Abstract: Disclosed herein are cells and cell lines that stably express CFTR and methods for using those cells and cell lines. The invention also includes techniques for creating these cells and cell lines. The cells and cell lines of this invention are physiologically relevant. They are highly sensitive and provide consistent and reliable results in cell-based assays.

Abstract: The present invention concerns a method for identifying inhibitors against dengue virus subtypes 1, 2, 3 or 4 and its use in a high throughput mode.

Abstract: The invention relates to a nucleic acid comprising the following contiguous elements arranged in the 5 prime to 3 prime direction; a promoter; a selectable marker; a cloning site for receipt of a nucleic acid segment, said segment comprising a candidate miRNA target sequence; and a poly adenylation signal, said elements arranged such that a transcript directed by said promoter comprises said selectable marker, said candidate miRNA target sequence, and said poly adenylation signal in that order. Suitably the miRNA test sequence is or is derived from a 3?UTR. The invention also relates to methods for making and screening libraries.

Abstract: Provided is a method and growth chamber for the rapid and accurate detection of growth and metabolism of a cellular microorganism in isolation within one or a plurality of wells containing a population of microorganisms in a non-liquid, culture medium, wherein the cells are distributed at not greater than one cell per well at plating. Further provided is a gelled culture medium containing a non-toxic, water-soluble, phosphorescent compound which measures oxygen content (partial oxygen pressure) of a microorganism also contained therein, by oxygen-dependent quenching of phosphorescence; or the gel contains a fluorescent pH indicator that demonstrates growth of the microorganism by pH-dependent intensity change or wavelength shift in the emission spectrum.

Abstract: The present invention provides, in part, platforms for analyzing an aspect of synaptic vesicle cycling. According to other aspects, the invention provides neuronal cell culture platform and platforms for analyzing an aspect of synaptic vesicle cycling. According to other aspects, the invention provides methods of measuring an aspect of synaptic vesicle cycling in a plurality of cells. According to other aspects, the invention provides methods for identifying a test agent as a modulator of an aspect of synaptic vesicle cycling.

Abstract: The invention provides compounds of general formulae (I)-(IV) or pharmaceutically acceptable salts thereof: The invention also provides methods of preparing the compounds, pharmaceutical compositions comprising the compounds and use of the compounds for the preparation of medicaments intended to modulate the activity of one or more members of the G-protein coupled receptor (GPCR) class. Compounds of the invention may be used to create a compound library for use in screening for agents which modulate signalling through GPCRs.

Abstract: The invention provides methods and compositions for detecting and measuring the amount of autophagosomes in cells or tissues, including biopsy samples, in vitro, in situ and/or in vivo. By detecting and measuring the amount of autophagosomes in cells or tissues, the methods and compositions of the invention also measure the amount of autophagic activity in a cell or a tissue. In one aspect, the invention can be adapted to a plate-reader format for high-throughput screening of drugs that modulate autophagy, i.e., high-throughput detection of autophagic (autophagosome) activity in cells or tissues. In alternative embodiments, the compositions of the invention can localize into autophagosomes (AV), and these compositions can comprise any detectable moiety or group, e.g., a cadaverine, a radioactive, fluorescent-, bioluminescent and/or paramagnetic-conjugated reagent.

Abstract: The present invention relates to a method and kit of detecting a target material using an aptamer, and more particularly to a method and kit for detecting a target material, in which a sample and a second aptamer are added to a first aptamer immobilized on a solid phase so as to form a bond sandwiched between the first aptamer, the target material and the second aptamer, to an FET sensor-based method and kit for detecting a target material, and to an AAO sensor-based method and kit for detecting a target material. The inventive method for a target material using an aptamer can detect even low-molecular-weight materials which were difficult to detect in the prior art, thereby enabling detection of disease-related metabolites, environmental pollutants and food toxins in solutions. In addition, the detection method of the present invention is a direct and simple method and is highly cost-effective, because it uses the aptamer which can be consistently reproduced and can be produced at low costs.

Abstract: This invention provides a novel screening system for identifying p53 mimetics/agonists. Also provided are small organic molecules that act as effective p53 mimetics/agonists.

