Abstract: Disclosed are methods for identification of agents that modulate cell attachment, cell migration and cell viability. Cancer and primary cells adhered to a matrix are treated with agent(s) that modulate ActRII signaling and cell adhesion. Agents are tested that modulate cell adhesion, detachment, invasion and viability. Agents that modulate the expression, phosphorylation, function and translocation of ActRII signaling pathway members also can predict agents that modulate cell adhesion, detachment, invasion and viability. The methods have utility in tissue engineering as well as identifying agents that prevent cancer cell metastasis, wound dehiscence, aortic dissection and aid retina attachment and skin replacement and fertility. Examples of tissue engineering include techniques that allow for the generation of biological substitutes that restore, maintain, or improve tissue function or a whole organ.

Abstract: Methods and compositions relating to diagnosing and treating a VMAT-2 deficiency disease are described. Provided are methods for screening for, diagnosing or detecting a risk of developing a VMAT-2 deficiency disease comprising detecting the presence of a VMAT-2 variant in a sample of a subject, wherein the presence of the VMAT-2 variant is indicative that the subject has a VMAT-2 deficiency disease or an increased risk of developing a VMAT-2 deficiency disease compared to an individual having wild type VMAT-2. Also provided are methods of treating a VMAT-2 deficiency disease with a dopamine agonist.

Abstract: The invention relates to a method of screening for a compound useful in the treatment of a disease selected from neurodegenerative diseases and neuro-inflammatory diseases, said method comprising providing a test cell; staining at least one organelle of said test cell; contacting said test cell with a test compound; and recording the path of said stained organelle in said test cell. Suitable compounds are identified from a comparison of the recorded path with a suitable reference.

Abstract: Human CDK9 genes are identified as modulators of the IGF pathway, and thus are therapeutic targets for disorders associated with defective IGF function. Methods for identifying modulators of IGF, comprising screening for agents that modulate the activity of CDK9 are provided.

Abstract: The present invention provides compounds and assays for the identification and validation of compounds for use in the treatment of muscular mystrophy (MD), or a form thereof, in which said compounds increase the post-transcriptional expression of a target gene (i.e., mIGF1, ITGA7, or UTRN).

Abstract: A variety of methods, devices and compositions are implemented for light-activated molecules. One such method is implemented for generating secondary messengers in a cell. A nucleotide sequence for expressing a chimeric light responsive membrane protein (e.g., rhodopsin) is modified with one or more heterologous receptor subunits {e.g., an adrenergic receptor (alpha1, Beta2)}. The light responsive membrane protein is expressed in a cell for producing a secondary messenger in response to light.

Abstract: A metabolically engineered E. coli strain which produces sialic acid and a method of making said strain. In the engineered E. coli cells, the nanT (sialic acid transporter) and nanA (sialic acid adolase) genes are inactivated, and the neuC and neuB genes of sialic acid biosynthesis in Neisseria meningitidis group B are introduced and overexpressed in the nanT? nanA? E. coli cell. In addition, the glucosamine synthase gene, glmS, of E. coli is co-overexpressed with neuB and neuC.

Abstract: The present invention is based upon the identification of regions within the NOTCH-1 receptor that, when mutated, lead to increase receptor signaling. The mutations are associated with uncontrolled cellular growth and this growth may be arrested using agents that interfere with NOTCH-1 activity, such as inhibitors of gamma-secretase. Assays for the NOTCH-1 mutations may be used diagnostically or as part of a treatment regimen for cancer patients.

Abstract: The present invention provides a kit comprising a cell transfected with hepatic transcription regulators, and a culture medium that support growth of the cell. The present invention further provides a method for determining drug metabolism and predicting drug toxicity, comprising transfecting a cell with hepatic transcription regulators, and culturing the cell on a medium.

Abstract: A method of detecting and isolating cells that produce a secreted protein of interest (POI) that has an immunoglobulin CH3 domain and/or substituted CH3 domain, comprising: a) constructing a cell line transiently or stably expressing a cell surface capture molecule, which binds the POI, by transfecting the cell line with a nucleic acid that encodes such cell surface capture molecule; b) transfecting said cell simultaneously or subsequently with a second nucleic acid that encodes a POI wherein such POI is secreted; c) detecting the surface-displayed POI by contacting the cells with a detection molecule, which binds the POI; and d) isolating cells based on the detection molecule.

