Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain or a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.

Abstract: Polypeptides having endoglucanase activity, catalytic domains, and polynucleotides encoding the polypeptides or catalytic domains. Nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides or catalytic domains.

Abstract: A method for mass production of human coagulation factor VII derivatives. The method employs an expression vector, containing i) a nucleotide sequence of DHFR promoter devoid of at least one CCGCCC repeat sequence from the GC-rich region thereof and a nucleotide sequence encoding a DHFR operably linked thereto, and ii) a nucleotide sequence of CMV early gene promoter and a nucleotide sequence encoding a human coagulation factor VII derivative operably linked thereto; and adds at least one selected from the group consisting of sodium butyrate, vitamin K, and a culture medium supplement.

Abstract: Embodiments of the present disclosure provide for nanozymes that can include a therapeutic agent, methods of making nanozymes, methods of using nanozymes, and the like.

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 are rapid and reproducible methods for separating and purifying nucleic acids from paraffin-containing tissue samples. The disclosed methods involve a melting step, where paraffin-containing tissue samples are heated in the presence of a detergent, causing the paraffin to melt and tissue sample cells to lyse. From the resulting two-phase mixture (i.e., a paraffin phase and an aqueous phase), the aqueous phase is collected for purification of nucleic acid. Protease(s) can be used at one or more points in the separation process to facilitate tissue cell lysis and/or degrade proteins that could degrade nucleic acid or interfere with subsequent genetic manipulation or analysis.

Abstract: A method for synthesizing an antiserum for rapid-turnaround therapies includes collecting antibody-secreting cells from a test subject, wherein the test subject has been exposed to a target biological agent and has produced an antibody response; selecting a subset of the antibody-secreting cells, the subset of the antibody-secreting cells producing antibodies that neutralize the target biological agent; generating variable-region-coding DNA sequences from the antibodies that neutralize the target biological agent; tagging amplicons of the variable-region-coding DNA sequences with unique nucleic acid identifiers to associate the variable-region-coding DNA sequences derived from individual ones of the subset of the antibody-secreting cells; analyzing antibody-type distribution in a natural immune response; synthesizing antibodies from the variable-region-coding DNA sequences to form synthetic antibodies; and mixing the synthetic antibodies in a proportion equal to the antibody-type distribution in the natural i

Abstract: Provided herein is a method for fabricating transformable or transfectable molecules that includes an assembly reaction containing a variety of pre-made cassettes possessing ends that hybridize to one another, transforming or transfecting said molecules into a desired host cell and then selecting a transformed/transfected host cell containing plasmid molecules composed of said the cassettes. A kit for performing the method is also provided.

Abstract: Disclosed herein are therapeutic methods for treating lung diseases, disorders and injury in a mammal, including treatment of acute respiratory distress syndrome (ARDS), acute lung injury, pulmonary fibrosis (idiopathic), bleomycin induced pulmonary fibrosis, mechanical ventilator induced lung injury, chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, bronchiolitis obliterans after lung transplantation and lung transplantation-induced acute graft dysfunction, including treatment, prevention or prevention of progression of primary graft failure, ischemia-reperfusion injury, reperfusion injury, reperfusion edema, allograft dysfunction, pulmonary reimplantation response, bronchiolitis obliterans after lung transplantation and/or primary graft dysfunction (PGD) after organ transplantation, in particular in lung transplantation, comprising down-regulating the TLR2 gene or both the TLR2 gene and TLR4 gene.

Abstract: The present invention relates to method, system, and composition for modulating the compliance of the trabecular meshwork, which may provide treatment to glaucoma.

Abstract: This invention provides compositions and methods for preventing or treating a malignant tumor in a mammal in need thereof, by administering to the mammal a therapeutically effective amount of a composition comprising RNAi molecules, which RNAi molecules can be active in reducing expression of Hsp47, or a combination of RNAi molecules active for Hsp47 and p21.

Abstract: The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.