Abstract: The present invention relates to methods for detecting, prognosing and staging cancers, in particular cancers of the gastrointestinal tract. The methods of the invention comprise detecting specific protein markers in a tissue of interest, wherein the detected levels thereof may be indicative of pre-cancerous or cancerous tissue, or the stage or prognosis of a cancer. Further provided are methods of treating cancer, and cancer detection kits.

Abstract: The invention provides methods of detecting a change in cell growth patterns.

Abstract: The invention provides compositions and methods of use to enhance reprogramming of mammalian cells. Certain compositions and methods of the invention are of use to enhance generation of induced pluripotent stem cells by reprogramming somatic cells. Certain compositions and methods of the invention are of use to enhance reprogramming of pluripotent mammalian cells to a differentiated cell type. Certain compositions and methods of the invention are of use to enhance reprogramming of differentiated mammalian cells of a first cell type to differentiated mammalian cells of a second differentiated cell type. The reprogrammed somatic cells are useful for a number of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that enhances or contributes to reprogramming mammalian cells. Certain of the inventive compositions and methods relate to inhibiting histone methylation.

Abstract: This invention provides modified nucleotide sequences encoding luciferase that have greater expression than wild type luciferase.

Abstract: The present invention relates to agents, and methods for identifying compounds, which agents and compounds result in the stabilization of mast cells, in particular that inhibit mast cell degranulation. In addition, the invention relates to compositions and methods for the use thereof in treating conditions that are characterized by mast cell degranulation and/or inflammation, including allergic rhinitis.

Abstract: The present invention relates to a recombinant E. coli exhibiting a complex phenotype, comprising one or more RNA polymerase subunit genes, one or more functional genes, and, optionally, one or more transcription factors from a heterologous prokaryote. Also provided are methods for screening such a recombinant E. coli.

Abstract: The present invention relates to methods for detecting for the presence of an agent that putatively causes or potentiates DNA damage comprising subjecting a cell (containing a DNA sequence encoding Gaussia luciferase (GLuc) reporter protein operatively linked to a human GADD45? gene promoter and a human GADD45? gene regulatory element arranged to activate expression of the DNA sequence in response to DNA damage) to an agent; and monitoring the expression of the GLuc reporter protein from the cell. The invention also concerns expression cassettes, vectors and cells which may be used according to such a method and also modified media that may be employed in assays and in preferred embodiments of the method of the invention.

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: Disclosed herein are methods to assess the biological safety of an agent. The method involves contacting one or more test agents to a culture of C. elegans and analyzing the culture for meiotic disruption, wherein an increase in meiotic disruption of the C. elegans, indicates that the test agent(s) has reduced biological safety to mammals. An increase in meiotic disruption of the C. elegans also indicates a likelihood that the test agent is a reproductive toxicant in higher animals, such as humans. Also disclosed are methods to identifying disruptors of fat homeostasis in a mammal. The method involves contacting one or more test agents to a culture of C. elegans and analyzing the culture for fat content, wherein a change in the fat content, as compared to an appropriate control, indicates that the test agent(s) is a likely disruptor of mammalian fat homeostasis.

Abstract: Disclosed are compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically related to GPR35, and/or GPR35-hERG signaling complex. For example, disclosed are compounds for preventing and/or treating diseases which are pathophysiologically related to GPR35 in a subject.

Abstract: MicroRNA (miRNA) profiling of cells showed unique miRNA signatures for each of three Akt isoforms. Among differentially regulated miRNA species, the miR-200 family was downregulated in Akt2-expressing cells. Akt1 knockdown inhibited expression of miR-200 and promoted TGF?-induced epithelial-mesenchymal-transition (EMT) and a stem cell like phenotype. Carcinomas developing in MMTV-cErb2/Akt1?/? mice exhibited increased invasiveness because of EMT induced by miR-200 downregulation. EMT was found to be controlled by miRNA species that are regulated by the balance between Akt1 and Akt2, rather than overall Akt levels.

Abstract: Described are methods relating to assessing antitargets of molecules. Also described are methods of screening molecules. In some aspects of the methods, the molecules are analyzed using a label free biosensor.

