Abstract: Improved compositions and methods for treating muscular dystrophy by administering antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping are described.

Abstract: The present invention relates to treatment of inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) using antisense nucleotides that are directed against polymorphic forms (e.g., those containing single nucleotide polymorphisms) of the SMAD7 mRNA. The invention thus relates to treatment methods for subjects having polymorphic forms of SMAD7 and antisense oligonucleotides that specifically target SMAD7 mRNA transcripts containing polymorphisms.

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: A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5? terminal side of the region, (c) one or more nucleotide analogs located on 3? terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides.

Abstract: The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

Abstract: The present invention relates to a method for predicting the progression of chronic kidney disease (CKD) in a patient and also to an inhibitor of NGAL gene expression or an NGAL antagonist for use in the prevention or the treatment of CKD.

Abstract: The invention provides a single-stranded nucleic acid molecule of (A) or (B) containing a TGF-?1 gene expression inhibitory sequence. The single-stranded nucleic acid molecule (A) consists of region (Xc), linker region (Lx) and region (X) from the 5?-side to the 3?-side, wherein linker region (Lx) has a non-nucleotide structure containing at least one of a pyrrolidine skeleton and a piperidine skeleton, and at least one of region (X) and region (Xc) contains the expression inhibitory sequence.

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ANGPTL3 gene, as well as methods of inhibiting expression of ANGPTL3 and methods of treating subjects having a disorder of lipid metabolism, such as hyperlipidemia or hypertriglyceridemia, using such dsRNA compositions.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Fibroblast growth factor 21 (FGF21), in particular, by targeting natural antisense polynucleotides of Fibroblast growth factor 21 (FGF21). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of FGF21.

Abstract: The invention provides a method and composition for the treatment, prevention, and diagnosis of cancer containing or derived from cancer stem cells.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of RNase H1, in particular, by targeting natural antisense polynucleotides of RNase H1. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of RNASE H1.

Abstract: The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids comprising at least one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

Abstract: The present invention encompasses a class of compounds known as splice modulating oligonucleotides (SMOs) that modulate pre-mRNA splicing, thereby affecting expression and functionality of a specific protein in a cell. The present invention further provides compositions and methods for modulating pre-mRNA splicing using a SMO of the invention to abrogate disease-causing mutations in a protein. Accordingly, the present invention provides compositions and methods of treating a subject at risk of, susceptible to, or having a disease, disorder, or condition associated with aberrant or unwanted target pre-mRNA expression or activity.

Abstract: The present disclosure provides a pharmaceutical composition for treating cancer comprising an RNA oligonucleotide having a particular sequence and structure. Specifically, when a cell line is treated with an RNA oligonucleotide having specific sequence and helical bend structure according to the present disclosure, the expression of ISG56 is increased and apoptosis of cancer cells is induced. Thus, a composition comprising the RNA oligonucleotide can be used as an anticancer agent.

Abstract: A method of stimulating a TLR9-activated immune response or enhancing a TLR9-activated immune response to an antigen is disclosed herein. TLR9 is the cellular receptor for CpG-ODN, and current developed CpG-ODN has low activity to rabbit TLR9. Here, the method of stimulating TLR9-activated immune response by administering an effective amount of immunogenic composition comprising an antigen and a CpG-ODN comprising GACGTT or AACGTT motif was demonstrated to have potent immunostimulatory activity to rabbit TLR9, and capable of boosting a less toxic and potent antibody response in rabbits.

Abstract: The present disclosure discloses an asparaginase mutant with efficient expression, activity and stability, belonging to the technical fields of gene engineering and enzyme engineering. The amino acid sequence of the asparaginase mutant is set forth in SEQ ID NO: 99, SEQ ID NO: 100 or SEQ ID NO: 101; meanwhile, compared with the wild type asparaginase mutant, the extracellular enzyme activity of the asparaginase fusion enzyme mutant is increased by up to 2.25 times, the stability is increased by up to 3.56 times, and the specific enzyme activity is increased by up to 1.34 times.

