Abstract: The present invention relates to agents, and methods for identifying compounds, which agents and compounds result in the modulation of cellular trafficking of proteins in particular that of CF-associated mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). In addition, the invention relates to compositions and methods for the use thereof in treating conditions that are characterized by an ER-associated protein misfolding and abnormal cellular trafficking of disease-associated proteins, including cystic fibrosis (CF).

Abstract: It is an object of the present invention to provide a method for producing pluripotent cells that are free of the risk of cellular canceration and that can be applied to regenerative medicine with a high degree of safety. The present invention provides a method for producing pluripotent cells from somatic cells comprising a step of bringing bacteria having fermentation ability or a component or secretory product thereof into contact with somatic cells.

Abstract: Described are methods for early noninvasive or minimally invasive detection of pathological changes in organ systems/organs/tissues/cells by quantifying organ system-/organ-/tissue-/cells type-enriched miRNA in bodily fluids.

Abstract: The present invention relates to a method of analysing a blood sample of a subject carrying a foetus for the presence of a foetal disease or condition marker, said method comprising the steps of a) extracting nucleic acid from anucleated blood cells, preferably thrombocytes, in said blood sample to provide an anucleated blood cell-extracted nucleic acid fraction, and b) analysing said anucleated blood cell-extracted nucleic acid fraction for the presence of a foetal disease or condition marker, wherein said foetal disease or condition marker is a nucleic acid of a foetus, or wherein said foetal disease or condition marker is a foetal disease or condition-specific expression profile of genes of a cell of said foetus.

Abstract: The present invention relates to a method of regulating or inducing specific physiological conditions or functions using one or more materials displayed on a nano-assembly matrix at high density in cells or in vivo. Specifically, the present invention relates to a method of effectively inducing specific physiological regulation in cells or in vivo by the high-density display of bioactive materials. According to the method of the invention, physiological regulation in cells or in vivo can be optionally induced by regulating the assembly and disassembly of nano assembly (unit) matrix or the display or trapping of specific materials on nano assembly (unit) matrix.

Abstract: This invention provides the use of AChE as nuclease. The use of AChE in regulating the stability of nucleic acid and cell apoptosis, as well as a series of agents based on the use, including the agents for promoting or inhibiting cell apoptosis, the agents for inhibiting tumors, and the agents for protecting nucleic acid from impairing, are provided.

Abstract: Methods of identifying a xenohormetic induced phenotype in an organism are provided. Also provided are methods if using organisms having a known xenohormetically induced phenotype in a number of different applications, such as the identification of xenohormetic agents and the generation of chemical entities and foodstuffs under specific conditions of production governed by xenohormetic effects.

Abstract: The present invention relates to a method for the early diagnosis of a clinically latent placental insufficiency in pathological placental maturation, and the prophylaxis of an intrauterine fetal hypoxia/asphyxia at the due date or after a prolonged gestation, comprising determining the amount and/or the concentration of the biomarker prokineticin 1 (EG-VEGF) and/or its receptor PKR1 and/or PKR2 in a sample from the pregnant subject and/or the pregnancy. In a preferred embodiment, the invention is based on determining the ratio of the amount and/or the concentration of bFGF/PK1 as a measure of current functional condition and an indicator of latent clinical problems such as placental dysfunction resulting in fetal hypoxia.

Abstract: The present invention relates to regulation of cardiac contractile function. The present invention is based on the discovery that microRNAs contribute to the loss of cardiac contractility. Specifically, miR-25 binds to SERCA2a which results in a loss of function and interferes with Ca2+ handling. Accordingly, the present invention relates to methods of increasing cardiac contractile function by inhibiting miR-25. The invention further provides methods to identify agents that can modulate miR-25 activity, including high throughput screening methods, and provides a means to identify agents that are useful for treating patients having cardiac contractile function associated disorders.

Abstract: Provided are methods and compositions useful in the diagnosis, treatment, and monitoring of osteosarcoma. Antisense to certain microRNA (miRNA) found to be associated with cancer stem cells (CSCs) or tumor-initiating cells (TICs) of osteosarcoma are useful to suppress tumor growth and metastasis, and prolong survival. Antisense oligonucleotides to miR-133a are synergistic in combination with standard chemotherapy such as cisplatin in the treatment of osteosarcoma.