Abstract: The disclosure relates to compositions comprising a HBV RNAi agent. In some embodiments, the HBV RNAi agent comprises a sense and an anti-sense strand, each strand being an 18-mer and the strands together forming a blunt-ended duplex, wherein the 3? end of at least one strand terminates in a phosphate or modified internucleoside linker and further comprises, in 5? to 3? order: a spacer; a second phosphate or modified internucleoside linker; and a 3? end cap. In some embodiments, the 3? end of both the sense and anti-sense strand further comprise, in 5? to 3? order: a spacer; a second phosphate or modified internucleoside linker; and a 3? end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3? end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker.

Abstract: Methods of modulating the occurrence of lymphangiogenesis in a subject are provided. In some instances, the method includes reducing antigen presenting cell function, such as cell trafficking to draining lymph nodes. In some instances, the method includes treating corneal transplant rejection in the subject. Aspects of the methods include administering to the subject an effective amount of an antagonist of angiopoietin-2 (Ang-2) to reduce the occurrence of lymphangiogenesis. In some cases, the method results in the improvement of graft survival in the subject. Also provided are methods of reducing immune cell activity in a sample, e.g., reducing antigen presenting cell trafficking to draining lymph nodes. Also provided are compositions, e.g., ophthalmic pharmaceutical compositions and kits that find use in the subject methods.

Abstract: The present invention relates to dsRNA molecules for inhibiting the expression of CYP51 gene(s) from a fungal or oomycete phytopathogen and the use of such inhibitory dsRNA molecules for controlling phytopathogenic fungi and/or oomycetes. The present invention further relates to DNA sequences providing a transcriptional template for inhibitory dsRNA molecules or antisense RNA; and phytopathogen-tolerant transgenic plants with such DNA sequences.

Abstract: The invention relates to nucleic acids and methods for restoring acid alpha-glucosidase (GAA) activity in patients with Pompe disease using splice-switching technology.

Abstract: The present invention is related to a nucleic acid molecule comprising a double-stranded structure, wherein the double-stranded structure is formed by a first strand and a second strand, wherein the first strand consist of the following nucleotide sequence 5? acGaGcUgGaCcAcUgGuCdTsdT 3?, and the second strand consists of the following nucleotide sequence 5? GAcCaGuGgUcCaGcUcGudTsdT 3?, wherein a minor nucleotide indicates that the nucleotide is 2?-F modified and an underlined nucleotide indicates that the nucleotide is 2?-0-methyl modified and wherein dTsdT indicates that at the 3? end a dinucleotide is attached consisting of two dT nucleotides, wherein said two dTs are covalently linked through a phosphorothioate bond.

Abstract: This invention provides oligomer structures for therapeutic agents, the oligomers composed of one or more UNA nucleomonomers, along with nucleic acid monomers. The UNA oligomers may be used as therapeutic agents for treating or preventing disease. The UNA oligomers can be capable of modulating or silencing gene expression, through RNA interference or other modalities, and may have an antisense strand and a sense strand.

Abstract: A genetic screen for Arabidopsis mutants displaying a hyper-susceptible to Agrobacterium transformation (hat) phenotype was performed. The gene disrupted in the hat3 mutant encodes a putative myb-family transcription factor (MTF) that negatively regulates susceptibility to Agrobacterium-mediated transformation. Over-expression of an integrin-like protein results in plants that are hyper-susceptible to transformation. Manipulation of MTF, members of this protein family, and members of the integrin domain-like protein family for example At14a allows improved control of Agrobacterium transformation, including in crops.

Abstract: The present invention provides methods and compositions for regulation of gene expression in plants. In particular, the invention provides nucleic acids that can confer tissue specific and constitutive expression to operably linked polynucleotides of interest.

Abstract: The present invention relates to the production and use of covalently closed circular (ccc) recombinant DNA molecules such as plasmids, cosmids, bacterial artificial chromosomes (BACs), bacteriophages, viral vectors and hybrids thereof, and more particularly to vector modifications that improve expression of said DNA molecules.

