Abstract: Embodiments of the present invention concerns methods and compositions for the construction of a series of vectors containing a chemical sensing module to assess the production of a chemical compound by a microorganism.

Abstract: The present invention pertains to the field of diagnostics for neuronal toxicity and toxicological assessments for risk stratification of chemical compounds. Specifically, it relates to a method for diagnosing neuronal toxicity. It also relates to a method for determining whether a compound is capable of inducing such neuronal toxicity in a subject and to a method of identifying a drug for treating neuronal toxicity. Furthermore, the present invention relates to a device and a kit for diagnosing neuronal toxicity.

Abstract: Biomarkers useful for identifying treatments for and monitoring treatment of patients with multiple sclerosis (MS) are provided, as well as methods for their identification, methods of diagnosing MS, relapse of MS patients and disease progression in MS patients.

Abstract: The present invention provides a pharmaceutical composition for preventing or treating angiogenic diseases comprising inhibitors of NUP153 gene expression or NUP153 activity as active ingredient and a method for screening an agent for preventing or treating angiogenic diseases. According to the present invention, inhibition of the NUP153 gene expression or the NUP153 activity reduces export of mRNA of a pro-angiogenic factor (VEGF, HGF and bFGF) from nucleus. In addition, inhibition of the NUP153 gene expression or the NUP153 activity has effect that angiogenesis are inhibited by inhibition of invasion and tube formation in a dose-dependent manner without showing toxicity. Therefore, the pharmaceutical composition of the present invention may be used for preventing or treating a variety of angiogenesis-related diseases, and the method for screening of the present invention may be valuably used in finding a new agent for preventing or treating angiogenic diseases.

Abstract: Methods for treatment and diagnosis of pervasive developmental disorders in humans are described.

Abstract: Provided herein is a three-dimensional scaffold composition comprising randomly oriented fibers, wherein the fibers comprise a polyethylene glycol-polylactic acid block copolymer (PEG-PLA) and a poly(lactic-co-glycolic acid) (PLGA). Also provided are methods for using the three-dimensional scaffolds described herein.

Abstract: A method of qualifying a mesenchymal stem cell (MSC) population is disclosed. The method comprises: (a) ex vivo differentiating a population of mesenchymal stem cells originating from the subject towards a first lineage-specific cell, the first lineage-specific cell being associated with a brain disease; (b) ex vivo differentiating a population of mesenchymal stem cells originating from a healthy subject towards the first lineage-specific cell; (c) comparing an effect of the first lineage specific cell derived from the subject with an effect of the first lineage specific cell derived from the healthy subject on a second lineage specific cell associated with the brain disease, wherein a difference in the effect above or below a predetermined level is indicative of a qualification of a mesenchymal stem cell population for cell therapy of said brain disease.

Abstract: Positive allosteric modulators of melanocortin receptors, especially allosteric potentiators of the receptors MC3R and MC4R are described herein. Also provided are pharmaceutical compositions containing the positive allosteric modulators and methods of treating obesity or an obesity-related disorder such as type 2 diabetes, comprising administering an effective amount of the positive allosteric modulator.

Abstract: The invention provides methods and compositions for the diagnosis, prognosis and treatment of respiratory tract diseases. Specifically, the invention provides diagnosis, prognosis and treatment of respiratory infections using bitter and sweet taste signal transduction pathways. In one aspect, the invention relates to a method for treating a respiratory infection by administering a composition to the respiratory tract of a subject in an amount capable of activating bitter taste signaling and/or inhibiting sweet taste signaling. The composition comprises at least a bitter receptor agonist and, optionally, a pharmaceutically acceptable carrier for delivering the composition to the respiratory tract. In another aspect, the invention relates to a composition for treatment of a respiratory infection. Such composition comprises at least a bitter receptor agonist and, optionally, a pharmaceutically acceptable carrier for delivering the composition to the respiratory tract.

Abstract: The present invention provides methods for obtaining specific and non-toxic inhibitors of AID nuclear import. The methods comprise a primary screen and a counter screen to identify a pool of AID specific nuclear import inhibitors that do not have off-target of toxic effects. AID specific nuclear import inhibitors identified by the screens of the invention prevent nuclear entry, limit the access of AID to genomic DNA, and inhibit AID mutagenic activity. Preparations, including pharmaceutical preparations, comprising specific nuclear import inhibitors, used for example, to inhibit cancer progression, are also encompassed in the invention.