Abstract: The invention concerns in vitro proteomic analysis of cells to determine the sensitizing potential (including allergic potential) of compounds on said cells. Several protein markers are provided that allow assays to be performed to determine whether a chemical has a sensitizing potential of contact sensitizers.

Abstract: Provided is a method of decreasing the stability of HER2 (human epidermal growth factor receptor 2) in a cell or individual comprising administering an effective amount of an expression or activity inhibitor of KRT19 (cytokeratin 19) to the cell or individual.

Abstract: The identification and evaluation of mRNA and protein targets associated with mRNP complexes and implicated in the expression of proteins involved in common physiological pathways is described. Effective targets are useful for treating a disease, condition or disorder associated with the physiological pathway.

Abstract: We have discovered that p63 inhibition results in increased cellular proliferation. We have also performed a screen for agents capable of increasing cellular proliferation, (e.g., of stem cells such as skin-derived precursors (SKPs)). The invention therefore invention provides compositions, methods, and kits for increasing proliferation of cells, using compounds that decrease p63 expression or activity or using the compounds described herein. The invention also features methods of using these compounds for increasing hair growth, improving skin health, or promoting skin repair in a subject.

Abstract: The present invention relates to a pharmaceutical composition or an anticancer agent for preventing and treating non-small cell lung cancer, containing a substance for regulating the expression or activity of transmembrane 4 L six family member 4 (TM4SF4). More specifically, the present invention relates to a use of a substance for regulating the expression or activity of TM4SF4 as an anticancer drug or an anticancer agent with respect to non-small cell lung cancer, wherein it was ascertained that it is possible to decrease the growth, metastasis, and infiltration of adenocarcinoma cells and radioresistance by decreasing the expression of TM4SF4 in adenocarcinoma among non-small cell lung cancers and to decrease the growth, metastasis, and infiltration of the cells and radioresistance by increasing the expression of TM4SF4 in other non-small cell lung cancers except adenocarcinoma.

Abstract: The present invention provides modular extracellular sensors, nucleic acids encoding such sensors, and cells expressing such sensors, and methods of employing such sensors and cells for detecting extracellular ligands. In certain embodiments, the extracellular sensors comprise a ligand binding domain, a transmembrane domain, a protease domain, a protease cleavage site, and a transcription factor. In other embodiments, a pair of extracellular receptors is provided where both receptors contain a ligand binding domain and transmembrane domain, and one receptor contains a protease cleavage site and a transcription factor and the other receptor contains a protease domain.

Abstract: This invention relates generally to a novel serine/threonine protein kinase, specifically to hormonally up-regulated, neu-tumor-associated kinase (HUNK); and to the role of HUNK in tumor metastasis, primary tumor development, and the prediction of tumor behavior.

Abstract: A method is described for using ROR gamma t or ROR alpha to diagnose acne and/or to screen inhibitors of Th17 differentiation. Specifically described are methods of inhibiting ROR gamma t or ROR alpha and use of the screened inhibitors in acne treatment.

Abstract: The present invention regards nanoparticles comprising a sterol and a component derived from Quillaja saponaria Molina selected from quillaja acid and quillaja saponin, which nanoparticles do not comprise a phospholipid. It also relates to a composition comprising the nanoparticles, and the use thereof as adjuvant, especially in vaccines, as carriers for amphipathic or hydrophobic molecules and as agents for treatment of cancer. Further, it regards a method for producing the phospholipid-free nanoparticles, a method for the treatment of cancer and a method for assessing the applicability of the cancer treating method.

Abstract: Provided is a method for identifying and suppressing abnormal growth of fibroblasts at an early stage. Provided is a method for identifying the growth state of fibroblasts using as an index the level of expression of ETFB (electron transfer flavoprotein beta subunit), comprising: judging, in cases where the level of expression of ETFB is high, that there is a high probability that fibroblasts are abnormally growing; and judging, in cases where the level of expression of ETFB is low, that there is a high probability that fibroblasts are normally growing. Further, by inhibition of ETFB, abnormal growth of fibroblasts can be suppressed.

Abstract: The invention provides an isolated nucleic acid having a sequence encoding a spermidine/spermine acetyltransferase (“SSAT”), wherein translation of an mRNA comprising the encoded SSAT has increased basal translation and increased stimulated translation, compared to a wild-type mRNA encoding SSAT. Methods of use for the nucleic acid are also provided. Methods and compositions are also provided for reducing ischemia-reperfusion injury in organs or tissue for transplantation.

