Abstract: The pharmaceutical use of lipases related to the Thermomyces lanuginosus (Humicola lanuginosa) lipase comprising amino acids 1-269 of SEQ ID NO: 2, optionally in combination with a protease and/or an amylase. Examples of medical indications are: Treatment of digestive disorders, pancreatic exocrine insufficiency (PEI), pancreatitis, cystic fibrosis, diabetes type I, and/or diabetes type II. The lipases of the invention have, e.g., an improved digestion performance in vitro, an improved activity at a pH in the neutral range, an improved stability at low pH, an are stable against protease-degradation, and/or are stable in the presence of pepsin and bile salts. The invention also relates to methods of determining digestion performance in vitro of lipases, as well as to certain novel variants of the lipase of T. lanuginosus.

Abstract: The present invention concerns methods and compositions related to type 3 phosphodiesterases (PDE3). Certain embodiments concern isolated peptides corresponding to various PDE3A isoforms and/or site-specific mutants of PDE3A isoforms, along with expression vectors encoding such isoforms or mutants. In specific embodiments, methods for identifying isoform-selective inhibitors or activators of PDE3 are provided, along with methods of use of such inhibitors or activators in the treatment of dilated cardiomyopathy, pulmonary hypertension and/or other medical conditions related to PDE3 effects on cAMP levels in different intracellular compartments.

Abstract: The present invention relates to isolated polypeptides having organophosphorous hydrolase activity and isolated 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: Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (?)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (?)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

Abstract: A molecular probe for use in detecting, monitoring, and/or imaging cancer cells and/or cancer cell metastasis, migration, dispersal, and/or invasion includes a targeting agent and a detectable moiety. The targeting agent specifically binds to and/or complexes with a proteolytically cleaved extracellular fragment of an immunoglobulin (Ig) superfamily cell adhesion molecule that is expressed by a cancer cell or another cell in the cancer cell microenvironment.

Abstract: A method of characterizing a person's skin imperfections uses a digital color image-taking device to take at least one digital image of an area of skin including at least one imperfection to be characterized. An apparatus for characterizing the imperfections of the skin and a method for measuring the effectiveness of a treatment for skin imperfections use an active cosmetic, dermatological or pharmaceutical agent and further measure the effectiveness of a staining method aiming to attenuate or mask skin imperfections.

Abstract: The present invention relates to polypeptides having phytase activity. These polypeptides have an amino acid sequence which has at least 70% identity to either of three phytases derived from the bacterium Buttiauxella, and which comprises at least one of the following amino acids at the position indicated: 119N, 120L, and/or 121E. These phytases have an improved specific activity. Additional specific amino acid substitutions are also disclosed which characterize and distinguish additional phytases of the invention having improved properties such as temperature and/or pH stability, pH activity profile, temperature activity profile, substrate profile, improved performance in animal feed in vitro or in vivo. The invention also relates to isolated polynucleotides encoding the polypeptides, nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

Abstract: In some embodiments, methods for ligating nucleic acid ends comprise: conducting a nucleic acid ligation reaction in the presence of at least one agent that generates a ligatable terminal 5? phosphate group by removing an adenylate group from a terminal 5? phosphate of a nucleic acid. In some embodiments, an aprataxin enzyme can catalyze removal of an adenylate group from a terminal 5? phosphate of a nucleic acid. In some embodiments, methods for ligating nucleic acid ends comprise: conducting a nucleic acid ligation reaction in the presence of an aprataxin enzyme under conditions suitable for ligating nucleic acid ends.

Abstract: The present invention relates to a recombinant E. coli strain characterized in that the organisms contains a gene coding for a protein having esterase activity. Such E. coli is suitable for the preparation of a protein with esterase activity, whereby the expression takes place without coexpression of GroEL and/or GroES from a plasmid. The expression of glutathione reductase and/or thioredoxin reductase may be abolished by mutation. Furthermore, the ability of the organism to grow under oxygen-rich conditions has been restored by mutation. The expression of the gene of the protein with esterase activity is unaccompanied by the expression of an additional gene encoding a heat shock chaperone protein.