Abstract: An object is to develop a technology enabling utilization, by only an extremely simple technique, of a technology which is widely applicable to mammals without requiring the utilization of an ES cell, and which involves modifying a certain gene by targeting a certain sequence on a genome (genome editing technology based on ZFN or the like). Provided is a technology for efficiently modifying an arbitrary target gene of a mammal, by immersing a pronuclear stage mammalian zygote with an intact zona pellucida into a solution containing a pair of molecules of mRNA having a certain sequence, and performing electroporation treatment through application of multiple square-wave pulses in three steps with the total electric energy of a first electric pulse adjusted within a predetermined range.

Abstract: Described herein are methods of expressing nucleic acids in T cells pre-exposed to a co-stimulatory signal and then transduced with adenoviral vectors. In some embodiments, the co-stimulation is provided by anti-CD3 and anti-CD28 antibodies and the adenoviral vector is pseudotyped for T-cell entry. The invention also relates to compositions for carrying out these methods, provided as kits or pharmaceutical compositions that can be used to treat diseases including immunological conditions and hematological malignancies.

Abstract: An expression method of active goldfish gfTP1 transposase protein comprises: constructing an expression vector comprising a gfTP1 transposase reading frame of a goldfish Tgf2 transposon, after transferred into escherichia coli Rosetta 1(DE3), culturing an expression strain until absorbance of a bacteria solution under OD600 reaches 0.3-0.4, adding IPTG, culturing under 21-22° C. in shaking of 150-200 rpm, inducing to express soluble recombinant protein, and purifying to obtain a functionally active transposase. Also provided are an expression plasmid and the expression strain of the goldfish gfTP1 transposase protein, and a use of the strain in transgenosis.

Abstract: The present disclosure provides DNA-guided CRISPR systems; polynucleotides comprising DNA, RNA and mixtures thereof for use with CRISPR systems; and methods of use involving such polynucleotides and DNA-guided CRISPR systems.

Abstract: Methods and compositions for producing a sesquiterpene alcohol comprising contacting a sesquiterpene with a p450 polypeptide with monooxygenase activity.

Abstract: The present invention relates to a reaction mixture and a method of producing at least one higher alcohol comprising a reaction mixture comprising a mixed culture of a first and a second microorganism in an aqueous medium comprising carbon monoxide gas, wherein the first microorganism is an acetogenic microorganism capable of converting a carbon source to acetate and/or ethanol; and the second microorganism is selected from the group consisting of Clostridium kluyveri, and C. Carboxidivorans capable of converting the acetate and/or ethanol to form an acid; wherein the first microorganism is further capable of converting the acid to the corresponding higher alcohol and the higher alcohol comprises at least 6 carbon atoms.

Abstract: Providing a microbial catalyst in a reaction broth, providing an adsorptive solid into the reaction broth, providing a producer gas into the reaction broth, and obtaining a fermentation product from the reaction broth resulting from activity of the microbial catalyst in the presence of the adsorptive solid.

Abstract: A reaction mixture for producing ethanol and/or acetate from a carbon source in aerobic conditions, wherein the mixture comprises a first acetogenic microorganism in an exponential growth phase; free oxygen; and a second acetogenic microorganism in a stationary phase wherein the first and second acetogenic microorganism is capable of converting the carbon source to the acetate and/or ethanol.

Abstract: The present disclosure provides methods of fermenting a lignocellulosic biomass, wherein a nucleophile is added to deactivate carbonyl-containing fermentation inhibitors in hydrolysate formulated by pretreating the lignocellulosic biomass. The disclosure also provides methods of fermenting a lignocellulosic biomass, wherein a nucleophile is added to deactivate carbonyl-containing fermentation inhibitors in a slurry formulated by pretreating the lignocellulosic biomass.

Abstract: Methods for producing glycosylated and methylated resveratrol in a genetically engineered cell, by bioconversion, and in vitro are disclosed herein.

Abstract: There is provided a method for generating an oil/fat component, in which salt-tolerant algae are cultured in a culture medium of which the salt concentration has been increased in a stepwise manner.

