Abstract: Transgenic host cells, vectors useful for making transgenic host cells, and kits useful for making transgenic host cells are described. Also described are transgenic plants. In some embodiments, transgenic host cells express a 4-hydroxyphenylacetaldehyde synthase (4HPAAS). In some embodiments, transgenic host cells express a tyrosol:UDP-glucose 8-O-glucosyltransferase (T8GT). The transgenic host cells are useful for biosynthesis of one or more of salidroside, icariside D2, tyrosol, and 4-hydroxypenylacetaldehyde.

Abstract: The present disclosure provides methods and compositions related to the combination therapy of a macrophage-directed immunotherapy and a targeted agent. The combination of the macrophage-directed immunotherapy and a targeted agent is useful in treating and/or preventing cancer (e.g., lung cancer) in a subject.

Abstract: Non-genetically engineered mammalian cells modified by sortase-mediated conjugation of an agent thereto are provided. Methods of conjugating agents to non-genetically engineered mammalian cells using sortase are provided. Methods of using the cells, e.g., for diagnostic and/or therapeutic purposes, are provided.

Abstract: The present disclosure provides methods and compositions related to identifying agents that modulate macrophage function. The agents identified may be useful alone or in combination for treating and/or preventing diseases related to macrophage function (e.g., cancer) in a subject.

Abstract: The present disclosure, at least in part, relates to compositions (e.g., engineered nucleic acids and engineered proteins) and methods for increasing gene expression. The engineered proteins include RNA-binding proteins (e.g., RNA-binding proteins that comprise a Interleukin Enhancer Binding Factor 3 (ILF3) sequence, a Cas sequence, or a combination thereof). In some aspects, the disclosure provides methods of identifying engineered nucleic acids that are shorter in length than a gene of interest to induce expression of the gene of interest and also provides RNA-binding proteins for inducing gene expression.

Abstract: Lyciumin cyclic peptides and methods of producing lyciumin cyclic peptides are described. A host cell can include a transgene encoding a lyciumin precursor peptide, or a biologically-active fragment thereof. The lyciumin precursor peptide, or biologically-active fragment thereof, can include one or more core lyciumin peptide domains. The transgene can be expressed in the host cell to thereby produce a lyciumin precursor peptide, or biologically-active fragment thereof. The lyciumin precursor peptide, or biologically-active fragment thereof, can be converted to one or more lyciumin cyclic peptides in the host cell. A library of nucleic acids encoding lyciumin precursor peptides, or biologically-active fragments thereof, can be generated.

Abstract: Disclosed are methods of altering expression of a gene with a promoter region CTCF binding site. Also disclosed are compositions and methods useful for treating a disease or condition involving over-expression or under-expression of a gene with a promoter region CTCF binding site. Further disclosed are cells and non-human animals with modified a promoter region CTCF binding site, as well as methods for screening for compounds that can modify the expression of a gene with a promoter region CTCF binding site.

Abstract: Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are methods, uses, and kits involving the disclosed compounds and pharmaceutical compositions thereof for treating and/or preventing a disease (e.g., a metabolic disorder (e.g., obesity, diabetes), a hypoxia related disease (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, neurodegenerative disorder, hypoxia, ischemia, oxidative stress, or a mitochondrial DNA related disorder), or a disease resulting from rhodoquinone depletion (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, metabolic disorder, or neurodegenerative disorder)) in a subject.

Abstract: The disclosed Hi-C protocol can identify genomic loci that are spatially co-located in vivo. These spatial co-locations may include, but are not limited to, intrachromosomal interactions and/or interchromosomal interactions. Hi-C techniques may be applied to many different scales of interest. For example, on a large scale, Hi-C techniques can be used to identify long-range interactions between distant genomic loci.

Abstract: The present disclosure provides compounds of any one of Formulae (A) to (L). The present disclosure also provides compositions, uses, and methods that include or involve a compound described herein, a serine/threonine-protein kinase B-Raf (BRAF) inhibitor, an epidermal growth factor receptor (EGFR) inhibitor, a vascular endothelial growth factor 1 (VEGFR1) inhibitor, a fibroblast growth factor receptor 1 (FGFR1) inhibitor, or a combination thereof. The compounds, compositions, uses, and methods are useful in changing the pluripotency state of a vertebrate cell to a more naïve state.

