Abstract: The invention relates to methods and assays for the detection of active Alternative Lengthening of Telomeres (ALT) activity in cells. The methods and assays involve detecting or assaying for partially double-stranded telomeric circles wherein the presence of said circles is specific for cells comprising an active ALT mechanism. In some embodiments the methods find application in, inter alia, determining the level of ALT activity in a cell, determining the ALT status of a cancer in a subject, diagnosing and/or treating disease, determining disease status, analysis of treatment efficacy, and the identification of novel therapeutic agents.

Abstract: The invention describes methods that are useful for treating cancer by administering a Chk1 inhibitor which can induce apoptosis in p53-defective cells when combined with a chemotherapy and/or radiotherapy. Methods for screening candidates for a Chk1 inhibitor-based cancer treatment regimen are also described.

Abstract: The present invention relates to a corn plant and seed with enhanced levels of protein and amino acids. The invention also relates to DNA constructs that provide expression in transgenic corn cells of an asparagine synthetase enzyme. The DNA constructs are used in a method to produce transgenic corn plants and seeds and to select for plants and seeds with enhanced levels of protein and amino acids.

Abstract: The present invention relates to agonists of Neprilysin and their use in preventing and treating pulmonary vascular remodeling. Also described are diagnostic and screening applications stemming from the inventor's discovery that Neprilysin is expressed at reduced levels in disease tissues.

Abstract: The present invention is based, in part, on our studies of molecular pathways that include the deubiquitinase CYLD. Accordingly, the present invention features, inter alia, nucleic acid constructs that express CYLD or a biologically active variant thereof (e.g., a variant including the catalytic domain), nucleic acids that inhibit the expression of a negative regulator of CYLD (e.g., PDE4B or LNK2), nucleic acids that modulate the expression of downstream CYLD targets (e.g., Akt, by inhibiting or promoting the expression of the downstream target), compositions including one or more of these types of constructs (e.g., pharmaceutical compositions), kits including one or more of the compositions described herein and instructions for use, screening methods to identify therapeutic agents {e.g., anti-inflammatory agents) that upregulate CYLD, downregulate a negative regulatory of CYLD, or modulate (e.g., inhibit) a downstream CYLD target (e.g.

Abstract: Compositions and methods are provided for genome modification of a target sequence in the genome of a cell. The methods and compositions employ a guide polynucleotide/Cas endonuclease system to provide an effective system for modifying or altering target sites within the genome of a cell or organism. Once a genomic target site is identified, a variety of methods can be employed to further modify the target sites such that they contain a variety of polynucleotides of interest. Compositions and methods are also provided for editing a nucleotide sequence in the genome of a cell. Breeding methods and methods for selecting plants utilizing a two component RNA polynucleotide and Cas endonuclease system are also disclosed.

Abstract: The present invention relates to a kit for detection of association of a peripheral cellular membrane binding protein with cellular membranes in living cells and methods thereof. The kit includes a first nucleic acid construct comprising a first nucleic acid molecule encoding a first fusion protein comprising a peripheral cellular membrane binding protein or membrane binding domain thereof operatively coupled to DNA binding and transactivation domains of a naturally occurring or chimeric transcription factor and a first promoter operatively associated with the first nucleic acid molecule. A second nucleic acid construct comprises a second nucleic acid molecule encoding a reporter protein and a second promoter responsive to the DNA binding and transactivation domains of the first fusion protein. The second promoter is operatively associated with the second nucleic acid molecule. Activation of the second promoter results in expression of the reporter protein. Also disclosed is a transgenic non-human animal.

Abstract: This invention relates to a composition, kit, or DNA chip for use in diagnosis of esophageal cancer, which comprises a plurality of polynucleotides selected from the group consisting of polynucleotides whose expression levels are varied in esophageal cancer tissues obtained from esophageal cancer patients when compared with cancer-free esophageal tissues obtained from esophageal cancer patients, mutants thereof, and fragments thereof, and to a method for detecting esophageal cancer using the composition, kit, or DNA chip.