Abstract: The present invention provides for a genetically modified yeast host cell capable of producing one or more fatty acids, or fatty acid-derived compounds, or a mixture thereof, comprising: (a) increased expression of acetyl-CoA carboxylase (such as ACC1), (b) increased expression of one or more fatty acid synthases (such as FAS1 and FAS2), and (c) optionally reduced expression of one or more enzymes involved in or in the ?-oxidation pathway (such as peroxisomal transporters PXA1 and PXA2, and ?-oxidation enzymes POX1, POX2, and POX3).

Abstract: The present disclosure relates to an engineered microbe capable of improved productivity of fatty acid or fatty acid derivative. An NAD+-dependent 3-oxoacyl-ACP reductase or NAD+-dependent 3-oxoacyl-CoA reductase replaces or supplements the native NADP+-dependent 3-oxoacyl-ACP reductase so as to utilize the higher availability of NAD+ rather than NADP+ in the cell. Higher production, yield and titer of fatty acids are therefore obtained. Such microbes can be combined with other mutations to further improve yield of fatty acids or fatty acid derivatives.

Abstract: A process for removing sulphide from an aqueous solution comprising sulphide is disclosed, in which the aqueous solution is subjected to sulphide-oxidising bacteria in the presence of oxygen in a reactor to oxidise sulphide to elemental sulphur. According to the process, a molecular-oxygen containing gas is supplied to a reactor containing the sulphide-oxidising bacteria in an aqueous medium, such that one or more aerated zones and one or more non-aerated zones are created in the aqueous medium with upward liquid flow in the aerated zones and downward liquid flow in the non-aerated zones; and a feed stream of the aqueous solution comprising sulphide is injected into the reactor in the one or more non-aerated zones, wherein the one or more aerated zone(s) are not separated from the one or more non-aerated zone(s) by means of vertically extending reactor internal.

Abstract: An isolated protein or peptide, which is functional for a partial synthesis step of the biosynthesis of [S,S]-ethylenediamine-disuccinate, including or composed of an amino acid sequence selected from the group consisting of SEQ ID No. 39, SEQ ID No. 41, SEQ ID No. 43, SEQ ID No. 45, SEQ ID No. 47, SEQ ID No. 49, SEQ ID No. 51, SEQ ID No. 53, and combinations thereof.

Abstract: Various systems and methods are provided for converting lignocellulosic biomass to concentrated sugars. For example, a saccharification process includes obtaining lignocellulosic biomass and converting the lignocellulosic biomass into sugars. The lignocellulosic biomass is converted into sugars by flowing the lignocellulosic biomass countercurrently to a flow of water through a saccharification vessel having a column and converting the lignocellulosic biomass into a sugar solution using an enzyme in the column.

Abstract: The present invention is directed to a process for the hydrolysis of biomass as well as the saccharide-containing permeate product and the protein-containing product produced by this process. In a further aspect, the present invention is directed to a process for the production of organic compounds from the saccharide-containing product. In an additional aspect the present invention is directed to the use of the protein-containing product for the production of a fermentation medium.

Abstract: The invention relates to methods of saccharifying a cellulosic material comprising subjecting the cellulosic material to a catalase and a cellulolytic enzyme composition comprising a GH61 polypeptide in the presence of dissolved oxygen at a concentration of greater than 10% of the saturation level. The invention also related to methods of producing desired fermentation products, such as ethanol, using a method including a saccharification step of the invention.

Abstract: The application discloses a method for producing an oligosaccharide of at least four monosaccharide units, advantageously an HMO, particularly an HMO of only four monosaccharide units, said method comprising a step of: culturing, in a culture medium containing a fucosylated, sialylated or N-acetyl-glucosaminylated lactose trisaccharide as acceptor, a genetically modified cell having a recombinant gene that encodes an enzyme capable of modifying said acceptor or one of the necessary intermediates in the biosynthetic pathway of the oligosaccharide of at least four monosaccharide units, advantageously an HMO, particularly an HMO of only four monosaccharide units, from said acceptor.