Abstract: Methods for screening libraries of polypeptides for biologically activity on cells. For example, polypeptides can be synthesized and encapsulated along with their coding sequences in microcapsules of an emulsion. Emulsion microcapsules can then be fused with microcapsules comprising test cells and biological activity on the cells is assessed to identify biologically active polypeptides and nucleic acid molecules encoding the same.

Abstract: Theranostics platforms for identifying drugs and nutraceuticals for treatment of rare disease are described. The platforms comprise (a) a cell-phenotype image-enhancing instrument; (b) a drug/nutraceutical library; and (c) a computer-implemented system for analyzing a response of an optically-visible rare-disease cell phenotype to a drug or nutraceutical from the drug/nutraceutical library.

Abstract: The present invention discloses a set of human microRNAs, or a primary transcript for such microRNAs, or a precursor of such microRNAs, or a mimic of such microRNAs or a combination thereof, and their use as medicaments for inducing proliferation of cardiomyocytes for the prevention and treatment of heart diseases associated with a loss of cardiomyocytes. The invention also relates to a method for screening microRNAs and biological and therapeutically active compounds for their ability to increase proliferation of cardiomyocytes.

Abstract: An isolated human brown adipose tissue stem cell line. In one embodiment, the isolated human brown adipose tissue stem cell line expresses the markers CD9, SSEA4, CD44, CD90, CD166, CD73, but not CD14, CD34, CD45 or STRO-1. In another embodiment, the isolated human brown adipose tissue stem cell line expresses the genes UCP1, PPARGC1A, NRF1, FOXC2, CREB1, SIRT3, and WNT5A (REFX). In still another embodiment, the isolated human brown adipose tissue stem cell line is capable of differentiating into osteoblasts, chondrocytes, and adipocytes.

Abstract: The present invention describes a unique antiviral screen system. The assay is based on quantitatively monitoring viral activation of host cell beta-interferon (IFN-?) gene expression in a HEK293-derived reporter cell line expressing a firefly luciferase gene under the control of a human IFN-? promoter. Unlike the traditional high throughput antiviral assays that measure either the reduction of viral components/yields or cytopathic effect, the readout of the reporter assay in the present invention is the virus-induced host cellular innate immune response. Hence, the assay allows for identification of compounds that inhibit virus infection. In addition, because induction of IFN is one of the most common attributes of viruses, the assay is applicable to all the viruses that are able to infect the reporter cell line and induce IFN-? expression.

Abstract: The invention relates to an assay for diagnosing a disease or affliction that affects fluid uptake or secretion or for studying the effectiveness of one or more drugs for treating the disease or affliction, wherein the assay comprises measuring swelling of one or more organoids.

Abstract: The invention refers to a library of bidirectional expression cassettes or expression vectors comprising a repertoire of bidirectional promoter sequences, each expression cassette comprising a promoter sequence operably linked to a first gene in one direction, and operably linked to an oppositely oriented second gene in the other direction which is different from the first gene, and bidirectional Pichia pastoris or CHO cells promoter sequences. The invention further refers to a method of screening or selecting a bidirectional promoter suitable for expressing at least two GOI in a host cell and a kit comprising a) an expression cassette consisting of the first and second genes and a stuffer sequence separating them, which stuffer sequence comprises a recognition site for a type IIS restriction enzyme at both ends; b) the type IIS restriction enzyme; c) and a repertoire of promoter, preferably a promoter library including bidirectional promoters.

Abstract: A target substance used for combination treatment with an anti-c-Met antibody, a pharmaceutical composition for combination administration for preventing and/or treating cancer including an anti-c-Met antibody and an inhibitor against the target substance as active ingredients, a method for preventing and/or treating cancer including co-administering an anti-c-Met antibody and an inhibitor against the target substance, and a method for screening a drug for preventing and/or treating cancer using the target substance.

Abstract: The present invention refers to a method for controlling undesired vegetation at a plant cultivation site, the method comprising the steps of providing, at said site, a plant that comprises at least one nucleic acid comprising a nucleotide sequence encoding a wild-type hydroxyphenyl pyruvate dioxygenase or a mutated hydroxyphenyl pyruvate dioxygenase (mut-HPPD) which is resistant or tolerant to a coumarone-derivative herbicide and/or a nucleotide sequence encoding a wild-type homogentisate solanesyl transferase or a mutated homogentisate solanesyl transferase (mut-HST) which is resistant or tolerant to a coumarone-derivative herbicide, and applying to said site an effective amount of said herbicide. The invention further refers to plants comprising mut-HPPD, and methods of obtaining such plants.