Abstract: The present invention improves in vitro virus synthesis efficiency and stability of mRNA derived from screened cDNA in a cDNA display method to improve the efficiency and reliability of the production of a peptide by a molecular evolutionary engineering technique. Provided is a ligand which comprises three fingers formed from antiparallel ?-sheets and a loop region intercalated between the antiparallel ?-sheets, wherein at least a fingertip part formed by the loop region of each of the fingers is bound to the target molecule, and wherein the ligand comprises the amino acid sequence of SEQ ID NO: 1. In the amino acid sequence of SEQ ID NO: 1, X7 represents an arbitrary amino acid residue that constitutes the fingertip part of each of the fingers, each numeric character represents the number of amino acid residues, and X7 and X4 are not composed of the same amino acid residues as each other.

Abstract: A multidimensional profiling strategy that combines activity-based proteomics and metabolomics was used to determine that an active protein, which is a previously uncharacterized enzyme highly elevated in aggressive cancer cells, serves as a central node in an ether lipid signaling network that bridges platelet-activating factor and the lysophospholipids. Biochemical studies confirmed that the active protein regulates this pathway by hydrolyzing the metabolic intermediate 2-acetyl monoalkylglycerol. Inactivation of the active protein disrupted ether lipid metabolism in cancer cells and impaired cell migration and tumor growth in vivo.

Abstract: Diagnostic and therapeutic applications for Noonan Syndrome are described. The diagnostic and therapeutic applications are based on certain mutations in a RAS-specific guanine nucleotide exchange factor gene SOS1 or its expression product. The diagnostic and therapeutic applications are also based on certain mutations in a serine/threonine protein kinase gene RAFl or its expression product thereof. Also described are nucleotide sequences, amino acid sequences, probes, and primers related to RAF1 or SOS1, and variants thereof, as well as host cells expressing such variants.

Abstract: Methods of modifying, repairing, attenuating and inactivating a gene or other chromosomal DNA in a cell are disclosed. Also disclosed are methods of treating or prophylaxis of a genetic disease in an individual in need thereof. Further disclosed are chimeric restriction endonucleases.

Abstract: The present invention provides a method for screening and evaluating ameliorants of dry skin caused by atopic dermatitis, comprising: evaluating a candidate drug as being an ameliorant of dry skin caused by atopic dermatitis in the case the candidate drug significantly increases expression and/or activity of bleomycin hydrolase in comparison with a control drug.

Abstract: The invention relates to inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono- through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.

Abstract: The present invention relates to agonists of Neprilysin and their use in preventing and treating pulmonary vascular remodeling. Also described are diagnostic and screening applications stemming from the inventor's discovery that Neprilysin is expressed at reduced levels in disease tissues.

Abstract: The present invention relates to targeting an intracellular enzyme for release of covalently linked bioactives which results in a synergistic effect between the bioactives. The present invention relates to the use of bioactives that are directly connected covalently or through a covalent molecular linker which have increased therapeutic activity when released as the free bioactives by intracellular enzymes as compared to when the bioactives are administered individually (i.e. not covalently linked). Further, methods are described of administering to patients in need thereof, bioactives as linked bioactives having increased therapeutic activity. Accordingly, this invention also relates to methods of treating patients for certain diseases.

Abstract: The present invention provides a method of making biological containment factors for use in selectively killing target bacteria such as Bacillus anthracis, Clostridium botulinum, Clostridium perfringens, and other select agents.

Abstract: The object is to provide: a therapeutic or prophylactic agent for metabolic syndrome, which has improved stability in a living body; and others. The therapeutic or prophylactic agent for metabolic syndrome comprises, as an active ingredient, DNA that encodes receptor activity-modifying protein (RAMP) 2 and is selected from the items (a) to (d) below or a polypeptide encoded by the DNA: (a) DNA which has the nucleotide sequence depicted in SEQ ID NO:1; (b) DNA which has a nucleotide sequence capable of hybridizing with the nucleotide sequence depicted in SEQ ID NO:1 under stringent conditions; (c) DNA which has a nucleotide sequence encoding an amino acid sequence having the substitution, deletion and/or addition of one or more amino acid residues in the amino acid sequence depicted in SEQ ID NO:2; and (d) DNA which has a nucleotide sequence having a 90% or more homology with the nucleotide sequence depicted in SEQ ID NO:1.