Abstract: Disclosed is a composition comprising recombinant iduronate-2-sulfatase (IDS). The glycosylation pattern and formylglycine content of the IDS composition are different from those of Elaprase and have superior pharmaceutical efficacy and are safer than the conventional agent and thus can be effectively used for the therapy of Hunter syndrome.

Abstract: A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, A199S/F227A/S287G/A328W/Y332G, and A199S/F227A/S287G/A328W/E441D all have enhanced catalytic efficiency for (?)-cocaine compared with wild-type BChE.

Abstract: The invention provides for a method of producing an isoprenyl alkanoate in a genetically modified host cell. In one embodiment, the method comprises culturing a genetically modified host cell which expresses an enzyme capable of catalyzing the esterification of an isoprenol and a straight-chain fatty acid, such as an alcohol acetyltransferase (AAT), wax ester synthase/diacylglycerol acyltransferase (WS/DGAT) or lipase, under a suitable condition so that the isoprenyl alkanoate is produced.

Abstract: The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 82% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 82% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Abstract: Disclosed is a polymer conjugate of folic acid or a folic acid derivative, wherein an amide bond is not used. The compound has chemical stability and adequate drug release rate in the living organism. Specifically disclosed is a polymer conjugate of folic acid or a folic acid derivative, wherein a substituent represented by formula (I) is bonded to a carboxy group of a block copolymer which is composed of a polyethylene glycol and a polymer having a carboxy group in a side chain, or a pharmacologically acceptable salt thereof. [In the formula, A represents a monocyclic or fused aromatic group; G represents an optionally substituted (C1-C6) alkylene group; Y represents a hydrogen atom or a substituent; and E represents a residue of folic acid or a folic acid derivative.

Abstract: The invention relates to a synthetic phytase with elevated thermostability, elevated stability to acids at p H 2, elevated stability to pepsin and with a broadened active p H range, and to an isolated nucleic acid sequence coding for a synthetic phytase and to the use of the phytase in an animal feed for reducing the phosphate content in the slurry and to animal feed additives and animal feeds comprising the synthetic phytase.

Abstract: The present invention relates to polypeptides having phytase activity. These polypeptides have an amino acid sequence which has at least 70% identity to either of three phytases derived from the bacterium Buttiauxella, and which comprises at least one of the following amino acids at the position indicated: 119N, 120L, and/or 121E. These phytases have an improved specific activity. Additional specific amino acid substitutions are also disclosed which characterize and distinguish additional phytases of the invention having improved properties such as temperature and/or pH stability, pH activity profile, temperature activity profile, substrate profile, improved performance in animal feed in vitro or in vivo. The invention also relates to isolated polynucleotides encoding the polypeptides, nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

Abstract: The invention is directed to a treatment of systemic bacterial, fungal and protozoan infections. The inventive method comprises introducing a DNase enzyme into a circulating blood system of a patient diagnosed with systemic infection caused by bacteria, fungi or protozoa, wherein said DNase enzyme destroys extracellular DNA in said blood of said patient, said DNase enzyme being administered in doses and regimens which are sufficient to decrease the average molecular weight of circulating extracellular blood DNA in the blood of said patient.

Abstract: Disclosed herein are embodiments for a novel method of producing an organic compound, including harvesting at least one organic compound from an organism or cell line genetically engineered with a gene for at least one proton-pump protein.

Abstract: Disclosed is a halogen-free high-frequency resin composition calculated according to parts by weight, and including 20-50 parts by weight of dicyclopentadiene epoxy resin, 10-40 parts by weight of styrene-maleic anhydride copolymer, 10-30 parts by weight of benzoxazine resin, 5-20 parts by weight of polyfunctional epoxy resin and 20-40 parts by weight of at least one phosphorus-containing flame retardant. A copper clad laminate made of the halogen-free high-frequency resin composition has excellent properties including a low dielectric constant, a low dielectric loss, a high heat resistance, a low water absorption, a low coefficient of expansion and a high PCB manufacturability.