Abstract: Disclosed herein are compositions and methods to treat and reduce therapeutic resistance in chronic myelogenous leukemia. Also disclosed herein are methods to generate leukemia stem cell like cells (iLSCs) generated from CML patient-derived iPSCs, and methods for utilizing iLSCs in screens to identify modulators of CML drug resistance and gene targets that underlie CML drug resistance.

Abstract: The invention provides compounds, compositions, methods, substrates, and kits useful for analyzing the metabolic activity in cells, tissue, and animals and for screening test compounds for their effect on cytochrome P450 activity. In particular, a one-step and two-step methods using luminogenic molecules, e.g. luciferins or coelenterazines, that are cytochrome P450 substrates and that are also bioluminescent enzyme, e.g., luciferase, pro-substrates are provided. The present method further provides a method for stabilizing and prolonging the luminescent signal in a luciferase-based assay using luciferase stabilizing agents such as reversible luciferase inhibitors.

Abstract: Stable, constitutively expressed, chromosomal fluorescent transcriptional fusions in bacterial pathogens and methods of using the same to screen candidate compounds for anti-bacterial efficacy.

Abstract: Fluorescent dyes useful for preparing fluorescent metal ion indicators, the fluorescent indicators themselves, and the use of the fluorescent indicators for the detection, discrimination and quantification of metal cations are provided.

Abstract: This invention provides compounds capable of reducing drug resistance in a subject undergoing cancer treatment, methods using the compounds, compositions, and methods for identifying such compounds.

Abstract: Methods are provided for producing novel multicellular compositions comprising cancer cells together with pluripotent human stem cells, which are capable of proliferating and differentiating into various normal cell lines and tissue structures. These novel multicellular compositions are useful for investigating the properties of cancer cells in a normal human tissue microenvironment, and for studying interventions that will modulate these properties including devising, testing and screening therapeutic drugs.

Abstract: This invention relates to the use sigma-2 receptor antagonists, and of pharmaceutical compositions comprising such compounds, in methods for inhibiting Abeta-associated synapse loss or synaptic dysfunction in neuronal cells, modulating an Abeta-associated membrane trafficking change in neuronal cells, and treating cognitive decline associated with Abeta pathology and more broadly treating with such compounds and compositions neurodegenerative diseases and disorders associated with Abeta pathology. This invention also relates to methods for screening compounds for activity in inhibiting cognitive decline on the basis of their ability to bind to a sigma-2 receptor.

Abstract: A bacillus composition characterized by fast germination and outgrowth in bile salts (simulated gut environment) and by producing a compound of interest. The bacillus composition may be used as supplement in animal feed where it has a probiotic (health promoting) effect and increases the digestion and availability of nutrients from animal feeds.

Abstract: An aspect of the invention provides a method of selectively necrosing cells, comprising: providing a plurality cells, including at least one cancer cell and at least one non-cancerous cell; and administering to the cells a compound, including an HDM-2 targeting component and a cytotoxic component attached to the HDM-2 targeting component, wherein said compound comprises a membrane-active form.

Abstract: Aspects of the present invention relate to the determination of the DNA methylation level at one or more CpG position within cells of a defined type in a tissue sample. This methylation level is deduced from the total DNA methylation level of all cells of the sample and from the content of said cells of interest. In aspects of the invention, the cell content is determined by means of histopatholoy, staining methods, antibodies, expression analysis or DNA methylation analysis.

Abstract: The present invention provides, inter alia, a method for identifying an agent that selectively decreases the number of cancer stem cells (CSCs). This method includes (a) contacting a CSC from a population of cells with a candidate agent; and (b) determining whether the candidate agent reduces the survival or growth of the CSC or increases differentiation of the CSC relative to a CSC that has not been contacted with the candidate agent. The method may be used as a high throughput screen.

Abstract: This invention provides transcription regulatory control sequences, the activity of which function as biomarkers for a variety of biological responses. This invention also provides expression constructs in which a biomarker transcription regulatory sequence is operably linked with a sequence for a reporter. Cells that comprise these expression constructs can be used in assays to identify conditions that modulate activity of the biological response.