Abstract: The present invention is directed to alpha-mannosidase sequences from plants and the use thereof, especially genomic nucleotide sequences containing the regulatory elements controlling their expression, intron and exon sequences and polynucleotide sequences coding for alpha-mannosidase enzymes. Such plants with modified alpha-mannosidase activity can be used for the production of glycoproteins having an altered saccharide composition of great benefit. The present invention also relates to the use of these alpha-mannosidase enzymes for hydrolyzing mannoses.

Abstract: Methods for identifying a therapeutic agent for treating a Germinal Center Kinase (GCK)-Like Kinase (GLK)-mediated disease are disclosed. Methods for detecting a modulation of GLK signaling by a test compound are disclosed. Also disclosed are methods for detecting the presence and/or severity of an autoimmune disease and/or cancer.

Abstract: Provided are compositions and methods for labeling an endogenous protein, in particular, in a live cell, or for ablating an endogenous or target protein. The compositions relate to a fusion protein having a binding moiety such as an antibody, an antigen binding fragment of an antibody or an antibody mimetic that recognizes the endogenous or target protein.

Abstract: A method of treating cancer is disclosed. The method comprises administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an agent which induces a dissociation of the 26S proteasomal complex into a 20S component and a 19S component to thereby inhibit 26S proteasomal activity, wherein the pharmaceutical agent is devoid of a chemotherapeutic agent.

Abstract: It is discovered that noscapine is effective in treating temozolomide (TMZ)-resistant brain cancer. Provided are compositions and methods of treating brain cancer patients, in particular those that are TMZ-resistant. The patients are treated by administration of a therapeutically effective amount of noscapine or an analog thereof. In certain aspects, TMZ is also administered to the patients. Examples of brain cancers include glioma such as glioblastoma multiforme.

Abstract: The present invention relates to a noninvasive method for quantifying Fel d 1 cat allergen expression levels—the major allergen responsible for cat allergies—in individual cats (Felis catus).

Abstract: The electrical properties of particle solutions can be investigated on a single particle basis by using micro fluidic channels. The impedance can be measured across the channel using at least one pair of conductive electrodes, at least one electrode of a pair being a fingered electrode having a plurality of fingers. The pattern of fingered electrodes creates a longer and more complicated measurement signal shape which leads to a significant improvement of measurement sensitivity. An application for the proposed technology is to significantly improve the measurement sensitivity of impedance measurements on blood cells, leading to a better differentiation between different types of white blood cells. Better measurement sensitivity also enables the measurement of smaller particles and higher throughput.

Abstract: Compositions and methods reduce the expression of endogenous ACC oxidase genes to improve an agronomic characteristic of a crop plant, which may be maize. Yield increase and drought tolerance due to reduction in the endogenous ACC oxidase levels are observed. ACC oxidase genes are identified in maize, rice, and Arabidopsis genomes.

Abstract: The invention described herein features methods, compositions, and kits that utilize activators of pyruvate kinase M2 (PKM2) for the treatment or amelioration of disorders related to PKM2 function and characterized by abnormally low levels of serine.

Abstract: Compositions and methods useful in determining the major morphological types of lung cancer are provided. The methods include detecting expression of at least one gene or biomarker in a sample. The expression of the gene or biomarker is indicative of the lung tumor subtype. The compositions include subsets of genes that are monitored for gene expression. The gene expression is capable of distinguishing between normal lung parenchyma and the major morphological types of lung cancer. The gene expression and somatic mutation data are useful in developing a complete classification of lung cancer that is prognostic and predictive for therapeutic response. The methods are suited for analysis of paraffin-embedded tissues. Methods of the invention include means for monitoring gene or biomarker expression including PCR and antibody-based detection. The biomarkers of the invention are genes and/or proteins that are selectively expressed at a high or low level in certain tumor subtypes.

Abstract: A radioluminescence microscopy system and method for imaging the distribution of radiolabeled molecules in live cell cultures and tissue sections. Cells are grown and incubated with radiolabeled molecules on a scintillator plate or a scintillator plate is placed adjacent to the cells after incubation. Scintillation light produced by decay of radiolabeled molecules inside, bound to, or surrounding the cells, is recorded on an imaging device. Fluorescence microscopy of the same cells with other types of molecules of interest that are labeled with different fluorophores can be conducted concurrently and the biological activity of the labeled molecules can be correlated.

