Abstract: Compositions and methods for treating lysosomal storage diseases are disclosed. Biotherapeutic complexes containing an internalization effector binding domain and a lysosomal replacement enzyme activity are disclosed. The biotherapeutic complexes are capable of entering cells, segregating to the lysosome, and delivering the replacement enzyme activity to the lysosome.

Abstract: Provided are a hexuronate C4-epimerase variant with improved activity in converting D-fructose by D-tagatose of hexuronate C4-epimerase and a method for production of D-tagatose using them.

Abstract: A group of arabinose isomerases are disclosed that provide effective amounts of activity for use of arabinose in production of ethanol, when expressed in yeast cells expressing the other enzymes of an arabinose utilization pathway. The group of arabinose isomerases represents a clade of a phylogenetic tree, having a distinguishing conserved amino acid sequence motif. Other useful arabinose isomerases are also disclosed.

Abstract: Enzyme-immobilizing MOFs and methods for their use in enzymatically catalyzed reactions are provided. The MOFs are channel-type MOFs that present a hierarchical pore structure comprising a first set of large channels sized for enzyme immobilization and a second set of smaller channels running alongside of the large channels that remain enzyme-free and allow for reactant delivery to the enzymes and product expulsion from the larger channels.

Abstract: This invention relates to a single cell assay for determining the effect of chromosomal contact on the transcriptional activity of genes of interest in a cell and to methods of silencing gene expression in a cell by way of perturbing gene regulatory elements which are engaged in chromosomal contact.

Abstract: Disclosed is a method for the selection of aptamers that does not require immobilization of the target or the oligonucleotide library. The method includes: (i) combining a selection library of oligonucleotides that contain a random region flanked by primer recognition sites with blocker oligonucleotides that anneal to the primer recognition sites; (ii) exposing the blocked selection library to an immobilization field including random oligonucleotides and removing unbound selection library oligonucleotides; (iii) recovering the selection library oligonucleotides that bound to the immobilization field and combining with a target analyte of interest; (iv) exposing the selection library oligonucleotides-target analyte mixture to an immobilization field; and (v) recovering those selection library oligonucleotides that did not bind to the immobilization field.

Abstract: The invention features compositions and methods that are useful for identifying allele variants that modulate gene expression. Compositions and articles defined by the invention were isolated or otherwise manufactured.

Abstract: The disclosed embodiments relate to method, apparatus and system for high throughput single-cell DNA sequencing with droplet microfluidic. In an exemplary embodiment, a method for analyzing nucleic acids within a cell includes the steps of: (a) flowing individual cells together with a material capable of forming a polymer or microsphere that retains nucleic acids into a carrier fluid such that droplets are formed; (b) breaking the emulsion and collecting the microsphere hydrogels in an aqueous fluid; and (c) performing combinatorial labeling on the nucleic acids contained within the microspheres/hydrogels.

Abstract: The invention generally relates to compositions and methods for designing and producing functional DNA binding effector molecules and associated customized services, tool kits and functional assays. In some aspects, the invention provides methods and tools for efficient assembly of customized TAL effector molecules. Furthermore, the invention relates to uses of TAL effector molecules and functional evaluation of such TAL by, for example, customized assays.

Abstract: This invention provides biosensors, cell models, and methods of their use for monitoring chloride ion, where the biosensors can include targeting domains, sensing domains and reporting domains. Biosensors can be introduced into cells reprogrammed to represent experimental or pathologic cells of interest, including as detectors of chloride ions, as TempoChloro™ accomplishes.

Abstract: Methods and systems of cell-fee enzyme discovery and optimization are provided.

Abstract: Methods and compositions of single tube preparation of sequencing libraries from a target DNA are provided. The methods include contacting the DNA with a composition comprising Cas9 endonuclease, a first and a second guide RNAs, a ligase, and sequencing adapters, subjecting the composition to thermal cycling to cleave the DNA at the sites flanking the regions of interest by the RNA guided endonuclease, and subjecting the composition to a temperature to allow ligation of the cleaved DNA fragments including the regions of interest with the sequencing adapters to generate the sequencing libraries.

Abstract: Disclosed herein are protein translation switches and conditional gene expression systems that are compatible with retroviral and lentiviral gene delivery. The linking of a protein translation switch to a 3? gene of interest suppresses translation of the gene of interest, and the alteration of the protein translation switch by DNA recombinase-mediated DNA recombination relieves the suppressed translation of the 3? gene of interest. Also disclosed herein are methods of mimicking clinical pharmacology in a pre-clinical setting.

Abstract: Molecules are provided for inducing or facilitating exon skipping in forming spliced mRNA products from pre-mRNA molecules in cells. The molecules may be provided directly as oligonucleotides or expression products of vectors that are administered to a subject. High rates of skipping can be achieved. High rates of skipping reduce the severity of a disease like Duchene Muscular Dystrophy so that the disease is more like Becker Muscular Dystrophy. This is a severe reduction in symptom severity and mortality.

