Thu, 27 Oct 2016 08:00:00 EDTAs described herein, lactosylceramide (LacCer) levels are up-regulated in the CNS during chronic experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). LacCer acts in an autocrine manner to trigger transcriptional programs that promote the recruitment and activation of CNS infiltrating monocytes and microglia, and neurodegeneration. In addition, increased B4GALT6 expression and LacCer levels were detected in CNS MS lesions in human patients. Finally, the inhibition of LacCer synthesis suppressed local CNS innate immunity and neurodegeneration in EAE, and interfered with the activation of human astrocytes in vitro. Thus, B4GALT6 is a therapeutic target for MS and other neuroinflammatory disorders.
Thu, 27 Oct 2016 08:00:00 EDTThe described invention provides methods for targeting emopamil binding protein (EBP) with small molecules that induce an abnormal feedback response by lowering endogenous cholesterol biosynthesis.
Thu, 27 Oct 2016 08:00:00 EDTCyclic adenosine monophosphate (cAMP) biosensors comprising a Renilla luciferase (RLuc), a green fluorescent protein (GFP), and an exchange protein activated by cAMP, and uses thereof in determining cAMP levels both in vivo and in vitro. Another aspect of the invention relates to methods for controlling blood glucose levels.
Thu, 27 Oct 2016 08:00:00 EDTMethods and compositions for the efficient and accurate determination of HIV susceptibility to an integrase inhibitor and/or HIV replication capacity are provided. In certain aspects, the methods involve detecting in a biological sample a nucleic acid encoding an HIV integrase that comprises a primary mutation at codon 143, wherein the mutation at codon 143 does not encode arginine (R) or cysteine (C), and wherein the presence of the integrase-encoding nucleic acid in the biological sample indicates that the HIV has a decreased susceptibility to an integrase inhibitor or altered replication capacity relative to a reference HIV. In certain embodiments, the HIV also contains one or more secondary mutations in integrase. Also provided are methods for determining the selective advantage of a mutation or mutation profile based on the difficulty to create the mutation, and its effect on susceptibility to an integrase inhibitor or replication capacity.
Thu, 27 Oct 2016 08:00:00 EDTDisclosed herein are chromosomal loci associated with clinical outcome to treatment for multiple myeloma. Genome-wide changes observed in myeloma relate to prognosis and treatment response to a proteasome inhibitor. Compositions and methods are provided to assess DNA copy number at corresponding to markers of loci and genes found thereon which are amplified or deleted, overexpressed or underexpressed in myeloma tumors to predict response to treatment, time-to-progression and survival upon treatment.
Thu, 27 Oct 2016 08:00:00 EDTA method is provided for characterising and/or prognosing prostate cancer in a subject comprising determining the expression level of at least one of CREM, ERRFI1, SRSF5, PDK4, HJURP, PDRG1, TRPM3, PDE4D, FI2, ADAMTS1, ADAMTS9, B3GNT5, CD38, CEBPD, CENPF, DKK1, EMP1, F3, IL1R1, IL8, JUNB, KLFIO, KLF4, LDLR, LGALS3, LPARI, MALAT1, MTUS1, MYBPC1, NFIL3, NR4A3, OAT, PI15, PTGS2, RHOBTB3, RIN2, RNFT2, SELE, SLC15A2, SOCS2, SOCS3, SSTR1, ST6GAL1, TSC22D1, XBP1 and ZFP36 in a sample from the subject. The method may be used to predict the likelihood of metastasis. Also disclosed are methods for diagnosing and selecting treatment for prostate cancer, together with corresponding methods of treatment. Systems, kits and computer programs for performing the methods are also provided.
Thu, 27 Oct 2016 08:00:00 EDTThe invention provides an in vitro method for determining the likelihood for a patient affected with a tumor to respond to a treatment with a pro-apoptotic peptide able to disrupt interaction between caspase 9 and PP2A, which method comprises determining expression level of at least each of VIM, MK167, TCF7L2, NEK2, BIRC5, MCL1, and PLK1 genes, in a biological sample of said patient.