Abstract: The invention relates to enzymes having xylanase, mannanase and/or glucanase activity, e.g., catalyzing hydrolysis of internal ?-1,4-xylosidic linkages or endo-?-1,4-glucanase linkages; and/or degrading a linear polysaccharide beta-1,4-xylan into xylose. Thus, the invention provides methods and processes for breaking down hemicellulose, which is a major component of the cell wall of plants, including methods and processes for hydrolyzing hemicelluloses in any plant or wood or wood product, wood waste, paper pulp, paper product or paper waste or byproduct. In addition, methods of designing new xylanases, mannanases and/or glucanases and methods of use thereof are also provided. The xylanases, mannanases and/or glucanases have increased activity and stability at increased pH and temperature.

Abstract: The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a hematopoietic cell.

Abstract: The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use 10 of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.

Abstract: The instant invention is based, at least in part, on the identification of novel methods for the enzymatic enrichment of capped RNAs. The invention provides, e.g., methods for enrichment of capped RNAs, kits for making such capped RNAs, and compositions of enriched RNAs or cDNA libraries derived therefrom.

Abstract: Fluorescent protein voltage sensors for measuring membrane potential and imaging high-frequency neuronal electrical activity are disclosed. In particular, the invention relates to engineered protein voltage sensors that comprise a voltage-sensing domain comprising four transmembrane domains linked to a circularly permuted fluorescent protein, which is inserted into the extracellular loop between the third (S3) and fourth (S4) transmembrane segments of the voltage-sensing domain. Such fluorescent protein voltage sensors can be used for measuring the electrical activity of neurons, including single action potentials, trains of action potentials, and subthreshold potential changes and, in particular, for imaging high-frequency neuronal electrical activity.

Abstract: This invention relates to phytases, polynucleotides encoding them, uses of the polynucleotides and polypeptides of the invention, as well as the production and isolation of such polynucleotides and polypeptides. In particular, the invention provides polypeptides having phytase activity under high temperature conditions, and phytases that retain activity after exposure to high temperatures. The phytases of the invention can be thermotolerant and/or thermostable at low temperatures, in addition to higher temperatures. The phytases of the invention can be used in foodstuffs to improve the feeding value of phytate rich ingredients. The phytases of the invention can be formulated as foods or feeds or supplements for either to, e.g., aid in the digestion of phytate. The foods or feeds of the invention can be in the form of pellets, liquids, powders and the like.

Abstract: Rationally-designed LAGLIDADG meganucleases and methods of making such meganucleases are provided. In addition, methods are provided for using the meganucleases to generate recombinant cells and organisms having a desired DNA sequence inserted into a limited number of loci within the genome, as well as methods of gene therapy, for treatment of pathogenic infections, and for in vitro applications in diagnostics and research.

Abstract: Endonucleases play an essential role in genetic engineering and molecular biology. A major barrier to the clinical adoption of nucleases and engineered nucleases remain the overall lack of specificity and activity. Off-site cleavage, cleavage at loci other than the target loci, typically occurs resulting in mutations, unexpected gene-knockouts, or translocations. Provided herein are systems and methods for identifying the off-site cleavage loci and predicting the activity of engineered endonucleases for a given genome. It is expected that these tools and methods will be useful for designing nucleases and other related DNA binding domains (e.g. TAL effectors) for genomic therapy and engineering.

Abstract: Compositions, methods and related uses are provided relating to cleaving modified DNA. For example, a set of DNA fragments obtainable by enzymatic cleavage of a large DNA is described where at least 50% are similarly sized and have a centrally positioned modified nucleotide. In addition, an enzyme preparation is provided that includes one or more enzymes that recognize a modified nucleotide in a DNA and cleave the DNA at a site that is at a non-random distance from the modified nucleotide. The one or more enzymes are further characterized by an N-terminal conserved domain with greater than 90% amino acid sequence homology to WXD(X)10YXGD. The related uses include creating a methylome, methods of purifying DNA fragments containing a modified nucleotide and diagnostic applications.

Abstract: The disclosure provides methods and compositions for generating conditional knock-out alleles using donor constructs together with sequence-specific nucleases to generate conditional knock-out alleles. Specifically, the donor construct comprises a 5? homology region, a 5? recombinase recognition site, a donor sequence, a 3? recombinase recognition site, and a 3? homology region. Further disclosed are the donor sequences each comprises a target sequence having at least one neutral mutation. Different sequence-specific nucleases can be used with the donor constructs are further disclosed.