Abstract: A method of detecting and isolating cells that produce a secreted protein of interest (POI) that has an immunoglobulin CH3 domain and/or substituted CH3 domain, comprising: a) constructing a cell line transiently or stably expressing a cell surface capture molecule, which binds the POI, by transfecting the cell line with a nucleic acid that encodes such cell surface capture molecule; b) transfecting said cell simultaneously or subsequently with a second nucleic acid that encodes a POI wherein such POI is secreted; c) detecting the surface-displayed POI by contacting the cells with a detection molecule, which binds the POI; and d) isolating cells based on the detection molecule.

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 instant invention relates to the use of 24-hydroxylated vitamin D compounds as therapeutics in mammalian bone fracture repair. In addition, the instant invention relates to novel 24-hydroxylated vitamin D compound receptors which can be employed in the development of compounds capable of facilitating fracture repair in animals. The instant invention also relates to nucleic acids encoding such receptors as well as vectors, host cells, transgenic animals comprising such nucleic acids and screening assays employing such receptors.

Abstract: The invention provides methods related to evaluating the methylation status of a polynucleotide that includes an internal control.

Abstract: This invention relates to systems and methods for managing livestock, such as cattle, from conception to consumption. More particularly, this invention relates to systems and methods in which users, such as producers, feedlot managers, packers, buyers, sellers, and consumers, are brought together through shared information and improved communication. Users may access one or more applications, tools, and/or systems to increase the value of each animal, monitor and track each animal, and improve the efficiency of their operation.

Abstract: A method of detecting and isolating cells that produce a secreted protein of interest (POI) that has a T cell receptor variable domain, comprising: a) constructing a cell line transiently or stably expressing a cell surface capture molecule, which binds the POI, by transfecting the cell line with a nucleic acid that encodes such cell surface capture molecule; b) transfecting said cell simultaneously or subsequently with a second nucleic acid that encodes a POI wherein such POI is secreted; c) detecting the surface-displayed POI by contacting the cells with a detection molecule, which binds the POI; and d) isolating cells based on the detection molecule.

Abstract: Provided herein are methods of producing an antigen-presenting platelet. Also provided herein are methods of eliciting an immune response in a subject using the antigen-presenting platelets described herein. Also provided are methods of screening for an immune response elicited by an antigen-presenting platelet. Further provided are isolated populations of platelets that present a selected antigen produced by the methods described herein.

Abstract: A variety of methods, devices and compositions are implemented for light-activated molecules. One such method is implemented for generating secondary messengers in a cell. A nucleotide sequence for expressing a chimeric light responsive membrane protein (e.g., rhodopsin) is modified with one or more heterologous receptor subunits {e.g., an adrenergic receptor (alpha1, Beta2)}. The light responsive membrane protein is expressed in a cell for producing a secondary messenger in response to light.

Abstract: The present invention relates to a method for selecting for cells or cell lines that produce a recombinant protein/polypeptide in high yields, the method allowing for the selection of high producer cells or cell lines in an early phase of cell line development, the method comprising the step of determining the nuclear DNA content of the cells or cell lines, wherein the level of the nuclear DNA content of the cells or cell lines positively correlates with the capacity of the cells or cell lines to produce the recombinant protein/polypeptide.

Abstract: The present invention relates to the use of interleukin-15 (IL-15) as selectable marker for gene transfer, preferably of at least one gene of therapeutic interest, into a mammalian cell or cell line, in particular a human cell or cell line. The present invention furthermore relates to transgenic mammalian cells or cell lines expressing IL-15 as selectable marker and co-expressing at least one protein of interest encoded by at least one gene of interest, which is preferably a protein of therapeutic interest. The present invention is in particular suitable for chimeric antigen receptors (CARs) as the gene or protein of interest and their expression in lymphocytes. The transgenic mammalian cells and cell lines are furthermore suitable for use as a medicament, in particular in the treatment of cancer and in immunotherapy, such as adoptive, target-cell specific immunotherapy.

Abstract: In various aspects, the invention provides methods for cyclizing proteins, including methods for enhancing the stability of cyclized proteins under cytosolic conditions. The invention also provides various methods for using the cyclized proteins. For example, cyclized proteins of the invention may be used in screening assays analogous to the yeast two hybrid assay. Selected embodiments of the invention provide cyclized single chain variable fragment (ScFv) molecules, including molecules in the form of an immunoglobulin fold.