Abstract: The invention provides a process for synthesizing genes and other long double stranded polynucleotides by assembling very short oligonucleotides into partly double stranded polynucleotides, and then connecting these partly double stranded polynucleotide subassemblies with linkers comprised of very short oligonucleotides. In one embodiment, the correct order of the polynucleotide subassemblies is coded in overhangs present at each end of the partly double stranded polynucleotide subassemblies. Linkers having a sequence complimentary to the combined overhangs connect adjacent subassemblies, which are then ligated together. In one preferred embodiment the oligos are six bases long, for which there are only 4096 different possible sequence permutations. A complete library of oligos of this size and scale can be cost-effectively synthesized and quality controlled, avoiding the typical errors and yield issues associated with phosphoramidite synthesis of longer oligos.

Abstract: The present invention provides a method for self-replication of multimers of nucleic acid origami tiles by exponentially amplifying the multimer from initial seeds of monomeric units of nucleic acid origami tiles and also provides for the selective exponential amplification of a designated multimer, such as with specific properties or characteristics, over one or more competing multimers in the presence of a mixture of monomers for each of the possible multimers. The selection of the designated multimer based on an environmental change allows the designated multimer to outgrow all competing multimers.

Abstract: Disclosed are devices and methods to synthesize polynucleotides and libraries of polynucleotides such as libraries of oligonucleotides. In exemplary embodiments, the device includes a support having a plurality of features. Each feature contains a plurality of oligonucleotides. Within each feature, each of the plurality of oligonucleotides includes an identical predetermined subunit sequence of X nucleosides and a degenerate sequence of Y nucleosides. A predetermined combination of a subset of the features can be used to produce a polynucleotide having a predetermined sequence of Z nucleosides.

Abstract: The present invention provides for an improved process to obtain substantial amount of monoclonal antibodies with desired profile of charged variants. The process involves initially culturing e mammalian cells at a suitable temperature and subsequently reducing the temperature and optionally by simultaneous addition of suitable amino acid(s) during production of the desired molecule. The present invention provides also provides for an antibody having desired profile of glycans prepared with said with improved process.

Abstract: This invention discloses a reagent composition for a biosensor having high sensitivity which is capable of improving analysis linearity of an analyte such as glucose by reacting an oxidoreductase, a metal-containing complex, and Naphthol Green B, and minimizing blood necessary for measuring blood glucose since it is possible to detect a concentration of a small amount of the analyte, and a biosensor having the same. The reagent composition for a biosensor includes at least two kinds of electron transfer mediators including Naphthol Green B, and an enzyme.

Abstract: Disclosed are genes that, when overexpressed in cells expressing alpha-synuclein, either suppress or enhance alpha-synuclein mediated cellular toxicity. Compounds that modulate expression of these genes or activity of the encoded proteins can be used to inhibit alpha-synuclein mediated toxicity and used to treat or prevent synucleinopathies such as Parkinson's disease. Also disclosed are methods of identifying inhibitors of alpha-synuclein mediated toxicity.

Abstract: Methods for identifying fungal species by analysis of fungal membrane lipids, such as glycerophospholipids, sphingolipids and sterols, using mass spectrometry ionization patterns are disclosed.

Abstract: The present specification discloses methods of detecting a pathogen of interest, components useful in carrying out these methods, including a pre-enrichment media, and enrichment media and a detection solution and kits thereof.

Abstract: The present disclosure provides for systems, devices, products, and methods for detecting and identifying microbial organisms in a sample as well as testing antimicrobial susceptibility of microbial organisms.

Abstract: The present disclosure describes methods for concentrating microorganisms with concentration agents in a sampling device and the sampling device described herein. More specifically, methods for concentrating microorganisms from large volume samples with concentration agents in a sampling device can provide for rapid, low cost, simple (involving no complex equipment or procedures), and/or effective processes under a variety of conditions.