Abstract: The invention provides growth selection methods for screening an environmental or a mixed population library of nucleic acids comprising uncharacterized nucleic acids for the presence of a nucleic acid encoding an enzyme of interest. In one aspect, methods for screening and identification of enzymes, e.g., transaminases, nitrilases, aldolases, epoxide hydrolases are provided. Methods for the production and screening of gene libraries generated from nucleic acids isolated from more than one organism for enzymes of interest, e.g., transaminases, nitrilases, aldolases, epoxide hydrolases, are also provided.

Abstract: High-throughput methods of screening agents for activities affecting renal, cardiac, blood or lymphatic vascular development and functions in amphibians in multiwell plates are provided. Also provided are novel compounds that modulate blood and lymphatic vascular development.

Abstract: Genome-wide association studies (GWAS) was recently used to identify SNPs in a genomic region on chromosome 4 that associate with serum urate levels and gout. The present disclosure shows that human ATP-binding cassette, subfamily G, 2 (ABCG2), encoded by the ABCG2 gene contained in this region, is a hitherto unknown urate efflux transporter. The present disclosure further shows that native ABCG2 is located in the brush border membrane of kidney proximal tubule cells, where it mediates renal urate secretion. Introduction of the mutation Q141K encoded by the common SNP rs2231142 by site-directed mutagenesis resulted in reduced urate transport rates compared to wild-type ABCG2. Data from a population-based study of 14,783 individuals support rs2231142 as the causal variant in the region and show highly significant associations with urate levels and gout.

Abstract: The present invention features methods and compositions for the identification of molecules that facilitate the intracellular delivery of a, e.g., nucleic acid molecule. The methods and compositions of the invention utilize any display methodology wherein a library (e.g., a small molecule or protein library) is coupled to a nucleic acid (e.g., RNA or DNA) that encodes each library member.

Abstract: The present invention identifies a method for investigating the response of a cell membrane-associated protein in a living cell to a drug by labeling the protein with a visual marker, and also selectively labeling the membrane portion of the protein with another visual marker, such that upon exposure of the cell to a stimulus, the translocation of the cell membrane-associated protein may be observed directly.

Abstract: The disclosure relates to compounds and methods of inhibiting type three secretion system effector molecules, to methods of detecting compounds that inhibit Yops translocation, and to methods of treating or preventing infections by administering compounds described herein to a subject in need thereof.

Abstract: The disclosure provides methods and kits for performing automated high-throughput assays to measure bactericidal activity in samples, such as plasma or sera from vaccinated subjects to evaluate the efficacy of vaccines against bacterial pathogens. The method combines obligatory linear-range data analysis, plate sealing and liquid volume handling for all assay steps to provide an automated, high-throughput measurement of bactericidal activity with favorable inter-assay and inter-operator variability.

Abstract: Cells and cell lines that express voltage-gated sodium ion channels (NaV) and methods for using the cells and cell lines are disclosed herein. The NaV-expressing cells and cell lines are useful in cell-based assays, e.g., high throughput screening assays.

Abstract: Therapeutic compositions and methods for treating HIV including identification and manipulation of particular domains associated with immunogenicity.

Abstract: Methods for regulating the expression of Na/K-ATPase and uses thereof, including uses in the diagnosis/prognosis and treatment of cancer, are disclosed.

Abstract: The present invention relates to agents, and methods for identifying compounds, which agents and compounds result in the inhibition of the maturation of dendritic cells. In addition, the invention relates to compositions and methods for the use thereof in treating conditions that are characterized by maturation of dendritic cells including infections, allograft reactions, inflammation, allergic and autoimmune diseases, and cancer.

Abstract: Human pluripotential embryonic stem cell cultures are provided, as are human feeder cells useful for growing the human embryonic stem cells, conditioned medium obtained from cultures of the human feeder cells, and factors derived from the conditioned medium. Also provided are methods of growing human embryonic stem cells in the presence of the human feeder cells, the conditioned medium, the factors derived from the conditioned medium, or a combination thereof. In addition to the human embryonic stem cell cultures grown according to such methods, isolated human embryonic stem cells obtained from such human embryonic stem cell cultures are provided, as are methods of using such isolated cells.