Abstract: Methods for treating cardiovascular disease, and in particular heart failure, are provided comprising administering a therapeutically effective amount of a modulator of SERCA2a post-translation modification such as SUMOylation or acetylation. Also provided are methods of treating cardiovascular disease by inhibiting SERCA2a degradation. Further provided are methods of diagnosing a propensity to develop heart failure comprising determining if a SERCA2a mutant is present or determining the level of expression of SUMO1 in cardiomyocytes. The disclosure also provides methods of screening for therapeutics that modulate the post-translational modification of SERCA2a, such as by modulating post-translational SUMOylation and/or acetylation.

Abstract: The present invention relates to expression vector comprising (a) a promoter region comprising a non-inducible constitutively active ribosomal protein gene promoter, (b) an operably linked reporter or gene sequence, and (c) a 3? untranslated region (3? UTR), which are suitable means for an selective assessment of post-transcriptional regulation, post-transcriptional control elements and factors as well as for identifying compounds that effect post-transcription. The present invention furthermore relates to arrays, expression vector libraries and cell lines containing the expression vector(s). The present invention furthermore relates to a method and kit for identifying compounds that affect post-transcriptional regulation of reporter(s) or gene(s), that utilize the expression vector(s).

Abstract: The present invention provides duplexed parvovirus vector genomes that are capable under appropriate conditions of forming a double-stranded molecule by intrastrand base-pairing. Also provided are duplexed parvovirus particles comprising the vector genome. Further disclosed are templates and methods for producing the duplexed vector genomes and duplexed parvovirus particles of the invention. Methods of administering these reagents to a cell or subject are also described. Preferably, the parvovirus capsid is an AAV capsid. It is further preferred that the vector genome comprises AAV terminal repeat sequences.

Abstract: Disclosed are methods of identifying a genetic variant in a person determined to have or be predisposed having a fatty liver by determining whether the person has PNPLA3-I148M. Also disclosed are methods of identifying a genetic variant in a person by determining whether the person has PNPLA3-I148M; and prescribing to the person a treatment to reduce liver fat or associated inflammation.

Abstract: The present invention relates to immunostimulatory oligodeoxynucleotides, vectors and vaccines comprising such oligodeoxynucleotides, to their use as a medicament, to their use in preventing or combating infectious disease, to methods for the detection of such oligodeoxynucleotides and to cells to be used in these methods.

Abstract: Methods and compositions for providing a prognosis or diagnosis for a human patient having renal cell cancer are provided. The method relates to the discovery of SNPs which are associated with a favorable prognosis and response to therapy in RCC.

Abstract: The present invention provides compositions and methods for detection and analysis of intracellular binding of a bioactive agent to a cellular target. In particular, provided herein are bioactive agents tethered to fluorophores, cellular targets fused to bioluminescent reporters, and methods of detecting and analyzing the interaction of bioactive agents with cellular targets therewith.

Abstract: Methods and means are provided to modify in a targeted manner the genome of a plant in close proximity to an existing elite event using a double stranded DNA break inducing enzyme. Also provided are plants, in particular cotton plants showing tolerance to a field dose of at least 1× of at least one HPPD inhibitor, and methods for making such plants.

Abstract: Methods for making transgenic plants that are resistant to HPPD herbicides are presented. Polynucleotides other than those from Pseudomonas fluorescens that encode resistant HPPD enzymes are enclosed for use in the process of making transgenic plants that are tolerant to HPPD-inhibiting herbicides.

Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.

Abstract: The present invention provides a photobiological ethanol production and harvesting technology using greenhouse distillation systems with designer photosynthetic organisms, such as designer transgenic oxyphotobacteria. The designer oxyphotobacteria are created such that the endogenous photobiological regulation mechanism is tamed, and the reducing power (NADPH) and energy (ATP) acquired from the photosynthetic process are used for synthesis of ethanol (CH3CH2OH) directly from carbon dioxide (CO2) and water (H2O). The designer use of a pair of NADPH-dependent vs. NAD-dependent glyceraldehyde-3-phosphate dehydrogenases in the pathway designs offers a special cyclic “transhydrogenase” redox-shuttle function to convert NADPH to NADH for enhanced photobiological ethanol production. Through combined use of a designer photosynthetic organism with a greenhouse distillation system, the waste solar heat associated with the photobiological ethanol-production process is utilized in harvesting the produced ethanol.