Thu, 27 Oct 2016 08:00:00 EDTProvided herein, in certain embodiments, are biomarkers for use in predicting the clinical sensitivity of hematologic cancers, such as non-Hodgkin's lymphoma, and a patient's response to treatment with an immunomodulatory agent, such as 3-(4-an-rino-1-oxo-3-dihydro-isoindol-2-y])-piperidine-2,6-dione, which is also known as lenalidomide or Revlimid®. Also provided herein, in certain embodiments, are methods of treating or managing non-Hodgkin's lymphomas, including but not limited to diffuse large B-cell lymphoma (DLBCL), using prognostic factors.
Thu, 27 Oct 2016 08:00:00 EDTDisclosed are method and apparatus for identifying biomarkers and in particular for identifying biomarkers for use in making clinical assessments, such as early diagnostic, diagnostic, disease stage, disease severity, disease subtype, response to therapy or prognostic assessments. In one particular example, the techniques are applied to allow assessments of patients suffering from, suspected of suffering from, or with clinical signs of SIRS (Systemic Inflammatory Response Syndrome) being either infection-negative SIRS or infection-positive SIRS.
Thu, 27 Oct 2016 08:00:00 EDTModulators of intracellular chloride concentration for treating down syndrome The present invention relates to a modulator of a chloride transporter for use in the treatment of Down syndrome.
Thu, 27 Oct 2016 08:00:00 EDTA method is provided for inducing or enhancing an immune response in a mammal to a target polypeptide expressed in a plurality of cells of the mammal, which method comprises administering to the mammal an inhibitory nucleic acid which targets a region of a ribonucleic acid (RNA) which encodes said polypeptide. Also provided is a pharmaceutical composition comprising an inhibitory nucleic acid which targets a region of an RNA which encodes a target polypeptide expressed in a plurality of cells of a mammal, such that translation of an aberrant form of the target polypeptide occurs in said cells, said truncated form of the target polypeptide comprising one or more T cell epitopes; together with a pharmaceutically acceptable carrier or diluent.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention relates to a pharmaceutical composition and a method for regenerating normal tissue from fibrotic tissue, the pharmaceutical composition and the method employing a collagen-reducing substance. In accordance with the present invention, normal tissue can be therapeutically regenerated from fibrotic tissue.
Thu, 27 Oct 2016 08:00:00 EDTProvided is non-coded RNA of in-vivo infected microorganisms, parasitic microorganisms, symbiotic microorganisms and identification and application thereof. Also provided is a method of identifying the non-coded RNA of in-vivo pathogen sources.
Thu, 27 Oct 2016 08:00:00 EDTThe present disclosure relates to a compound which inhibits the binding of SLIT2 to ROBO or ROB02 or a compound which is an inhibitor of SLIT2, ROBO1 or ROB02 gene expression for use as an inhibitor of the neuronal remodeling in cancer.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention is directed to methods and compositions that provide therapy for at least one medical condition that directly or indirectly affects cardiac muscle cells (also known as cardiomyocytes) in a mammalian individual, including humans, dogs, cats, horse pigs, and so forth. The medical condition may be of any kind, including a cardiac condition such as heart failure, cardiomyopathy, myocardial infarction, and so forth. The medical condition may have a cardiac condition as its primary symptom or cause or it may be a secondary symptom or cause. The individual may be male or female and may be of any age.
Thu, 27 Oct 2016 08:00:00 EDTProvided herein are methods, compounds, and compositions for reducing expression of huntingtin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate Huntington's disease, or a symptom thereof.
