GSK3 inhibitor to differentiate stem cells into cell of the mesoderm lineage, contacting and incubating cells of the mesoderm lineage with a culture media comprising DKK1 to differentiate the cells into the hematopoietic lineage, maturing the cells of the hematopoietic lineage and contacting and incubating these cells with a culture media comprising M-CSF to drive differentiation into primitive-like macrophages. The invention also relates to a primitive-like macrophage, use of the primitive-like macrophage and a kit when used in the method of the invention.

Abstract: Methods of differentiation of pluripotent stem cells into hematopoietic precursor cells, wherein the method is carried out under suspension agitation, and wherein a GSK-3-inhibitor or a Wnt pathway activator is added during a stage of mesoderm induction, and cell culture media for use in the methods, as well as kits for performing the same.

Abstract: This invention provides a method for preparing a brown adipocyte from a somatic cell of a mammal by introducing at least one brown adipocyte-related gene or expression product thereof and at least one reprogramming-related gene or expression product thereof into the somatic cell, the brown adipocyte-related gene being at least one member selected from the group consisting of PRDM16(P) and C/EBP?(C), the reprogramming-related gene being at least one member selected from the group consisting of Myc family genes (c-Myc(M), N-Myc, L-Myc(L), S-Myc, and B-Myc), GLIS family genes (GLIS1 (G), GLIS 2, and GLIS 3), Klf family genes (KLF1, KLF2, KLF3, KLF4(K), KLF5, KLF6, KLF7, KLF8, KLF9, KLF10, KLF11, KLF12, KLF13, KLF14, KLF15, KLF16, and KLF17), Oct family genes, Sox family genes, and Lin-28.

Abstract: Methods are provided for extracting bone marrow cells from bone obtained from deceased donors, for preparing the bone marrow for cryopreservation and for obtaining desired cells from cryopreserved and fresh bone marrow.

Abstract: Methods are provided for extracting bone marrow cells from bone obtained from deceased donors, for preparing the bone marrow for cryopreservation and for obtaining desired cells from cryopreserved and fresh bone marrow.

Abstract: Methods are provided for extracting bone marrow cells from bone obtained from deceased donors, for preparing the bone marrow for cryopreservation and for obtaining desired cells from cryopreserved and fresh bone marrow.

Abstract: Methods are provided for extracting bone marrow cells from bone obtained from deceased donors, for preparing the bone marrow for cryopreservation and for obtaining desired cells from cryopreserved and fresh bone marrow.

Abstract: Methods are provided for extracting bone marrow cells from bone obtained from deceased donors, for preparing the bone marrow for cryopreservation and for obtaining desired cells from cryopreserved and fresh bone marrow.

Abstract: A self-replicating RNA for inducing somatic differentiation of unmodified adult stem cells is described. Methods of differentiating unmodified adult stem cells into functional beta-like cells are also described, as well as compositions, tissues and devices containing such cells. The method requires inducing sequential expression of PDX1 before NGN3, and NGN3 before MAFA in these stem cells to form reprogrammed beta-cells. Self-replicating RNAs are provided and introduced into the adult stem cells to induce the sequential expression. Methods of treating diabetes are also provided, comprising obtaining stem cells, preferably from a patient with diabetes, inducing sequential expression of PDX1>NGN3>MAFA, in said stem cells to form reprogrammed beta-cells, and introducing said reprogrammed beta-cells into a pancreas of said patient.

Abstract: Embodiments of the present disclosure relate generally to the production of therapeutic mesenchymal stem cells (MSCs). More particularly, the present disclosure relates to the use of cell culture compositions and methods for generating MSCs that secrete neurotrophic factors and synaptic organizing agents for the treatment of neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). As such, the present disclosure addresses the need for establishing a reliable source of therapeutic stem cells useful for the treatment of neurodegenerative diseases.

Abstract: Human pluripotent stem cells (hPSCs) are promising cell source to produce therapeutic endocrine cells for diabetes treatment. A gel solution made by decellularized tissue-specific extracellular matrix (dpECM) significantly promotes three-dimensional (3D) islet-like organogenesis during induced hPSC differentiation into endocrine lineages. Islet organoids are self-organized even in a two-dimensional (2D) culture mode. Cells derived from hPSCs differentiated on such ECM coated substrates exhibit similar cellular composition to native pancreatic islets. These cells express islet signature markers insulin, PDX-1, C-peptide, MafA, glucagon, somatostatin, and pancreatic polypeptide, and secrete more insulin in response to glucose level compared to a traditional matrix substrate (Matrigel). The dpECM facilitates generating more C-peptide+/glucagon? cells rather than C-peptide+/glucagon+ cells. Remarkably, dpECM also facilitated intra-organoid vascularity by generating endothelial cells and pericytes.