Abstract: Described herein are novel nucleic acids, proteins and methods that can be used to provide new catalysts with desirable traits for industrial processes. In particular, novel reductases isolated from the environment using PCR methods are described.

Abstract: The present invention identifies and quantifies changes in gene expression associated with non-small cell lung cancer NSCLC by examining gene expression in tissue from normal lung and diseased lung. The present invention also identifies and quantifies expression profiles which serve as useful diagnostic markers as well as markers that are useful to monitor disease states, disease progression, drug toxicity, drug efficacy and drug metabolism.

Abstract: Provided herein are methods for preventing or treating bronchopulmonary dysplasia (BPD) in a subject. The methods comprise identifying connective tissue mast cells (CTMCs) in a subject and administering an agent that blocks an activity of blocks an increase in a level of or reduces a level of the CTMCs in the subject. Also provided are methods of identifying a subject with or at risk for developing BPD. Also provided are methods for determining the effectiveness of a treatment regime for BPD in a subject.

Abstract: The invention provides non-naturally occurring microbial organisms having a toluene, benzene, p-toluate, terephthalate, (2-hydroxy-3-methyl-4-oxobutoxy)phosphonate, (2-hydroxy-4-oxobutoxy)phosphonate, benzoate, styrene, 2,4-pentadienoate, 3-butene-1ol or 1,3-butadiene pathway. The invention additionally provides methods of using such organisms to produce toluene, benzene, p-toluate, terephthalate, (2-hydroxy-3-methyl-4-oxobutoxy)phosphonate, (2-hydroxy-4-oxobutoxy)phosphonate, benzoate, styrene, 2,4-pentadienoate, 3-butene-1ol or 1,3-butadiene.

Abstract: Disclosed herein is the identification of human DNA polymerase ? (pol ?) as the polymerase that mediates repair of DNA containing interstrand cros slinks (ICLs). The mechanism of action of a number of chemotherapeutic and antimicrobial agents is the induction of ICLs. Thus, provided herein is a method of enhancing the efficacy of a chemotherapeutic or antimicrobial agent in a subject, including selecting a subject in need of treatment with an ICL -inducing agent and administering to the subject an ICL-inducing agent and a therapeutically effective amount of an inhibitor of pol ?. Also provided is a composition for treating a hyperproliferative disease, an autoimmune disease or an infectious disease, comprising an ICL-inducing agent and an amount of an inhibitor of pol ? sufficient to enhance the efficacy of the ICL-inducing agent. Further provided is a method of identifying a DNA polymerase inhibitor.

Abstract: A polynucleotide encoding a modified luciferase polypeptide. The modified luciferase polypeptide has at least 60% amino acid sequence identity to a wild-type Oplophorus luciferase and includes at least one amino acid substitution at a position corresponding to an amino acid in a wild-type Oplophorus luciferase of SEQ ID NO:1. The modified luciferase polypeptide has at least one of enhanced luminescence, enhanced signal stability, and enhanced protein stability relative to the wild-type Oplophorus luciferase.

Abstract: The invention relates to mTORbeta, a splice form of mTOR, nucleic acids encoding mTOR beta, and antibodies against mTOR beta. The invention also relates to methods of producing mTOR beta and methods of screening for an agent that modulates mTOR beta expression and/or activity. The invention further relates to a method of treating a disease associated with aberrant expression of mTOR beta by administration of an agent that alters mTOR activity and/or expression.

Abstract: A nucleic acid sequence, including an isolated, purified or recombinant nucleic acid sequence, includes: (a) a nucleic acid sequence encoding a polypeptide encompassed by the present invention, namely, a PLC-zeta; PLC? amino acid sequence, capable of triggering calcium oscillations in oocytes; (b) a sequence substantially homologous to or that hybridizes to sequence (a) under stringent conditions; (c) a sequence substantially homologous to or that hybridizes to the sequences (a) or (b) but for degeneracy of the genetic code; and (d) an oligonucleotide specific for any of the sequences (a), (b) or (c) above.

Abstract: The present invention relates to a bi-directional cytosine deaminase-encoding selection marker as well as methods for using said marker.

Abstract: The invention relates to determining the presence of an EZH2 gene mutation in a sample from a subject and inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono-through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.