Abstract: As a means for treating diseases such as neurodegenerative diseases, malignant tumors and infectious diseases, a method for screening a substance increasing glutathione is provided. According to this method, by contacting a test substance with a cell expressing a GTRAP3-18 protein, a substance decreasing the amount of expression of the GTRAP3-18 protein or inhibiting a function of the GTRAP3-18 protein is specified as a target substance.

Abstract: The present invention relates to markers of endometriosis which are differentially expressed in the endometrial cells of females with endometriosis compared to endometriosis-free females. The invention also relates to methods for determining likelihood of endometriosis in female subjects, to methods for grading endometriosis in females suffering from endometriosis and to methods for treating this disease. The invention is also concerned with polynucleotides, probes, primers and kits useful for reducing into practice the above-mentioned methods which are more rapid, non invasive, much less complicated and much less costly than laparoscopy.

Abstract: The invention provides methods, cells and constructs for optical measurement of membrane potential. These methods can be used in cells that are not accessible to presently available methods using electrodes. The methods can be directed to, for example, high-throughput drug screening assays to determine agents that can affect membrane potential of a target cell.

Abstract: The present invention provides isolated polypeptides having an amino acid sequence having at least 70% identity to SEQ ID NO:20, wherein the polypeptide has ER-?36 activity. The invention further provides methods for identifying agents that bind to such polypeptides, methods for detecting such polypeptides, and methods for altering the activity of such polypeptides. Also provided are antibodies that specifically bind to an amino acid sequence depicted at SEQ ID NO:1, or an immunogenic fragment thereof, and methods for making and using such antibodies.

Abstract: Disclosed herein are magnetotactic algae, such as algae cells that include magnetic nanoparticles. In some examples the magnetotactic algae express a nucleic acid molecule encoding a bacterial MagA ferrous transporter, a nucleic acid molecule encoding a bacterial Mms6 magnetite binding protein, or both. Also disclosed herein are methods for producing magnetotactic algae and methods of producing biofuel or magnetic nanoparticles utilizing magnetotactic algae. Further disclosed herein are methods of enriching a population of magnetotactic algae cells (for example, increasing the number of magnetotactic algae cells in a population of algae cells). In further embodiments, disclosed herein are methods of selecting a transformed algae cell.

Abstract: The present invention provides a method and kit for detection of two or more target molecules in a single tissue sample, such as for gene and protein dual detection in a single tissue sample. Methods comprise treating a tissue sample with a first binding moiety that specifically binds a first target molecule. Methods further comprise treating the tissue sample with a solution containing a soluble electron-rich aromatic compound prior to or concomitantly with contacting the tissue sample with a hapten-labeled binding moiety and detecting a second target molecule. In one example, the first target molecule is a protein and the second is a nucleic acid sequence, the first target molecule being detected by immunohistochemistry and the second by in situ hybridization. The disclosed method reduces background due to non-specific binding of the hapten-labeled specific binding moiety to an insoluble electron rich compound deposited near the first target molecule.

Abstract: A method for detecting a predisposition to breast cancer in a subject is provided. The method includes detecting in a biological sample from the subject one or more polymorphisms in the sequence of CD44 gene. The presence of one or more polymorphisms in the sequence of CD44 gene indicates that the subject has a predisposition for developing breast cancer.

Abstract: The present invention is related to the novel discovery of a number of genes that were identified as systemic markers of pulmonary inflammation. This discovery allows for development of a novel tool for reliable, rapid and efficient assessment of therapeutic responses and enables design of novel therapies targeted against diseases associated with pulmonary inflammation. In one embodiment, the present invention allows quantification of therapeutic response in patients who have a disease associated with pulmonary inflammation. In preferred embodiments, the genes are CD64, ADAM9, CD36, IL32, HPSE, PLXND1, HCA 112, CSPG2, TLR2, and CD163.

Abstract: Peptides for the treatment of inflammation, and therapeutic uses and methods of using the same are disclosed. Peptides including a transducing sequence are effective for inhibiting cytokine activity and TNF-? secretion through interaction with toll-like receptors. Experiments are described illustrating the efficacy of the compounds in treating otitis media.

Abstract: A method of using genetic polymorphisms related to pro-inflammatory mediators to predict clinical outcome in critically ill patients admitted to an ICU is provided.