Abstract: Embodiments disclosed herein describe systems and methods associated with light mounting systems. Embodiments may include lighting shelves that are configured to be mounted to a fixed structure, such as to a wall or supports within a room via a cantilever design that is mounted to strut channels. The lighting shelves may be anchored at only a single end to the strut channels, and the lighting shelves may protrude away from the strut channels. The lighting shelves may have a sufficient width and length to cover an entire region of interest below the lighting shelves, which may enable to lighting shelves to uniformly distribute light to plants.

Abstract: The present invention provides a method of fusing cell masses. A method of fusing cell masses, comprising seeding cell masses on a plane capable of cell adhesion and culturing the cell masses as a culture medium is fed from both the obverse and reverse sides of the cell mass-seeded plane.

Abstract: Disclosed herein are methods for the production of mutant bacteriophages with altered host range. Additionally, disclosed herein are methods and systems for rapid detection of microorganisms such as Listeria spp. in a sample. A genetically modified bacteriophage is also disclosed which comprises an indicator gene in the late gene region. The specificity of the bacteriophage, such as Listeria-specific bacteriophage, allows detection of a specific microorganism, such as Listeria spp. and an indicator signal may be amplified to optimize assay sensitivity.

Abstract: The present invention relates to the fields of life sciences and medicine. Specifically, the invention relates to cancer therapies of humans. More specifically, the present invention relates to oncolytic adenoviral vectors alone or together with therapeutic compositions for therapeutic uses and therapeutic methods for cancer. In one aspect the present invention relates to separate administration of adoptive cell therapeutic composition and oncolytic adenoviral vectors. Furthermore, the present invention relates to a pharmaceutical kit and a pharmaceutical composition, both utilizing oncolytic adenoviral vectors.

Abstract: The present application provides engineered polypeptides having imine reductase activity, polynucleotides encoding the engineered imine reductases, host cells capable of expressing the engineered imine reductases, and methods of using these engineered polypeptides with a range of ketone and amine substrate compounds to prepare secondary and tertiary amine product compounds.

Abstract: Variant B4GALT1 genomic, mRNA, and cDNA nucleic acid molecules, and polypeptides, methods of detecting the presence of these molecules, methods of modulating endogenous B4GALT1 genomic, mRNA, and cDNA nucleic acid molecules, and polypeptides, methods of ascertaining the risk of developing cardiovascular conditions by detecting the presence or absence of the variant B4GALT1 genomic, mRNA, and cDNA nucleic acid molecules, and polypeptides, and methods of treating cardiovascular conditions are provided herein.

Abstract: Compositions and methods related to anucelate cells (e.g., bacterial minicells) for pesticide degradation applications including related cells, polypeptides, and vectors.

Abstract: Provided herein are systems, compositions, and methods of introducing protective and/or loss-of-function variants of CCR5 and CCR2. Variants may be introduced using a CRISPR/Cas9-based nucleobase editor or other guide nucleotide sequence-programmable DNA binding protein domain-based fusion protein described herein. Further provided herein are compositions and methods of preventing and treating conditions related to HIV infection and progression as well as to AIDS.

Abstract: Engineered CRISPR-Cas9 nucleases with altered and improved PAM specificities and their use in genomic engineering, epigenomic engineering, and genome targeting.

Abstract: Engineered CRISPR-Cas9 nucleases with altered and improved PAM specificities and their use in genomic engineering, epigenomic engineering, and genome targeting.

Abstract: The present invention provides engineered DNase proteins (including DNase1-like 3 and DNase1) that are useful for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In some aspects, the invention provides compositions and methods for preventing or treating vascular occlusion involving NETs. As demonstrated herein, NETs participate in a non-canonical mechanism for vascular occlusion, which is not dependent on fibrin or platelets.