Abstract: The present disclosure relates general to devices, systems, and methods of using such devices in creating and handling hanging drops of fluid. The present disclosure also relates to cell culture devices, methods and/or systems of using such devices as well as the use of cell culture devices, for example, for research and high throughput screening.

Abstract: The present invention provides screening methods which may be regarded as in vitro or ex vivo methods of interrogating the immune system to understand what viral antigens are “seen” and responded to by T cells of the immune systems during viral infection. The screening methods further link in vitro or ex vivo responses to progression of infection in subjects.

Abstract: A system and method for isolating cells, comprising: a substrate having a broad surface; an array comprising a set of wells defined at the broad surface of the substrate, each well including: a base surface, an open surface directly opposing the base surface, defined at the broad surface of the substrate, and configured to receive one of a single cell and a single cluster of cells from a direction perpendicular to the broad surface of the substrate, and a set of channels that fluidly couple each well to at least one adjacent well; wherein the set of wells includes an interior subset and an exterior subset fluidly coupled to and surrounding the interior subset by way of the set of channels; and a fluid delivery module surrounding the array and fluidly coupled to each well in the set of wells.

Abstract: Compositions, methods, and kits are provided for reduction of (CAG)n-RNA mediated toxicity. Compositions, methods, and kits are also provided for treatment of polyglutamine diseases.

Abstract: The present invention refers to a method for controlling undesired vegetation at a plant cultivation site, the method comprising the steps of providing, at said site, a plant that comprises at least one nucleic acid comprising a nucleotide sequence encoding a wild-type hydroxyphenyl pyruvate dioxygenase or a mutated hydroxyphenyl pyruvate dioxygenase (mut-HPPD) which is resistant or tolerant to a coumarone-derivative herbicide and/or a nucleotide sequence encoding a wild-type homogentisate solanesyl transferase or a mutated homogentisate solanesyl transferase (mut-HST) which is resistant or tolerant to a coumarone-derivative herbicide, and applying to said site an effective amount of said herbicide. The invention further refers to plants comprising mut-HPPD, and methods of obtaining such plants.

Abstract: A method for forming neuromuscular junctions includes forming functional neuromuscular junctions between motoneurons and muscle cells by co-culturing one or more human motoneurons and one or more human muscle cells in a substantially serum-free medium. A synthetic mammalian neuromuscular junction includes a human motoneuron functionally linked to a human muscle cell in a substantially serum-free medium. An artificial substrate may be used to support the one or more neuromuscular junctions.

Abstract: The invention provides a method for producing an orexin neuron by culturing a pluripotent stem cell or a neural progenitor cell in the presence of N-acetyl-D-mannosamine and optionally in the presence of at least one inhibitor selected from the group consisting of a Sirtuin 1 inhibitor and an O-linked ?-N-acetylglucosamine transferase inhibitor. The invention also provides a therapeutic agent for narcolepsy or eating disorders, such as anorexia, containing N-acetyl-D-mannosamine, which is based on the induction of orexin neuron in vivo.

Abstract: The present invention relates to a method of identifying candidate compounds useful as chemotherapeutics or anti-infective compounds or anti-inflammatory drugs. This method involves providing a plurality of test compounds. The plurality of test compounds are incubated with human Regulatory T (Treg) cells expressing Disc-Large Homo log 1 (Dlgh1) or in which Dlgh1 is suppressed, where the Treg cells have an immunological synapse (IS). Test compounds which inhibit Dlgh1 expression, recruitment to the IS, and/or activity in the Treg cells are identified as candidate compounds potentially useful as chemotherapeutics or anti-infective compounds. Test compounds which enhance Dlgh1 recruitment to the IS and/or activity in the Treg cells are identified as candidate compounds potentially useful as anti-inflammatory drugs. The present invention also relates to methods of treating inflammatory conditions, cancers, and infectious diseases in a subject, as well as methods of inhibiting Treg cell activity.

Abstract: The present invention provides methods for identifying cognitive enhancers able to enhance CREB pathway function. Cognitive enhancers identified in accordance with the invention can be used in rehabilitating an animal with cognitive dysfunction and for enhancing memory or normal cognitive performance (ability or function) in the animal.

Abstract: Novel methods for modulating acute myeloid leukemia stem/progenitor cell expansion and/or differentiation are disclosed. These methods are based on the use of aryl hydrocarbon receptor (AhR) modulators and/or compounds of formula I or II Screening assays to identify compounds that may be useful for inhibiting and/or eliminating AML initiating cells using AhR modulators and/or the compounds of formula I or II are also disclosed. The use of pharmaceutically acceptable agonists of the AhR for preventing or inhibiting minimal residual disease (MRD) in an AML patient is also disclosed.