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: A cellular model is described for targeting dysregulation or inappropriate activation of the Sonic Hedgehog/Patched (SHH/PTCH) pathway. Also described, is a screening method using this cellular mod& to screen for pharmacological compounds that can treat or prevent skin cancer and, in particular, Basal Cell Carinoma (BCC) lesions.

Abstract: The present disclosure is directed to methods of diagnosing a neurodegenerative condition, such as Alzheimer's disease, comprising contacting a cell sample from a subject with at least one stimulus, such as a protein and/or polysaccharide mixture, a protein kinase C activator, an A? oligomer, an agent, and combinations thereof; and detecting the expression of at least one gene in the cell sample. Methods may further comprise comparing the expression of the at least one gene in the cell sample to the expression of the same at least one gene in control cells; and determining whether the subject has the neurodegenerative condition (e.g., Alzheimer's disease), wherein a change in the expression of the at least one gene in the cell sample compared to the expression of the same at least one gene in the control cells indicates the subject has the neurodegenerative condition (e.g., Alzheimer's disease).

Abstract: The invention relates to compounds of formula (I), and the use thereof as a drug, particularly for the treatment of tumors associated with hyperactivation of the hedgehog protein signaling pathway, treatment of neurodegenerative diseases, treatment of diseases related to cerebral development (holoprosencephaly), for stem cell monitoring treatment of cerebrovascular accidents and cardiovascular accidents, treatment of diseases involving oligodendrocytes and diseases involving neurolemmocytes, for application thereof in vitro for modulating human or animal stem cell renewal, and for the treatment of diabetes. The invention also relates to pharmaceutical compositions having a compound of formula (I).

Abstract: In one aspect, the invention relates to methods for treating muscle atrophy by providing to an animal in need thereof an effective amount of a compound. The compound can modulate the expression levels of multiple mRNA of a muscle atrophy signature. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: AnnexinA2 (ANXA2), a member of the Annexin family of calcium-dependent, phospholipid binding proteins, is one of a panel of identified antigens recognized by the post-vaccination sera of patients who demonstrated prolonged disease-free survival following multiple vaccinations. AnnexinA2 is abundantly expressed in pancreatic adenocarcinomas and cell surface/membrane AnnexinA2 increases with the progression from premalignant lesions to invasive pancreatic adenocarcinomas. The cytoplasmic to cell surface translocation of AnnexinA2 expression is critical for pancreatic cancer cell invasion. In addition, phosphorylation of AnnexinA2 at Tyrosine 23 is important for its localization to the cell surface and for the invasion of pancreatic cancer cells. Finally, loss of AnnexinA2 leads to the loss of the Epithelial-Mesenchymal Transition.

Abstract: The present invention relates to a composition useful for the diagnosis of diseases associated with aberrant expression of the genes encoding the secreted proteins Futrin 1, 2, 3 and/or 4 (=R-Spondin 2, 3, 1 and 4, respectively), e.g. in connection with tumors or diseases of the muscle, kidneys or bones. The present invention also relates to a pharmaceutical composition containing a compound which is capable of modifying (a) the expression of the gene encoding Futrin 1, 2, 3 and/or 4 or (b) the activity of the Futrin 1, 2, 3 and/or 4 protein.

Abstract: The present disclosure relates to an Extra Cellular Matrix composition specific for cancer type and a tumor microenvironment platform for long term culturing of tumor tissue, wherein said culturing provides human ligands and tumor tissue micro-environment to mimic physiologically relevant signalling systems. The present disclosure further relates to the development of a Clinical Response Predictor and its application in the prognostic field (selection of treatment option for the patient) and translational biology field (development of anticancer drugs). The disclosure further relates to a method of predicting clinical response of a tumor patient to drug(s). The disclosure further relates to a method for screening tumor cells for the presence of specific markers for determining the viability of said cells for indication of tumor status.

Abstract: The present application provides novel human genes A7322, whose expression is markedly elevated in breast cancer. The present application also provides human genes F3374 whose expression is markedly elevated in breast cancer. These genes and polypeptides encoded thereby can be used, for example, in the diagnosis of breast cancer, and as target molecules for developing drugs against breast cancer. The invention features methods of screening for modulators of the kinase activity of PBK/TOPK. The invention further provides methods of screening for agents to prevent or treat cancer, such as breast cancer.