Abstract: The present invention relates to animal protein-free cell culture media comprising polyamines and a plant- and/or yeast-derived hydrolysate. The invention also relates to animal protein-free culturing processes, wherein cells can be cultivated, propagated and passaged without adding supplementary animal proteins in the culture medium. These processes are useful in cultivating cells, such as recombinant cells or cells infected with a virus, and for producing biological products by cell culture processes.

Abstract: The invention provides polynucleotides and methods for expressing light-activated proteins in animal cells and altering an action potential of the cells by optical stimulation. The invention also provides animal cells and non-human animals comprising cells expressing the light-activated proteins.

Abstract: A method for producing cAMP using a chimeric olfactory receptor. The method includes a step of preparing a reaction system comprising a first layer, a lipid bilayer membrane, and a second layer, and a step of supplying a chemical substance which stimulates the chimeric olfactory receptor to the first layer so as to produce the cAMP from ATP. The lipid bilayer membrane includes the chimeric olfactory receptor and adenylate cyclase. The chimeric olfactory receptor penetrates the lipid bilayer membrane. The second layer contains ATP and a G protein. The G protein is placed in the vicinity of one end of the chimeric olfactory receptor. The chimeric olfactory receptor is derived from a mouse olfactory receptor and the N-terminal of the chimeric olfactory receptor is modified with an amino acid sequence.

Abstract: The present invention describes compositions for both diagnostic and therapeutic applications. In one embodiment, the present invention contemplates a vaccine formulation comprising an antigen and IL12R?1 isoform 2. In some embodiments, this invention relates to a method of quantifying the ratio of IL12R?1 transcript and a splice variant thereof in a sample, including but not limited to at the cDNA level. In other embodiments, this invention relates to a method of augmenting an immune response by administering, inhibiting and/or inducing IL12R?1 isoform 2.

Abstract: The present invention provides methods, kits, and compositions for detecting mutations in transient receptor potential cation channel, subfamily V, member 4 (TRPV4). In particular, mutations are detected in TRPV4 to detect diseases such as scapuloperoneal spinal muscular atrophy (SPSMA) and hereditary motor and sensory neuropathy type IIC (HMSN IIC) or Charcot-Marie-Tooth disease type 2C (CMT2C).

Abstract: The present invention relates to the use of proteins that are differentially expressed in tumor associated stromal cells, as compared to normal stromal, as biomolecular targets for tumor treatment therapies. The present invention also provides compounds and pharmaceutically acceptable compositions for administration in the methods of the invention.

Abstract: The present invention is predicated, in part, on the functional characterisation of membrane bound proteins that contribute to cation flux across biological membranes. In accordance with the present invention, it has been determined that at least some PQ-loop repeat polypeptides contribute to cation flux across biological membranes.

Abstract: A method for detecting a predisposition to breast cancer in a subject is provided. The method includes detecting in a biological sample from the subject one or more polymorphisms in the sequence of CD44 gene. The presence of one or more polymorphisms in the sequence of CD44 gene indicates that the subject has a predisposition for developing breast cancer.

Abstract: Keratin 8 and 18 (K8/K18) mutations are shown to be associated with a predisposition to liver or biliary tract disease, particularly noncryptogenic hepatobiliary disease. Unique K8/K18 mutations are shown in patients with diseases including but without limitation to viral hepatitis, biliary atresia, alcoholic cirrhosis and other acute or chronic toxic liver injury, cryptogenic cirrhosis, acute fulminant hepatitis, autoimmune liver disease, cystic fibrosis, primary biliary cirrhosis, primary sclerosing cholangitis, diseases that are linked with cryptogenic cirrhosis, such as nonalcoholic steatohepatitis, and the like. Livers with keratin mutations had increased incidence of cytoplasmic filamentous deposits. Therefore, K8/K18 are susceptibility genes for developing cryptogenic and noncryptogenic forms of liver disease. Mutant alleles are associated with disease susceptibility, and their detection is used in the diagnosis of a predisposition to these conditions.

Abstract: The invention provides methods related to evaluating the methylation status of a polynucleotide that includes an internal control.

Abstract: Binding assays for identifying compounds that modulate human T1R2 polypeptide associated taste are disclosed. These assays detect the specific binding of compounds to a human T1R2 polypeptide or the modulation of the specific binding of a compound that specifically binds to a human T1R2 polypeptide. The binding assays may include the use of detectable labels, e.g., radionuclides, enzymes, fluorophases, and the like. Compounds identified in these binding assays have putative application as T1R2 taste modulators, particularly sweet taste, and potentially are useful additives in compositions for human or animal consumption.