Abstract: Fungal artificial chromosome (FAC) vectors are disclosed. A vector can be replicated in a bacterial or a fungal host, and can comprise an insert of heterologous DNA up to about 500 kilobases. A vector can be used for cloning and expressing a secondary metabolite (SM) gene cluster. An insert sequence can be modified by homologous recombination. A vector can be a plasmid comprising bacterial and fungal origins of replication, as well as bacterial and fungal selection marker genes. Also disclosed are vectors that can be integrated into a fungal genome, and dual function vectors which can be replicated in a bacterial or a fungal host and can also be integrated into a fungal genome. Also disclosed are methods of generating plasmid libraries including vectors comprising intact SM gene clusters.

Abstract: Plant metabolism and alkaloid levels can be regulated by transcription factors that regulate the nicotinic alkaloid biosynthetic pathway. In one embodiment, the disclosure provides a transcription factor that negatively regulates alkaloid biosynthesis, such as nicotine biosynthesis.

Abstract: This invention relates to the expression a DA1 protein with a mutation that disrupts or inactivates the LIM domain or the LIM-like domain within cells of a plant. This may increase the yield or enhance a yield-related trait of the plant. Methods, plants and plant cells are provided.

Abstract: The invention provides methods and materials for increasing root biomass in a plant, by increasing the expression of at least one PEAPOD protein, or fragment thereof, in the plant. The invention also provides methods and materials for producing a plant increased root biomass, the method comprising the step of increasing the expression of at least one PEAPOD protein, or fragment thereof, in the plant.

Abstract: Provided are isolated polypeptides which are at least 80% homologous to SEQ ID NOs: 710-1153 and 9276-15726, isolated polynucleotides which are at least 80% identical to SEQ ID NOs: 1-709 and 1157-9275, nucleic acid constructs comprising same, transgenic cells expressing same, transgenic plants expressing same and method of using same for increasing yield, abiotic stress tolerance, growth rate, biomass, vigor, oil content, photosynthetic capacity, seed yield, fiber yield, fiber quality, fiber length, and/or nitrogen use efficiency of a plant.

Abstract: A transgenic plant having enhanced photosynthesis is disclosed. The transgenic plant is transformed with a transgenic polynucleotide encoding a heterologous bicarbonate transporter. The bicarbonate transporter can be from an algae or a cyanobacterial species. The transgenic polynucleotide comprises a nucleic acid sequence encoding the bicarbonate transporter under the control of a functional plant promoter and optionally includes a chloroplast envelope targeting peptide heterologous to the bicarbonate transporter. Methods of making the transgenic plant and transgenic polynucleotide are disclosed.

Abstract: Disclosed herein are the nucleotide sequences of the Chromobacterium subtsugae genes. In addition, the amino acid sequences of proteins encoded by the C. subtsugae genes are provided. Nucleic acids, vectors and polypeptides comprising the aforementioned sequences are also provided. Homologues, functional fragments and conservative variants of the aforementioned sequences are also provided. Compositions having pesticidal, bioremedial and plant growth-promoting activities comprising C. subtsugae genes and proteins, and methods for the use of these compositions, are also provided.

Abstract: Compositions and methods for controlling pests are provided. The methods involve transforming organisms with a nucleic acid sequence encoding an insecticidal protein. In particular, the nucleic acid sequences are useful for preparing plants and microorganisms that possess insecticidal activity. Thus, transformed bacteria, plants, plant cells, plant tissues and seeds are provided. Compositions are insecticidal nucleic acids and proteins of bacterial species. The sequences find use in the construction of expression vectors for subsequent transformation into organisms of interest, as probes for the isolation of other homologous (or partially homologous) genes. The insecticidal proteins find use in controlling, inhibiting growth or killing lepidopteran, coleopteran, dipteran, fungal, hemipteran, and nematode pest populations and for producing compositions with insecticidal activity.

Abstract: A method for preventing or treating cardiomyopathy due to energy failure in a subject in need thereof is provided. The method comprises administering to the subject a therapeutically effective amount of a vector which comprises a nucleic acid sequence encoding a gene that can reverse energy failure. An exemplary cardiomyopathy is that which is associated with Friedreich ataxia and an exemplary nucleic acid sequence comprises a nucleic acid that encodes frataxin (FXN).