Abstract: The present invention provides consumer products comprising a serine protease variant, more specifically subtilisin variants produced there from. Specifically, the present invention provides consumer products comprising a serine protease variant, more specifically a subtilisin variant having one or more substitutions as compared to a reference serine protease. In addition, the present invention provides methods of making such compositions and methods of treating surfaces, particularly fabric surfaces comprising contacting a surface with an aqueous liquor comprising a serine protease variant, more specifically subtilisin variants and an adjunct material.

Abstract: Compositions, methods, strategies, kits, and systems for the delivery of negatively charged proteins, protein complexes, and fusion proteins, using cationic polymers or lipids are provided. Delivery of proteins into cells can be effected in vivo, ex vivo, or in vitro. Proteins that can be delivered using the compositions, methods, strategies, kits, and systems provided herein include, without limitation, enzymes, transcription factors, genome editing proteins, Cas9 proteins, TALEs, TALENs, nucleases, binding proteins (e.g., ligands, receptors, antibodies, antibody fragments; nucleic acid binding proteins, etc.), structural proteins, and therapeutic proteins (e.g., tumor suppressor proteins, therapeutic enzymes, growth factors, growth factor receptors, transcription factors, proteases, etc.), as well as variants and fusions of such proteins.

Abstract: The present invention is directed to compositions and methods of preserving viability of islets of Langerhans for transplantation, and treating various disease and other abnormal or pathological conditions, including inflammatory bowel disease, ischemic heart disease, acute lung injury, acute respiratory distress syndrome and radiation-induced brain injury, with DNA repair enzymes that are directed to the mitochondria.

Abstract: The present invention provides autonomous replication sequences (ARSs) isolated from Nannochloropsis that support the replication of episomal DNA molecules (EDMs) in eukaryotic cells. The ARSs and EDMs provided herein can be used for expressing genes in organisms including algae and heterokonts.

Abstract: A method of using vaults as carrier molecules to deliver one or more than one substance to an organism, or to a specific tissue or to specific cells, or to an environmental medium. A vault-like particle. A method of preventing damage by one or more than one substance to an organism, to a specific tissue, to specific cells, or to an environmental medium, by sequestering the one or more than one substance within a vault-like particle. A method of delivering one or more than one substance or a sensor to an organism, to a specific tissue, to specific cells, or to an environmental medium. According to another embodiment of the present invention, there is provided a method of making vault-like particles, and making vault-like particles comprising one or more than one substance, or one or more than one sensor.

Abstract: The present invention relates to a method of producing a heterologous protein or polypeptide having phytase activity in a yeast system. The invention also provides proteins having phytase activity which have increased thermostability. Yeast strains which produce a heterologous phytase and the vectors used to produce the phytase are also provided.

Abstract: The present invention provides, among other things, compositions, kits and methods for subcutaneous delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention provides methods for treating Hunter syndrome by subcutaneous administration of a replacement iduronate-2-sulfatase (I2S) protein. In some embodiments, the present invention provides a kit comprising an arrangement of components for subcutaneously administering iduronate-2-sulfatase (I2S) protein.

Abstract: The present invention refers to methods for selectively recognizing a base pair in a DNA sequence by a polypeptide, to modified polypeptides which specifically recognize one or more base pairs in a DNA sequence and, to DNA which is modified so that it can be specifically recognized by a polypeptide and to uses of the polypeptide and DNA in specific DNA targeting as well as to methods of modulating expression of target genes in a cell.

Abstract: This disclosure describes genetically modified photosynthetic microorganisms, e.g., Cyanobacteria, that contain one or more exogenous genes encoding a phospholipase and/or thioesterase, which are capable of producing an increased amount of lipids and/or fatty acids. This disclosure also describes genetically modified photosynthetic microorganisms that contain one or more exogenous genes encoding a diacyglycerol acyltransferase, a phosphatidate phosphatase, and/or an acetyl-CoA carboxylase, which are capable of producing increased amounts of fatty acids and/or synthesizing triglycerides, as well as photosynthetic microorganism comprising mutations or deletions in a glycogen biosynthesis or storage pathway, which accumulate a reduced amount of glycogen under reduced nitrogen conditions as compared to a wild type photosynthetic microorganism.