Abstract: Environmentally stable biosensors are disclosed, which comprise a ligand binding domain from a thermophilic organism conjugated to donor and fluorescent moieties that permit detection and measurement of Fluorescence Resonance Energy Transfer upon ligand binding. Such biosensors demonstrate enhanced acid-, thermal- and chemical stability as compared to sensors constructed using protein domains from mesophilic organisms.

Abstract: The present invention relates to a method for identifying a specific type and/or state of a mammalian cell in a sample obtained from a mammal, comprising a) analyzing the relative amount of accessible chromatin in regions that are specific for a cell-type and/or cellular state in the genome of said cell, b) comparing said relative amount of accessible chromatin said in regions with the relative amount of accessible chromatin in regions in the genome of said cell that are unspecific for a cell-type and/or cellular state, and c) deducing the specific type and/or state of said mammalian cell in said sample based on said comparison. Preferably, said identifying further comprises a relative quantification of said specific cell type and/or state based on said comparison. The method can further comprise a diagnosis of a predisposition to a disease or a disease based on said identification. Kits and certain markers in regions of accessible chromatin in the genome are described, too.

Abstract: Methods for producing membrane-spanning polypeptides in high yields, with native conformation, and/or in soluble form include solubilizing in non-ionic or zwitterionic detergents, as well as use of promoters and expression vectors for expressing high yields of membrane-spanning polypeptides in bacterial cells. Mutated promoters provide tight control of membrane-spanning polypeptides in bacterial cell hosts.

Abstract: The present invention relates to diagnostic and prognostic methods to determine the likelihood of a subject who has a inflammatory disease or liver disease of developing cancer. In particular, the present invention relates to methods for identifying subjects with increased susceptibility to developing cancer, such as hepatocellular carcinoma (HCC) where the subject has an inflammatory disease, such as, but not limited to cirrhosis, by identifying a variance or polymorphism in the human EGF gene. In particular, the methods of the present invention relate to identifying subjects with increased susceptibility to developing cancer such as HCC, where the subject has an inflammatory disease, such as but not limited to cirrhosis, and the subject is identified to have a single nucleotide polymorphism 61A>G in the 5?UTR of the EGF gene.

Abstract: The present invention relates to USP47 (ubiquitin specific protease 47) inhibitors and methods for inducing apoptosis or cell death in a target cell. In certain embodiments, the invention relates to methods and kits to screen for related agents that induce apoptosis. Additionally, the invention relates to assays for screening compounds capable of acting as USP47 inhibitors.

Abstract: The present invention relates to a method for determining a subject's resistance to treatment with 2,2-dimethyl-N-((S)-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl)-N?-(2,2,3,3,3-pentafluoro-propyl)-malonamide by measuring the levels a biomarker or biomarkers present in a biological sample obtained from the subject, the biomarker being IL6 and/or IL8. The present invention also relates to a combination therapy for a patient suffering from a proliferative disorder comprising administering to the patient 2,2-Dimethyl-N-((S)-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl)-N?-(2,2,3,3,3-pentafluoro-propyl)-malonamide and an anti-IL6 and/or an anti-IL8 agent.

Abstract: The present invention provides methods and kits for prognosing the progression of fibrosis in a subject having fibrosis, as well as methods for identifying a compound that can slow down the progression of fibrosis in a subject having fibrosis, methods of monitoring the effectiveness of a therapy in reducing the progression of fibrosis in a subject having fibrosis, methods of selecting a subject for participation in a clinical trial for the treatment of fibrosis, and methods for inhibiting progression of fibrosis in a cell or a subject having fibrosis. The methods are based on determining the level of Toll-like recepter 9 (TLR9).

Abstract: Methods of isolating motile cells of interest from an animal tissue is provided. Also provided are methods of determining mRNA or protein expression of a gene in motile cells of interest from an animal tissue. Additionally, methods of determining whether a cancer in a tissue of a mammal is likely to metastasize are provided. Methods are also provided for inhibiting metastasis of a cancer in a tissue of a mammal. Further provided are methods of determining resistance of a motile cancer cell population in an animal tissue to a chemotherapeutic agent.