Abstract: Disclosed herein are nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Disclosed herein are engineered non-naturally occurring nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Targetable nuclease systems can be used to edit genetic targets, including recursive genetic engineering and trackable genetic engineering methods.

Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Abstract: A method for producing metal chalcogenide nanoparticles, the method comprising: (i) producing hydrogen chalcogenide-containing vapor from a microbial source, wherein said microbial source comprises: (a) chalcogen-reducing microbes capable of producing hydrogen chalcogenide vapor from a chalcogen-containing source; (b) a culture medium suitable for sustaining said chalcogen-reducing microbes; (c) at least one chalcogen-containing compound that can be converted to hydrogen chalcogenide vapor by said chalcogen-reducing microbes; and (d) at least one nutritive compound that provides donatable electrons to said chalcogen-reducing microbes during consumption of the nutritive compound by said chalcogen-reducing microbes; and (ii) directing said hydrogen chalcogenide-containing vapor into a metal-containing solution comprising a metal salt dissolved in a solvent to produce metal chalcogenide nanoparticles in said solution, wherein said chalcogen is sulfur or selenium, and said chalcogenide is sulfide or selenide, res

Abstract: Provided herein is an isolated polypeptide from Juniperus virginiana, Platycladus orientalis ‘Beverleyensis’ or Platycladus orientalis comprising a (+)-cedrol or a (?)-thujopsene synthase. Further provided herein is an isolated nucleic acid molecule from Juniperus virginiana, Platycladus orientalis ‘Beverleyensis’ or Platycladus orientalis encoding a (+)-cedrol or (?)-thujopsene synthase. Further provided herein are methods of producing (+)-cedrol or (?)-thujopsene.

Abstract: Provided are genetically engineered microorganism that catalyze the synthesis of propane and/or butanol from a suitable substrate such as glucose. Also provided are methods of engineering said genetically engineered microorganism and methods of producing propane and/or butanol using the genetically engineered microorganism.

Abstract: Disclosed are methods for the synthesis of chiral alcohols by Sortase A-mediated oxidoreductase oligomers, which relates to the field of biocatalysis. In the present disclosure, oxidoreductase oligomers were used as biocatalysts for chiral alcohol preparation. Compared to wild-type enzymes, the oxidoreductase oligomers significantly improved catalytic activity and thermal stability. The sortase A-mediated oxidoreductase oligomers had 6-8 folds improvement in specific activity over that of the wild-type enzymes. The oligomers displayed a Tm value 6-12° C. higher than that of the wild-type, suggesting the sortase A-mediated oxidoreductase oligomers significantly improved thermostability of the enzymes. The oxidoreductase oligomers catalyzed asymmetric transformation to produce (S)-1-phenyl-1,2-ethanediol or (R)-1-phenethyl alcohol within 3-6 hr, with an optical purity of 98%-100% and a yield of 98%-99%.

Abstract: This disclosure relates to compositions and methods for converting biomass to various chemical intermediates and final products including fuels. Aspects include the depolymerization of lignin, cellulose, and hemicellulose to a wide slate of depolymerization compounds that can be subsequently metabolized by genetically modified bacterium, and converted to cis,cis-muconic acid. Other aspects include the use of monometallic catalysts for converting the cis,cis-muconic acid to commodity chemicals and fuels, for example adipic acid and/or nylon.

Abstract: The present invention provides a fed-batch culture method comprising a step of fed-batch-feeding a carbon source base and a base in such a manner that the pH level can be maintained at a level suitable for the growth of microorganisms for fermentation of a carbon source. The present invention also provides a method for preparing organic acids using the fed-batch culture method. The present invention fed-batch-feeds a neutralizing agent such as ammonium bicarbonate, ammonium carbonate or alkali metal-containing weak base, and a carbon source substrate in preparing organic acids by microorganism fermentation. Thus, a pH level suitable for the survival of microorganisms for carbon source fermentation can be maintained, and the speed of injecting the carbon source base which is the source material can be appropriately adjusted.