Abstract: This disclosure relates to novel detergents for use in various procedures including, for example, nucleic acid amplification reactions such as polymerase chain reaction (PCR). Methods for preparing the modified detergents are also described.

Abstract: A HBS-specific antibody, a LHBS-specific antibody, a WT LHBS-specific antibody, an immunoassay kit comprising the antibodies, and a method of detecting pre-S2 deletion mutant LHBS using the immunoassay kit are disclosed herein. The method comprises incubating a biological sample with a first antibody to captured HBS proteins; detecting the LHBS and WT LHBS bound to the immobilized first antibody, respectively; and calculating the amount of the pre-S2 deletion mutant LHBS protein by subtracting the amount of the WT LHBS protein from that of the LHBS protein. Advantageously, by the method described herein, the amount of the pre-S2 deletion mutant LHBS, a potential high-risk marker for HCC incidence in chronic HBV carriers and recurrence in HCC patients after hepatectomy surgery, in a biological sample may be easily calculated without mutual influence between the WT and pre-S mutant LHBS while reducing the labor-intensive process for cloning each gene product before analysis.

Abstract: The present invention relates to the identification of novel nucleic acid sequences, designated herein as 7p, 8k, 7E, 9G, 8Q and 203, in a host cell which effect protein production. The present invention also provides host cells having a mutation or deletion of part or all of the gene encoding 7p, 8k, 7E, 9G, 8Q and 203, which are presented in FIG. 1, and are SEQ ID NOS.: 1-6, respectively. The present invention also provides host cells further comprising a nucleic acid encoding a desired heterologous protein such as an enzyme.

Abstract: Polynucleotide sequences are provided encoding a thermostable cellulase and directing its increased expression are provided, and the use of the thermostable cellulase in hydraulic fracturing methods and the treatment of flowback fluids.

Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of funcational effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases.

Abstract: High affinity SIRP-? reagent are provided, which (i) comprise at least one amino acid change relative to the wild-type protein; and (ii) have an increased affinity for CD47 relative to the wild-type protein. Compositions and methods are provided for modulating phagocytosis in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity SIRP? reagent, which blocks the physiological binding interaction between SIRP? and its ligand CD47.

Abstract: Low-copper click chemistry, 1.3-dipolar cycloadditions, and Staudinger ligations for modifying biomolecules is provided. Compositions, methods, and kits relating to low-copper click chemistry, 1.3-dipolar cycloadditions, and Staudinger ligations are also provided.

Abstract: Disclosed herein are compositions for linking DNA binding domains and cleavage domains (or cleavage half-domains) to form non-naturally occurring nucleases. Also described are methods of making and using compositions comprising these linkers.

Abstract: Provided herein are methods and compositions for treating a subject suffering from a deficiency in arylsulfatase A in the CNS. The methods include systemic administration of a bifunctional fusion antibody comprising an antibody to a human insulin receptor and an arylsulfatase A.

Abstract: A method of gene editing or gene stacking within a FAD3 loci by cleaving, in a site directed manner, a location in a FAD3 gene in a cell, to generate a break in the FAD3 gene and then ligating into the break a nucleic acid molecule associated with one or more traits of interest is disclosed.

Abstract: The present invention relates to nucleic acids sequences derived from Valeriana officinalis and/or Persicaria hydropiper and encoding drimenol synthase polypeptides. The present invention also provides the amino acid sequences of the polypeptides. The invention further provides host cells or organisms genetically modified to harbour the polynucleotides of the invention. A method to produce drimenol and/or a drimenol derivative by contacting farnesyl diphosphate with a polypeptide having a drimenol synthase activity is also part of this invention.

Abstract: A class of anionic oligomers and polymers that function for inhibition of nucleases, particularly RNase. Specific inhibitors include mixtures of oligomers of vinyl sulfate. Methods for inhibition or inactivation of one or more nucleases in vitro which comprises the step of contacting the one or more nucleases in a biological medium with one or more of the anionic oligomeric or polymeric inhibitors of this invention. Kits for carrying out a biological procedure, biological reaction and/or a biological assay containing one or more inhibitors of this invention. The use of oligomers and/or polymers of this invention as additives in buffers or reagents. The inhibitors of the invention can also be attached to surfaces to provide for removal of nucleases from media, solutions or other liquids in contact with the solid.