Abstract: The invention provides a method for generating an oligonucleotide with which an exon may be skipped in a pre-mRNA and thus excluded from a produced mRNA thereof. Further provided are methods for altering the secondary structure of an mRNA to interfere with splicing processes and uses of the oligonucleotides and methods in the treatment of disease. Further provided are pharmaceutical compositions and methods and means for inducing skipping of several exons in a pre-mRNA.

Abstract: This disclosure relates to the use of miRNA-483 and its target genes, UBE2C, pVHL and HIF1alpha, in managing the treatment of cardiovascular and inflammatory diseases. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a miR-483 mimic and/or an HIF inhibitor and a pharmaceutically acceptable excipient for use in treating or preventing a vascular disease or condition. In certain embodiments, the miR-483 mimic is a double stranded nucleobase polymer or an expression vector that expresses mature human miR-483-5p and miR-483-3p sequences or operable fragments and variants.

Abstract: The. invention relates to a method for inducing or promoting skipping of exon 45 of DMD pre-mRNA in a Duchenne Muscular Dystrophy patient, preferably in an isolated (muscle) cell, the method comprising providing said cell with an antisense molecule that binds to a continuous stretch of at least 21 nucleotides within said exon. The invention further relates to such antisense molecule used in said method.

Abstract: The present invention relates functional ligands to target molecules, particularly to functional nucleic acids and modifications thereof, and to methods for simultaneously generating, for example, numerous different functional biomolecules, particularly to methods for generating numerous different functional nucleic acids against multiple target molecules simultaneously. The present invention further relates to functional ligands which bind with affinity to target molecules such as immunoglobulins, such as IgG.

Abstract: The present invention provides an oligodeoxynucleotide containing humanized K type CpG oligodeoxynucleotide and poly deoxyadenylate, wherein the poly deoxyadenylate is placed on the 3?-side of the humanized K type CpG oligodeoxynucleotide. In addition, the present invention provides a complex containing the aforementioned oligodeoxynucleotide and ?-1,3-glucan.

Abstract: The invention relates to a genetically transformed or transfected bacterial cell chromosome wherein said cell is made to express interfering RNA (siRNA) active against at least one gene encoding a cancer promoting or sustaining protein such as an oncogene, a chemo-resistant gene or a metabolic gene; siRNA cassette encoding at least one siRNA active against said gene; a bacterial cell with said siRNA cassette integrated within the bacterial chromosome; a method of treating cancer, particularly but not exclusively prostate, breast or colorectal cancer, employing the use of said bacterial cell with a chromosomally integrated siRNA cassette; and use of said bacterial cell with a chromosomally integrated siRNA cassette to treat said cancer.

Abstract: Described herein are methods of treating inflammatory bowel disease (IBD) in a patient having IBD using SMAD7 antisense oligonucleotides.

Abstract: MicroRNA-30 is identified as being dysregulated in adipose tissue macrophages during obesity and can be used in treatment of disease in which adipose tissue macrophage polarization dysregulation plays a part. Increased concentration of microRNA-30, e.g., via pharmaceutical delivery, can decrease the polarization of macrophages, and in particular adipose tissue macrophages, to inflammatory M1 phenotype and can decrease expression of pro-inflammatory cytokines. One or more members of the miR-30 family can be utilized in the methods. Methods can be beneficial in treatment of a large number of inflammatory diseases including obesity, diabetes, cancer, autoimmune, etc.

Abstract: A method for reducing neovascularization in an ocular tissue is carried out by contacting the tissue with an inhibitor of endomucin expression or activity.

Abstract: Fungi that are genetically inactivated for the mstC gene (or a homolog thereof) are provided, which can also be genetically modified to increase production of heterologous proteins from a glucoamylase promoter. Methods of using these fungi, for example to degrade a biomass, are also provided.

Abstract: The present invention generally relates to the field of fermentation technology and microorganisms useful for such fermentations. The invention also relates to materials including nucleic acids and proteins useful for altering fermentation characteristics of microorganisms, and to microorganisms comprising such nucleic acids and/or proteins.

Abstract: The present invention aims to provide a promoter showing high expression activity in microorganisms belonging to the genus Mortierella. The present invention provides a polynucleotide which contains any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 28, or a variant thereof.

Abstract: A method for deleting a region of DNA in a plant. In some embodiments, the method comprises transforming a plant with a nucleic acid molecule, wherein the nucleic acid molecule encodes one or more zinc finger nuclease(s) (ZFNs) operably linked to one or more tissue-specific promoter(s), e.g., a pollen-specific promoter. Methods include excising native genes in a plant. Accordingly, in some embodiments, ZFNs are engineered that recognize sequences that flank native plant genes. In further embodiments, ZFNs are expressed under the control of developmental stage-specific promoters, such that, for example, nucleic acid sequences are specifically excised in plants during relatively late stages of development. Nucleic acid molecules useful for carrying out disclosed methods and plants produced by the methods are included.