Abstract: The present invention relates to microRNAs (miRNAs) that are associated with obesity. The present invention is directed to methods, compounds, and compositions for preventing and treating obesity, as well as related diseases, using a microRNA inhibitor.

Abstract: A method is described for using IL-12R 1/IL-23R, CCR6, BATF, AHR, STAT3, IRF4 crucial actors in Th17 cells differentiation as markers for acne. Also described are method of their use to diagnose acne, to screen inhibitors of Th17 differentiation. In particular, methods are described for inhibiting IL12R 1/IL-23R, CCR6, BATF, AHR, STAT3, IRF4 and the use of these screened inhibitors in acne treatment.

Abstract: Antimicrobial compositions including a cell penetrating peptide (CPP) having the amino acid sequence Tyr-Ala-Arg-Val-Arg-Arg-Arg-Gly-Pro-Arg-Gly-Tyr-Ala-Arg-Val-Arg-Arg-Arg-Gly-Pro-Arg-Arg (SEQ ID NO:1) or variant thereof are disclosed. The CPP, which itself has antimicrobial properties, can be advantageously combined with or conjugated to a cargo to increase the delivery, efficacy, or combinations thereof, of the cargo into cells. In preferred embodiments, the CPP is combined with or conjugated to a functional nucleic acid, such as an external guide sequence (EGS) which can target and reduce expression of essential microbial genes or genes than impart resistance to antimicrobial drugs. Methods of using the compositions alone or in combination with traditional antimicrobial drugs to treat infections are also disclosed.

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: Provided herein are methods, kits and compositions to classify fungi. Methods are provided for classification of fungi according to established phenotypes, for example, antimicrobial susceptibility profiles. More specifically, the invention provides methods for the use of PNA probes in diagnostic applications, which will aid in the direction of appropriate therapy against fungi.

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 invention relates to IHG-1 (induced by high glucose-1) a novel gene which encodes a protein that amplifies fibrotic responses in in vitro and in vivo models of fibrotic disorders and in human diabetic nephropathy. In particular the invention relates to modifications of the IHG-1 structure which are potential fibrosuppressant biotherapeutics and modify cellular invasiveness. The invention also relates to a method of screening a therapeutic agent for suitability for the treatment of fibrotic disease comprising testing a candidate therapeutic agent for the ability to reduce the expression of IHG-1 levels in a model system.

Abstract: The invention features methods of diagnosing cancer in a mammal (e.g., a human) by detecting a biomarker selected from a satellite II ribonucleic acid (RNA) molecule, a cancer-associated polycomb group (CAP) body, a cancer-associated satellite transcript (CAST) body, and UbH2A. Also featured is a method for identifying an agent for treating cancer in a mammal by contacting a cancer cell having a biomarker selected from a CAP body, a CAST body, and a satellite II RNA molecule with a test agent and determining whether the test agent reduces the level of the biomarker in the cancer cell. Other inventions featured are a method for determining whether a chemotherapeutic agent increases epigenetic imbalance of a cell and a method for detecting epigenetic imbalance by determining a copy number of a satellite II DNA locus at chromosome 1q12 in a cell.

Abstract: The present invention relates to a method for determining whether a cancer patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor, comprising detecting the expression of the E-cadherin protein in a cancer sample of said cancer patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. Said detection of the expression of the E-cadherin protein in a cancer sample of a cancer patient is preferably conducted by way of an immunohistochemistry (IHC) method. Said IHC method preferably employs a primary antibody which is specific for E-cadherin and a secondary antibody which specifically reacts with the primary antibody. The present invention also relates to a method of treating a cancer patient whose cancer is characterized by an E-cadherin protein immunoreactivity score (IRS) of 0-2, comprising administering to the patient a therapeutically effective amount of a PTK2 inhibitor.

Abstract: The invention provides methods for predicting the efficacy of anti-TNF and anti-IL17 combination therapies in the treatment of a subject suffering from inflammatory disease by determining the level CXCL1 and/or CXCL5 markers in a sample derived from the subject.

Abstract: Provided herein are methods of promoting cell fate change, particularly differentiation of tumor cells, by inhibition of USP1, UAF1, and/or ID (e.g., ID1, ID2, and/or ID3).