Abstract: Processes for starting up and operating anaerobic, deep tank fermentation reactors including a process for anaerobic bioconversion of a gas substrate comprising carbon monoxide, hydrogen, and carbon dioxide in a reactor by contact of the gas substrate with an aqueous menstruum containing microorganisms suitable for converting the gas substrate to an oxygenated organic compound in the reactor. The process further includes: blanketing the reactor above the aqueous menstruum to the essential exclusion of oxygen with a head space gas comprising at least one of carbon monoxide, hydrogen, carbon dioxide, nitrogen, and a lower alkane; continuously supplying a feed gas comprising at least a portion of the gas substrate to the aqueous menstruum in the reactor; and injecting the gas substrate and a motive liquid into the reactor to form a dispersion of the motive liquid and microbubbles, the microbubbles having a diameter of less than about 500 microns.

Abstract: A method of producing lipids, containing the steps of: culturing a transformant in which the expression of a gene encoding the following protein (A) or (B) is enhanced, and producing long-chain fatty acids or the lipids containing these fatty acids as components, wherein: protein (A) is a protein consisting of the amino acid sequence set forth in SEQ ID NO: 1; and protein (B) is a protein consisting of an amino acid sequence having 70% or more identity with the amino acid sequence of the protein (A), and having ?-ketoacyl-ACP synthase activity.

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 fatty acid or fatty acid derived product, wherein the modified microorganism produces fatty acyl-CoA intermediates via a malonyl-CoA dependent but malonyl-ACP independent mechanism.

Abstract: The invention relates to a novel process for the preparation of chiral 2-(4-aminophenyl) morpholines of the formula wherein R1 is hydrogen an amino protecting group. The chiral 2-(4-aminophenyl) morpholines of the formula I are key intermediates for the preparation of compounds that have a good affinity to the trace amine associated receptors (TAARs).

Abstract: The invention relates to a process for the preparation of a fermentation product from lignocellulosic material, comprising the following steps: a) optionally, pretreatment of the lignocellulosic material, b) optionally, washing of the optionally pretreated lignocellulosic material, c) enzymatic hydrolysis of the optionally washed and/or optionally pretreated lignocellulosic material using an enzyme composition comprising at least two cellulases and whereby the enzyme composition at least comprises LPMO, and optionally purifying the hydrolysed lignocellulosic material, d) fermentation of the hydrolysed lignocellulosic material to produce a fermentation product, and e) optionally, recovery of a fermentation product, wherein the amounts of formed hydrolysed oxidation products at the end of the enzymatic hydrolysis by the oxidation by LPMO of the lignocellulosic material containing cellulose and/or cello-oligosaccharides is kept between 3 to 80 g/kg glucan present in the lignocellulosic material by adding a s

Abstract: The present invention relates to a method of making glucose syrup from liquefied starch comprising, (a) contacting the liquefied starch with a glucoamylase, a pullulanase, and optionally an alpha-amylase wherein the ratio of pullulanase dose expressed as NPUN/gDS, to alpha-amylase dose expressed as FAU(A)/gDS is at least 60, particularly at least 75, particularly at least 100, more particularly at least 150, more particularly at least 200, more particularly at least 250, more particularly at least 300, more particularly at least 400, more particularly at least 500, more particularly at least 600, more particularly at least 800 or if no alpha-amylase is present the pullulanse is present in a dose of at least 0.5, particularly at least 0.75, particularly at least 1.0, particularly at least 1.5 NPUN/gDS, and (b) saccharifying the liquefied starch.

Abstract: Methods are disclosed for the enzymatic preparation of galactooligosaccharide (GOS) from lactose using two different microbial lactase enzymes to maximize the extent of transgalactosylation during the digestion of lactose. Methods are also disclosed for avoiding the turbidity of a solution comprising GOS and lactose as it is adjusted for incubation with a yeast neutral lactase.

Abstract: The present disclosure relates to recombinant microorganisms engineered for enhanced production of a desired carbohydrate, as well as related biomass, and compositions which are useful, inter alia, as animal feed ingredients. The present disclosure also provides related methods.