Abstract: We identified 17 transcription factor genes that regulate lipid production and activity in an organism. We subsequently detailed characterization of one of them (psr1). Constructs, methods and systems for enhancing or increasing lipid production in an organism are described.

Abstract: Disclosed herein are polynucleotides and the polypeptides encoded thereby and their use to increase biomass production by photosynthetic organisms. Also provided are photosynthetic organisms transformed by such polynucleotides and expressing such polypeptides.

Abstract: Provided herein are modified Rubisco large subunit proteins and nucleid acids encoding such proteins, as well as photosynthetic organism transformed with said nucleic acids and expressing said proteins. In certain embodiments, photosynthetic organisms containing said modified Rubisco large subunit proteins exhibit increased biomass production.

Abstract: Disclosed herein are compositions and methods for creating sterile plants by genetically ablating microspore and megaspore mother cells. Also disclosed herein are methods of restoring fertility of sterile male and female plants.

Abstract: Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR/Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.

Abstract: Described is a method for the production of isobutene from 3-methylcrotonyl-CoA comprising the steps of: (a) enzymatically converting 3-methylcrotonyl-CoA into 3-methylbutyric acid; and (b) further enzymatically converting the thus produced 3-methylbutyric acid into isobutene. The conversion of 3-methylcrotonyl-CoA into 3-methylbutyric acid can be achieved by first enzymatically converting 3-methylcrotonyl-CoA into 3-methyl butyryl-CoA and further enzymatically converting the thus produced 3-methylbutyryl-CoA into 3-methylbutyric acid. Alternatively, the conversion of 3-methylcrotonyl-CoA into 3-methylbutyric acid can be achieved by first enzymatically converting 3-methylcrotonyl-CoA into 3-methylcrotonic acid and then further enzymatically converting the thus produced 3-methylcrotonic acid into 3-methylbutyric acid.

Abstract: The present invention provides a Clostridium species comprising a non-native gene capable of expressing (R)-3-hydroxybutyryl-Co A dehydrogenase. Also provided is a method of producing (R)-3-hydroxybutyric acid, or a salt thereof, and/or (R) 1,3-butanediol using such Clostridium.

Abstract: Provided herein is a recombinant nucleic acid molecule, a recombinant microorganism, and a method for fermentative production of n-butylacrylate and other esters from alcohols and acyl-CoA units using alcohol acyl transferase enzymes.

Abstract: The invention relates to a method and an apparatus for an enzymatic hydrolysis in which plant based raw material is hydrolysed by means of enzymes. The plant based raw material (1) is fed to the first enzymatic hydrolysis stage (2), the plant based raw material (1) is hydrolysed in at least two enzymatic hydrolysis stages (2,4), a liquid fraction (5a,5b) comprising carbohydrates is separated from a solid fraction (6a,6b) in a solid-liquid separation stage (7a,7b) after each enzymatic hydrolysis stage (2,4), and the solid fraction (6a) is supplied to the next enzymatic hydrolysis stage (4) in which the solid fraction is treated, and the solid fraction (6b) is recovered after the last solid-liquid separation stage (7b). Further, the invention relates to the liquid fraction and the solid fraction and their use.

Abstract: A method efficiently produces a sugar liquid having a high quality from a cellulose-containing biomass. More specifically, the method includes: the step of obtaining an alkaline filtrate by allowing an alkaline aqueous medium to pass through a cellulose-containing biomass; the recirculation filtration step of allowing the alkaline filtrate to repeatedly pass through the cellulose-containing biomass to produce a cellulose-containing solid component; and the step of hydrolyzing the cellulose-containing solid component to obtain the sugar liquid.

Abstract: The present invention provides methods of amplifying a target nucleic acid utilizing a circularized template. Circularization may be achieved utilizing a bridging oligonucleotide or an inverter primer. The bridging oligonucleotide or inverted primer is extended forming a concatemeric amplicon that can then be used as a template to provide exponential amplification of the target nucleic acid.

Abstract: The disclosure provides methods for making a polynucleotide wherein the addition of nucleotides can be physically, chemically and/or enzymatically controlled. The methods include combining a selected nucleotide, cations, an error prone or template independent DNA polymerase at a reaction site including an initiator sequence attached thereto and having a 3? terminal nucleotide, wherein the reaction reagents can be modulated and under conditions that allow covalent addition of one or more of a selected nucleotide to the 3? terminal nucleotide such that the selected nucleotide becomes a 3? terminal nucleotide, and repeating the addition step until the polynucleotide is formed.