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 and to methods for the detection of such oligodeoxynucleotides.

Abstract: Obesity is associated with a state of chronic low-grade inflammation and the present invention establishes that adipose-resident natural killer T (NKT) cells attenuate inflammation in adipose tissue and improves systemic glucose homeostasis in mice at different stages of obesity. Accordingly, the present invention provides methods of treating type-2 diabetes or those at risk for type-2 diabetes using activators of adipose-resident NKT cells. Such activators include particular glycolipids (e.g., a-galactosyl-ceramide and its analogs other than sulfated analogs) and cytokines that promote M2 macrophage polarization. The invention also includes methods to screen for activators of adipose-resident NKT cells.

Abstract: The invention relates to the control of gene expression. Specifically, the invention provides compositions and methods for the production and use of recombinant nucleic acid molecules that have the ability to specifically downregulate an expressed target gene in vivo. In some aspects, the invention provides methods for producing a hairpin DNA molecule where part of the molecule is derived from an mRNA that is a target for a small interfering RNA (siRNA) derived from the hairpin. In other aspects, the invention provides synthetic hairpin adapter oligonucleotides that are used in the construction of siRNA-producing cassettes. In other aspects, the invention provides methods for testing for the presence or absence of specific inhibitory activity of an RNAi trigger molecule, and in still other aspects, the invention provides methods for identifying an active RNAi trigger molecule from a library of RNAi trigger molecules.

Abstract: Methods and means are provided for monitoring and modulating reduction of gene expression in eukaryotic organisms, using double stranded RNA comprising, in addition to the dsRNA region comprising nucleotide sequences homologous to the target gene, additional dsRNA regions designed to down regulate a second gene or which are unrelated to the target gene.

Abstract: The invention is in the field of genomics and it provides an in vitro method for predicting whether a compound is genotoxic in vivo. In particular, the invention provides a method for predicting the in vivo genotoxicity of a compound comprising the steps of performing an Ames test on the compound and determining if the result is positive or negative, followed by a step wherein the gene expression of at least 3 genes is determined in a HepG2 cell, compared to a reference value and predicting that the compound is in vivo genotoxic if the expression level of more than 2 of the genes is above a reference value.

Abstract: The present invention provides a process for characterizing a glatiramer acetate related drug substance or drug product comprising the steps of: a) obtaining a batch of the glatiramer acetate related drug substance or drug product; b) immunizing a mammal with a predetermined amount of a glatiramer acetate related drug substance or drug product; c) preparing a culture of cells from the mammal of step b) at a predetermined time after immunization; d) incubating cells from the culture of step c) with a predetermined amount of the glatiramer acetate drug related substance or drug product of step a); and e) determining the level of expression of at least one gene disclosed herein or determining the level of biological activity of the cells of step c) as disclosed herein, thereby characterizing the glatiramer acetate related drug substance or drug product of step a).

Abstract: A novel genetic factor for rheumatoid arthritis is searched for and used as a diagnostic marker. A method of testing for rheumatoid arthritis, comprising detecting an autoantibody to myelin basic protein in a biological sample from a subject. A test kit for rheumatoid arthritis, comprising myelin basic protein. A diagnostic marker for rheumatoid arthritis, comprising an antibody to myelin basic protein. A method of judging the risk to develop rheumatoid arthritis, comprising identifying the single nucleotide polymorphism of a nucleotide present in the myelin basic protein gene of a subject or identifying the single nucleotide polymorphism of a nucleotide that is in linkage disequilibrium with the first mentioned nucleotide.

Abstract: The methods described herein enable the evaluation of compounds on subjects to assess their therapeutic efficacy or toxic effects. The target of analysis is the underlying biochemical process or processes (i.e., metabolic process) thought to be involved in disease pathogenesis. Molecular flux rates within the one or more biochemical processes serve as biomarkers and are quantitated and compared with the molecular flux rates (i.e., biomarker) from control subjects (i.e., subjects not exposed to the compounds). Any change in the biomarker in the subject relative to the biomarker in the control subject provides the necessary information to evaluate therapeutic efficacy of an administered drug or a toxic effect and to develop the compound further if desired. In one aspect of the invention, stable isotope-labeled substrate molecules are administered to a subject and the label is incorporated into targeted molecules in a manner that reveals molecular flux rates through one or more metabolic pathways of interest.

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.