Abstract: Vectors expressing kanA-kanB-kanK and other kanamycin production-related genes, Streptomyces species recombinant bacteria transformed with the vectors, a method of producing kanamycin antibiotics by the bacteria, and a new kanamycin compound produced by the bacterium are provided. With the use of the recombinant bacteria of the present invention, the direct fermentative biosynthesis of amikacin and tobramycin as semi-synthetic kanamycins is possible, and the yield of kanamycin B as a precursor of the semi-synthetic kanamycin is improved.

Abstract: The invention provides means and methods for producing one or more Ig-like molecules in a single host cell. Novel CH3 mutations enabling the production of monospecific and/or bispecific Ig-like molecules of interest are also provided.

Abstract: Systems, methods, and apparatus for determining whether a culture in a vessel contains a plurality of microorganisms are provided. A normalization relative value is calculated for each respective measurement of a biological state of the culture between (i) the respective measurement and (ii) an initial biological state. For each fixed interval of time points, a derivative of the normalization relative values in the interval of time points is calculated, thereby forming a plurality of rate transformation values. For each set of rate transformation values in the plurality of rate transformation values, a measure of central tendency of the values in the set is computed, thereby forming a plurality of average relative transformation values. A determination whether the culture contains the microorganisms is made based on whether any calculated average relative transformation value exceeds a first threshold or whether an extent of growth exhibited by the culture exceeds a second threshold.

Abstract: A multiplex hand-held diagnostic biosensor, using two inflammatory salivary biomarkers, Human Neutrophil Elastase (HNE) and Cathepsin-G, was constructed made to potentially detect Periodontitis at an early stage is described. The use of magnetic nanoparticle biosensor method used as a device was based on the measurement of proteolytic activity using specific proteases probes. The magnetic nanoparticle biosensor device is capable of specific and quantitative detection of HNE and Cathepsin-G in solution and in spiked saliva samples with a lower detection limit of 1 pg/mL and 100 fg/mL for HNE and Cathepsin-G, respectively.

Abstract: The present invention concerns diagnostic methods for coagulation testing involving determining anticoagulant activity elicited by a first anticoagulant in a sample comprising measuring a first Factor Xa activity in a body fluid test sample of said subject, measuring a second Factor Xa activity in at least one calibrator sample comprising a predefined anticoagulation activity for a second anticoagulant, calculating an universal parameter for the anticoagulation activity comprised in the test sample based on the first and the second measured Factor Xa activities and comparing the said parameter for the anticoagulation activity with predefined ranges of expected anticoagulation activity for at least three anticoagulants. Further provided is a computer program code assisting the method as well as a system for carrying out the said method as well as a kit.

Abstract: The present invention provides a method of determining whether cytosine residues present at a predetermined positions within a single strand of a double stranded DNA of known sequence are methylated as well as compounds for carrying out this method.

Abstract: The invention relates to methods, compositions, devices, systems and kits as described including, without limitation, reagents and mixtures for determining the identity of nucleic acids in nucleotide sequences using, for example, sequencing by synthesis methods. In particular, the present invention contemplates the use of polyphenolic compounds, known as antioxidant additives, to improve the efficiency of Sequencing-By-Synthesis reactions. For example, gallic acid (GA) is shown herein to be one of many exemplary SBS polyphenolic additives.

Abstract: The present disclosure provides methods for detecting a single-stranded target RNA. The present disclosure provides methods of cleaving a precursor C2c2 guide RNA array into two or more C2c2 guide RNAs. The present disclosure provides a kit for detecting a target RNA in a sample.

Abstract: The present invention relates to a method for detecting single nucleotide polymorphism (SNP) using a feature that the 5?-flap endonuclease (FEN) activity of DNA polymerase is inhibited when a probe complementarily binds to the end of a polymerase chain reaction (PCR) product. More specifically, the present invention relates to a novel method wherein it was verified that, when a probe used for a real-time PCR complementarily binds to the end site of a PCR product, the 5?-FEN activity of thermostable DNA polymerase to the probe is inhibited, and thus when such a feature is used to make a design such that an SNP site to be detected is located at the 5?-end site of the probe, the 5?-flap formation is induced according to the allele, thereby allowing effective SNP detection.