Abstract: The present invention relates to the generation of stable haploid cell cultures, uses of said cells in forward and reverse genetics, especially the identification of target genes associated with a modified phenotype and in particular identifying genetic targets associated with toxin resistance, especially ricin toxicity resistance, and therapeutic uses of target compounds.

Abstract: A kit and method for evaluating in vitro the effect of a xenobiotic (e.g., a biologic drug) on drug metabolism in hepatocytes. The kit comprises a first culture of hepatocytes, a portion of in vitro xenobiotic-stimulated biological sample, and instructions for incubating the first culture of hepatocytes with the portion of in vitro xenobiotic-stimulated biological sample, and analyzing the activity, expression, or a combination thereof of a biomarker in the hepatocytes to evaluate the effect of the xenobiotic on drug metabolism in the hepatocytes.

Abstract: The present invention relates to methods of inhibiting seizure in a subject. In particular, the invention provides methods of increasing brain leptin levels in a subject.

Abstract: This disclosure provides a novel role for microRNA (miR) regulation of lipid metabolism via the MTP pathway, leading to reductions in apoB secretion and blood lipid levels. MiR regulation of the MTP pathway is shown herein to reduce hyperlipidemia and atherosclerosis in vivo. Therefore, inhibition of MTP expression and activity by miR regulation is identified as a new therapeutic target for treatment of cardiovascular disease and conditions or diseases associated with cardiovascular disease such as hyperlipidemia, atherosclerosis, and metabolic syndrome. Treatment of cardiovascular disease and associated conditions or diseases with the novel MTP inhibitors of the invention, such as miR-30c homologs or miR-30c agonists, reduces MTP-associated lipid production without side effects that occur with other methods of MTP inhibition.

Abstract: Provided is a method of treating or preventing age-related macular degeneration (AMD) in a patient subject to, or symptomatic of the disease, wherein the method comprises restoring normal lysosomal pH (pHL), or acidifying an abnormally elevated pHL, thus decreasing or preventing a damaging accumulation of lipofuscin or waste products in the retinal pigment epithelium (RPE) cells of the eye of the patient. Further, this method is achieved by modulating the action of the P2X7 and/or P2Y12 receptors of the RPE cells, specifically decreasing the acidity (pHL) of the RPE lysosomes by administering selected receptor antagonists affecting the action of the P2X7 and/or P2Y12 receptors of the RPE. Methods for selecting and quantifying the effectiveness of drugs to restore pHL and determine outer segment clearance rates is also provided using a high through-put screening protocol.

Abstract: This invention discloses devices and methods for high throughput skin sensitization detection. The devices comprise a microfabricated chamber comprising a region having one or more input channels and an outlet, and a face suitable for mounting a skin tissue and in fluidic communication with the region. The devices can be used in the methods for determining a prognosis of sensitization in an animal subject and identifying compounds that do not cause sensitization and thus are suitable for preparing cosmetic compositions.

Abstract: Compositions and methods for treatment of Sturge-Weber Syndrome, Klippel-Trenaunay-Weber Syndrome, Port-Wine Stains and related neurocutaneous disorders are provided. Cell lines having the somatic mutation GNAQ p.Arg183Gln amino acid substitution, which was found to be the cause of port-wine stains (prevalence 1 in 300) and Sturge-Weber syndrome are also provided. Compositions and methods for treatment of uveal melanoma are also provided herein. Methods of screening novel compounds and compositions useful in increasing RGS2 and/or RGS4 expression and function in vitro, and for treatment of Sturge-Weber Syndrome, Klippel-Trenaunay-Weber Syndrome, Port-Wine Stains and related neurocutaneous disorders are provided are also provided.

Abstract: Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.

Abstract: A method of predicting cell toxicity of a compound includes imaging cells positioned within a plurality of containers to obtain imaged cellular targets, each container being treated with a different concentration of the compound, the imaging being performed using a quantitative high-content cell imaging system; quantitatively measuring the imaged cellular targets to detect changes in multiple cellular targets associated with cytotoxicity of the compound; and analyzing measurements obtained from the measured imaged cellular targets over a range of compound concentrations to determine the toxicity of the compound.