Abstract: Stable cell lines which produce the pathological form of PrP after infection with the infectious agent for CJD provide a high throughput assay to identify suitable treatment protocols and compositions. The stable cell lines also provide rich source of infectious CJD agent. They also may be used to identify vaccine candidates. Co-culture of neuronal cells with cells to be tested for infection with a TSE agent also provides a high throughput method for identifying infected cells.

Abstract: Disclosed is a system for detecting a protease inside a cell. In one embodiment, the system includes a chimeric protein that comprises as covalently linked components: 1) at least one optionally masked signal protein; 2) at least one protease-specific cleavage site; and 3) at least one detectable amino acid sequence. The invention has a wide spectrum of applications including use in the detection of novel protease inhibitors inside cells and tissue.

Abstract: The invention in some aspects relates to methods, devices and compositions for evaluating material properties, such as mechanical and rheological properties of substances, particularly biological substances, such as cells, tissues, and biological fluids. In some aspects, the invention relates to methods, devices and compositions for evaluating material properties of deformable objects, such as cells. In further aspects, the invention relates to methods, devices and compositions for diagnosing and/or characterizing disease based on material properties of biological cells.

Abstract: Methods for identifying modulators of gastroesophageal smooth muscle relaxation include isolating various types of smooth muscle fibers from the stomach or esophagus and inducing the fibers to contract. The isolated and contracted fibers are used to screen test compounds for the compound's capacity to modulate relaxation of the smooth muscle fibers. In addition, newly identified unique nicotinic acetylcholine receptors are expressed in a cell, and used to screen test compounds for the compound's capacity to modulate the biological activity of the receptors.

Abstract: A method of ascertaining the bio-safety of an agent is disclosed.

Abstract: Inhibitors of the tmRNA pathway have antibacterial activity with broad species specificity, including B. anthracis and other pathogens of military and civilian interest. Identified cyclic or linear peptides are further selected by in vivo selection methods, kill bacterial pathogens when added exogenously, and/or eliminate plasmids carrying antibiotic resistance or virulence genes. The molecular target of each cyclic peptide is in the tmRNA pathway and the tmRNA pathway is inhibited in vitro and in vivo by the addition of the peptides.

Abstract: Methods and compositions are provided for the screening of candidate agents for their effect on the growth and colonization of hosts by anaerobic microorganisms, particularly microorganisms that comprise the gut microbiota of mammals. In some embodiments of the invention, candidate agents are screened for the ability to modulate growth of multiple microbes within a taxon, or functionally related microbes. In some embodiments of the invention, candidate agents are screened for the ability to modulate growth across a genus or functionally-defined group when the microorganisms are presented with a substrate of interest, which substrates include, without limitation, prebiotic compounds that promote expansion of divergent taxa within the microbiota, e.g. starch, fats, isoflavones, etc.

Abstract: This invention relates to novel rationale and methods for identifying human and primate taste-specific genes, including genes involved in salty taste perception, especially human salty taste perception, but also genes involved in sweet, bitter, umami, and sour taste perception, and genes involved in other taste cell or taste receptor related activities such as digestive function and digestive related diseases, taste cell turnover, immunoregulation of the oral and digestive tract, and metabolic regulation such as in diabetes and obesity, the genes identified using these methods, and assays for identifying taste modulators (enhancers or blockers) and potential therapeutics using these genes. These compounds have potential application in modulating (enhancing or blocking) taste perception, especially salty taste perception and as potential therapeutics.

Abstract: The invention relates to a method and to a substrate for selecting and specifically influencing the function of cells by the adhesion thereof to substrate surfaces having prescribed properties. Said substrates comprise various surface regions each representing a condition affecting the cell adhesion and/or cell function, and said conditions are determined by a geometric property and/or a mechanical property or a combination of a geometric property and/or a mechanical property with a chemical property of each surface region. The invention further relates to analysis devices and to analysis methods using said substrates for identifying and selecting particular cell types, for identifying suitable substrate conditions for affecting a particular cell function or particular cell type or for identifying disease states characterized by a change in the cell type or cell function.

Abstract: An integrated imaging system, e.g., a microsystem, for detecting activity of a biological target, for example, in response to a stimulus, includes an array of pixels arranged on a substrate, each pixel including a photodetector disposed to be in optical communication with a biological target on a surface of the substrate; and at least first and second electrodes arranged in electrical communication with the biological target.