Abstract: Provided herein, among other things, is a conjugate comprising a polymerase and a nucleoside triphosphate, where the polymerase and the nucleoside triphosphate are covalently linked via a linker that comprises a cleavable linkage. A set of such conjugates, where the conjugates correspond to G, A, T (or U) and C is also provided. Methods for synthesizing a nucleic acid of a defined sequence are also provided. The conjugates can also be used for sequencing applications.

Abstract: The present invention provides a method for high yield and stable production of carotenoids through microbial culture. The present invention provides a method for culture of carotenoid-producing bacteria, which comprises culturing carotenoid-producing bacteria in a medium containing cobalt or a cobalt salt at a concentration of 0.005 ?mol/L to 20 ?mol/L.

Abstract: The present invention relates to a method for mass production of ginsenoside Rh2-Mix. The present invention includes treating PPD-Mix with an organic acid and heat to obtain Rg3-Mix and treating the obtained Rg3-Mix using a recombinant GRAS strain in the Rg3-Mix to produce Rh2-Mix, and thereby facilitates the mass production of ginsenoside Rh2-Mix using ?-glucosidase, which has been known to be difficult. Further, the present invention is advantageous in that the Rh2-Mix can be produced in high yield even at high temperatures, and mass production thereof for industrial purposes is practical as the production process is simple and more economical than direct use of an enzyme.

Abstract: The present disclosure relates to the use of an amino acid dehydrogenase in combination with a cofactor regenerating system comprising a ketoreductase. In particular embodiments, the process can be used to prepare L-tert-leucine using a leucine dehydrogenase.

Abstract: The present invention provides a method for determining whether or not all of pythiums contained in a test sample are non-phytopathogenic. The method comprises: (a) putting the test sample on a front surface of a film comprising a through-hole having a cross-sectional area of not less than 0.785 square micrometers and not more than 7.065 square micrometers; (b) leaving the test sample at rest after the step (a); (c) observing a back surface of the film after the step (b); and (d) determining that all of the pythiums contained in the test sample are non-phytopathogenic, if pseudohyphae are not found on the back surface of the film in the step (c).

Abstract: The present invention relates to a method of obtaining peptides from procaryotic and/or eucaryotic cells.

Abstract: The present invention relates to a method for determining or predicting the response of a patient diagnosed with melanoma to targeted pharmacotherapy. The present invention also aims to provide methods and devices for predicting the response of patients diagnosed with melanoma to specific medicaments. More specifically, the present invention provides methods which measure kinase and/or phosphatase activity by studying phosphorylation levels and profiles and inhibitions thereof by drugs in samples, preferably blood samples, of said patients.

Abstract: This invention relates to methods of preparing nucleic acid aptamers having selectivity for target substrates. In particular the present invention provides for a method of identifying a ligand binding domain (LBD) in an aptamer by providing a first incubation solution by incubating an aptamer with a target substrate in a first appropriate solvent; and adding an exonuclease enzyme to the first incubation solution to form a second incubation solution in a second appropriate solvent and incubating the second incubation solution, wherein the exonuclease enzyme digests aptamer and provides an aptamer comprising the ligand binding domain.

Abstract: LIFE-ChIP-seq (Low-Input Fluidized-bed Enabled Chromatin Immunoprecipitation followed by sequencing), an automated and high-throughput microfluidic platform capable of running multiple sets of ChIP assays in as little as 1 hour with as few as 50 cells per assay. This technology enables testing of a large number of samples and replicates with low-abundance primary samples in the context of precision medicine.

Abstract: The present disclosure provides methods and compositions for nucleic acid detection. Nucleic acids may be derived from any source including, for example, viruses, bacterial cells, and eukaryotic cells. The methods of the present disclosure may be used to detect the presence of at least one member of a plurality of nucleic acids in a sample. The methods of the present disclosure may be used to detect the presence of both a first and second member of a plurality of nucleic acids in a sample. Nucleic acids may be detected by the generation of one or more signals.

Abstract: The present disclosure provides a nucleic acid amplification method. The method comprises forming an enrichment culture by contacting a sample with a nutrient medium having a formulation that does not include a phosphate buffer component; holding the enrichment culture for a period of time at a temperature that facilitates growth of a target microorganism; after holding the enrichment culture, forming an aqueous composition by mixing a first volume of the enrichment culture with a second volume of a lysis buffer; contacting the aqueous composition with an effective amount of a water-insoluble material that sequesters a substance that interferes with a polymerase-mediated nucleic acid amplification reaction; subjecting the aqueous composition to a thermal lysis process; and, after subjecting the aqueous composition to the thermal lysis process, subjecting a portion of the aqueous composition to a nucleic acid amplification process. A composition for a lysis buffer is also disclosed.