Abstract: Provided herein are methods for producing site specific PEG modifications to single domain antibodies (e.g., VHHs). Methods for producing site-specifically conjugated bivalent single domain antibodies (e.g., VHHs) are also provided. Methods for labeling (e.g., with a fluorophore or radionuclide) site-specifically PEGylated single domain antibodies and site-specifically conjugated bivalent single domain antibodies are also provided.

Abstract: Disclosed are methods, compositions, proteins, nucleic acids, cells, vectors, compounds, reagents, and systems for the preparation of kavalactones, flavokavains, and kavalactone and flavokavain biosynthetic intermediates using enzymes expressed in heterologous host cells, such as microorganisms or plants, or using in vitro enzymatic reactions. This invention also provides for the expression of the enzymes by recombinant cell lines and vectors. Furthermore, the enzymes can be components of constructs such as fusion proteins. The kavalactones produced can be utilized to treat anxiety disorder, insomnia, and other psychological and neurological disorders. The flavokavains produced can be utilized to treat various cancers including colon, bladder, and breast cancers.

Abstract: The present disclosure provides, in various aspects, engineered alcohol tolerant yeast and methods of producing high concentrations of biofuels and bioplastics from toxic feedstocks.

Abstract: Disclosed are methods, systems, cells and compositions directed to modeling a physiologic or pathologic process in an animal using a set of yeast genes analogous to a set of animal genes and augmenting the physiologic or pathologic process in the animal with predicted gene interactions based on the interactions between the set of yeast genes. Also disclosed are methods of screening for and using therapeutics for neurodegenerative proteinopathies.

Abstract: The invention relates to methods of modifying DNA methylation by contacting a cell with a catalytically inactive site specific nuclease fused to an effector domain having methylation or demethylation activity and one or more guide sequences.

Abstract: Potassium chloride cotransporter-2 (KCC2) plays a critical role in brain function, and deficiency in KCC2 has been linked to neurological diseases, psychiatric disorders, and central nervous system injuries. In particular, Rett syndrome (RTT), a severe neurodevelopmental disorder caused by mutations in the X-linked gene Methyl CpG binding Protein 2 (MECP2), has been linked to deficits in KCC2. The disclosure reports the use of CRISPR/Cas9 genome-editing technology to generate stem cell-derived, genetically defined KCC2 reporter human neurons for large-scale compound screening. This screening platform has been utilized to identify a number of small molecule compounds that are capable of enhancing KCC2 expression in both wild-type and RTT neurons, as well as organotypical brain slices cultured from wild-type mice.

Abstract: Provided herein are methods for producing site specific PEG modifications to single domain antibodies (e.g., VHHs). Methods for producing site-specifically conjugated bivalent single domain antibodies (e.g., VHHs) are also provided. Methods for labeling (e.g., with a fluorophore or radionuclide) site-specifically PEGylated single domain antibodies and site-specifically conjugated bivalent single domain antibodies are also provided.

Abstract: Work described herein reveals 3D regulatory landscapes of hESCs representative of early human development. This work also demonstrates that cohesin-associated CTCF loops, and the cohesin-associate enhancer-promoter loops within them, dominate the organization of TADs. The CTCF-CTCF loops form a chromosomal scaffold of insulated neighborhoods that are largely preserved in vertebrates, and enhancer-promoter interactions occur within these neighborhoods. Genes are regulated in the context of conserved insulated neighborhood structures. Loss of neighborhood structures occurs frequently in cancer cells, and proto-oncogenes can be activated by genetic alterations that disrupt specific 3D chromosome structures.

Abstract: Methods for the in vitro production of enucleated red blood cells and the enucleated red blood cells thus prepared are provided. Such enucleated red blood cells may express a sortaggable surface protein, which allows for surface modification in the presence of a sortase. Also described herein are surface modified enucleated red blood cells, e.g., conjugated with an agent of interest such as a peptide, a detectable label, or a chemotherapeutic agent, and uses thereof in delivering the agent to a subject.

Abstract: The invention provides methods for reprogramming somatic cells to generate multipotent or pluripotent cells. Such methods are useful for a variety of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a less differentiated state.