Abstract: The present invention provides methods for the identification of CD4+ T-cell epitopes in the sequences of various proteins, namely, human cytokines and cytokine receptors, as well as the production of peptides which when incorporated into the protein sequence, are no longer capable of initiating the CD4+ T-cell response. In some embodiments, the present invention provides means and compositions suitable for reducing the immunogenicity of cytokines and cytokines receptors such as interferon-?, soluble tumor necrosis factor receptor-1, erythoropoietin, and thrombopoietin.

Abstract: Provided herein is, inter alia, methods and compositions useful in therapeutic interrogation of complex physiologic pathways by massively parallel and permissive transcriptional screening. Thus, methods and compositions are provided herein that are useful for high-throughput functional analysis of complex, transcriptionally regulated physiological pathways. While examples are provided relating to nuclear receptors, the methods and composition can be generalized and applied to any class of transcription factor or any class of gene product that can regulate the activity of transcription. For example, in addition to nuclear receptors, the methods and compositions provided herein are generally applicable to all known transcription factors and any gene encoded product that modulates said transcription factor activity. Moreover, data obtained through the methods provided herein are directly comparable thereby facilitating high-throughput functional analysis.

Abstract: Methods and compositions for the diagnosis of cancer susceptibilities, defective DNA repair mechanisms and treatments thereof are provided. Among sequences provided here, the FANCD2 gene has been identified, and probes and primers are provided for screening patients in genetic-based tests and for diagnosing Fanconi Anemia and cancer. The FANCD2 gene can be targeted in vivo for preparing experimental mouse models for use in screening new therapeutic agents for treating conditions involving defective DNA repair. The FANCD2 polypeptide has been sequenced and has been shown to exist in two isoforms identified as FANCD2-S and the monoubiquinated FANCD-L form. Antibodies including polyclonal and monoclonal antibodies have been prepared that distinguish the two isoforms and have been used in diagnostic tests to determine whether a subject has an intact Fanconi Anemia/BRCA pathway.

Abstract: A novel method which integrates a “sensitized” chemical genetic high-throughput screen (HTS) with RNA interference (RNAi) screening technology is described herein. The present inventors used this method to identify specific small molecule inhibitors and activators of the Wnt pathway. More particularly, the screening method of the present invention may be used to identify small molecule inhibitors and activators that specifically target the activity of a stabilized pool of ?-catenin. A number of compounds identified using the instant method, are shown herein to be small molecule inhibitors of the Wnt pathway that specifically target the activity of the stabilized pool of ?-cat. The inhibitors identified by the present method may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cancer, and others.

Abstract: Multi-well plates having contoured well designs allow multi-stage high throughput parallel assaying of ion channels or ion transporters. A well of a multi-well plate has a bottom region that is sized and shaped to simultaneous accommodate a sensing electrode and a pipette for delivering, e.g., test compounds, wash fluid, and optionally ligands. Such multi-well plates may be coupled with an instrument having a pipette head and an electrode plate. Such arrangement facilitates fluidic contact between cells and fluids provided via a pipette. It also facilitates washing of wells with buffers or other wash solutions to allow serial exposure of test cells to various reagents or other stimuli. Generally, the design allows control and test experiments to be performed on the same cell (or cells) in a single well.

Abstract: The present invention relates to a convenient, flexible and cost-efficient technology for detection and resistance-profiling of bacteria, enabling effective, evidence-based treatment of infections. The invention provides methods and modular kits for the rapid and direct detection of beta-lactam resistant bacteria in a test sample, and optionally for susceptibility profiling of the bacteria, by directly determining hydrolysis product/s of beta-lactam antibiotic substrates in the tested sample. The invention also provides methods and modular kits for the rapid and direct detection of the presence of multidrug resistant bacteria in a test sample.

Abstract: A method is provided for screening the sensitizing properties of chemical compounds. The method is based on keratinocytes or cells that share important hallmarks of these cells, but other components e.g. proteins could also be used. This method is of importance for several conditions, including but not limited to allergic contact dermatitis (ACD), drug hypersensitivity reactions (DHRs) and autoimmune diseases.