Abstract: Compositions and methods for delivering a therapeutic protein to the central nervous system (CNS), in order to treat diseases and disorders that impair the CNS, such as treating lysosomal storage diseases are disclosed. Therapeutic proteins delivered via a therapeutically effective amount of a nucleotide composition encoding the therapeutic protein conjugated to a cell surface receptor-binding protein that crosses the blood brain barrier (BBB) are provided.

Abstract: The present invention relates to oxidation stable alpha-amylase variants. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

Abstract: The present invention relates to isolated polypeptides having lysozyme 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: The disclosure provides methods and compositions for treating blood diseases/disorders, such as sickle cell disease, hemochromatosis, hemophilia, and beta-thalassemia. For example the disclosure provides therapeutic guide RNAs that target the promotor of HBG1/2 to generate point mutations that increase expression of fetal hemoglobin. As another example, the disclosure provides therapeutic guide RNAs that target mutations in HBB, Factor VIII, and HFE to treat sickle cell disease, beta-thalassemia, hemophilia and hemochromatosis. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins are in complex with nucleic acids, such as guide RNAs (gRNAs), which target the fusion proteins to a DNA sequence (e.g., an HBG1 or HBG2 protmoter sequence, or an HFE, GBB, or F8 gene sequence).

Abstract: The present invention provides engineered phenylalanine ammonia-lyase (PAL) polypeptides and compositions thereof, as well as polynucleotides encoding the engineered phenylalanine ammonia-lyase (PAL) polypeptides.

Abstract: Provided herein are methods and compositions and kits related to identification and/or treatment of subjects, including subjects with hyperuricemia, gout or a condition associated with gout, and for preventing gout flare.

Abstract: The present invention relates to RNA therapy and, in particular, decreasing immunogenicity of RNA. Specifically, the present invention provides methods for decreasing immunogenicity of RNA, said methods comprising modifying the nucleotide sequence of the RNA by reducing the uridine (U) content, wherein said reduction of the U content comprises an elimination of U nucleosides from the nucleotide sequence of the RNA and/or a substitution of U nucleosides by nucleosides other than U in the nucleotide sequence of the RNA. Using RNA having decreased immunogenicity allows administration of RNA as a drug to a subject, e.g. in order to obtain expression of a pharmaceutically active peptide or protein, without eliciting an immune response which would interfere with therapeutic effectiveness of the RNA or induce adverse effects in the subject.

Abstract: The invention relates to novel libraries of linear and cyclic peptides, and methods of generating and screening such libraries for biological, pharmaceutical and other uses.

Abstract: The present disclosure relates to methods and systems for sample processing and analyzing when the total quantity of input sample is low or when a target of interest is present as a relatively minor or rare population within the overall sample. The disclosure particularly relates to analyzing nucleic acid samples, including samples where a target nucleic acid of interest is present as a relatively low proportion of the overall nucleic acids.

Abstract: The present technology relates to methods and compositions that provide for improved detection of target molecules in, for example, bioengineering.

Abstract: The present disclosure describes oligonucleotide-tethered nucleotides, methods of making them, and methods of using them. The oligonucleotide-tethered nucleotides comprise, in some embodiments, a nucleotide linked to an oligonucleotide of from about 3 to about 100 nucleotides in length. These oligonucleotide-tethered nucleotides can be used to label a plurality of different types of nucleic acids in a plurality of different situations with a known oligonucleotide, which can serve as a barcode in some embodiments. The resulting oligonucleotide-labeled nucleic acids oligonucleotides can be used in a variety of nucleic acid sequencing methods.

Abstract: The present invention provides nucleic acid templates (e.g., including orthogonal codon sets (e.g., codons from orthogonal codon sets depicted in Tables 5 or 7)) for DNA-templated methods of synthesizing, selecting, and amplifying compounds (e.g., polymers and/or small molecules) described herein. Also provided are novel macrocyclic compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, libraries, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing a disease (e.g., a disease associated with aberrant enzyme activity (e.g., aberrant protease and/or kinase activity (e.g., aberrant IDE activity)), impaired insulin signaling, or insulin resistance in a subject (e.g., a subject having diabetes).

Abstract: The invention provides barcode libraries and methods of making and using them including obtaining a plurality of nucleic acid constructs in which each construct comprises a unique N-mer and a functional N-mer and segregating the constructs into a fluid compartments such that each compartment contains one or more copies of a unique construct. The invention further provides methods for digital PCR and for use of barcode libraries in digital PCR.