Thu, 27 Oct 2016 08:00:00 EDTThe invention relates to dual targeting siRNA agents targeting a PCSK9 gene and a second gene, and methods of using dual targeting siRNA agents to inhibit expression of PCSK9 and to treat PCSK9 related disorders, e.g., hyperlipidemia.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention relates to the use of diesters of 2,5-dimethyl-2-hexenedioic acid, 2,5-dimethyl-3-hexenedioic acid and 2,5-dimethyladipic acid or a mixture thereof as a fragrance or as flavor, to a method for imparting or modifying a scent or a flavor to a composition by including said compounds into such composition, to a fragrance containing composition and/or a fragrance material containing said compounds and to a process for preparing diesters of 2,5-dimethyladipic acid.
Thu, 27 Oct 2016 08:00:00 EDTOrganopolysiloxane gel compositions containing an organopolysiloxane gel produced by hydrosilylation of an unsaturated silicone resin and a compound containing glycoside residues and a hydrosilylatable group with at least one Si—H-functional organopolysiloxane can form creamy, storage-stable gels which are capable of containing large amounts of polar or hydrophilic substances such as water and glycerol while remaining monophasic. The compositions are especially useful in providing cosmetic compositions with a silky skinfeel.
Thu, 27 Oct 2016 08:00:00 EDTThis invention relates pro-coagulant serpin molecules engineered by modification of the P4, P2, P1 and/or P1′ residues within the reactive center loop (RCL) to display increased specificity for anticoagulant proteases. These modified serpin molecules may be useful in therapy, for example as pro-coagulants for the treatment of bleeding.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention provides a novel compound useful in the treatment of hypoglycemia.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention provides a novel compound useful in the treatment of hypoglycemia.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention provides a novel compound useful in the treatment of hypoglycemia.
Thu, 27 Oct 2016 08:00:00 EDTWe describe an ELABELA polypeptide comprising a sequence CXXXRCXXXHSRVPFP (SEQ ID NO: 1), in which X signifies an amino acid residue, such as a sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 18, preferably CLQRRCMPLHSRVPFP (SEQ ID NO: 2), or a fragment, homoiogue, variant or derivative thereof which polypeptide is capable of maintaining self-renewal and/or pluripotency of a stem cell.
Thu, 27 Oct 2016 08:00:00 EDTA three-helix bundle protein, a polynucleotide encoding the three-helix bundle protein, a method of preparing the three-helix bundle protein, and a method of treating a cancer using the three-helix bundle protein.
Thu, 27 Oct 2016 08:00:00 EDTPolypeptides including Neurochondrin and autoantibodies binding to polypeptides including Neurochondrin are provided. Methods for diagnosing or treating diseases associated with neurological symptoms or cancers are also provided. The methods of diagnosis may include detecting an autoantibody binding to Neurochondrin in a sample from a patient. The methods of treatment may include administering a polypeptide comprising Neurochondrin to a patient.
Thu, 27 Oct 2016 08:00:00 EDTProvided are a new peptide, a vector inserting a DNA that codes said peptide, a transformant obtained by transformation with that vector, and applications of said peptide, vector and transformant. The peptide comprises an amino acid sequence set forth in SEQ ID NO: 1, or an amino acid sequence obtained by substituting, deleting or adding one or more amino acids to/from the amino acid sequence set forth in SEQ ID NO: 1. This peptide and the vector inserting a DNA that codes this peptide are suitable for use in an agent for promoting the proliferation of pancreatic hormone-producing cells, or a differentiation induction promoter that induces differentiation to pancreatic hormone-producing cells.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention relates, according to some embodiments, to variants of Semaphorin 3C (Sema3C) having amino acid modifications at furin-like pro-protein convertase cleavage sites, rendering these sites resistant to cleavage. The invention further provides, according to certain embodiments, compositions comprising the Sema3C variants, and methods of using the compositions for suppressing the growth of tumors and/or inhibiting the development of tumor metastases.
Thu, 27 Oct 2016 08:00:00 EDTThe present disclosure relates to protein and peptide chemistry. More particularly, it relates to compounds, compositions and uses thereof for promoting and inhibiting angiogenesis. The peptides of the present disclosure include peptides comprising SEQ ID NOs: 1-4 which promote angiogenesis and cell proliferation. Further, the anti-angiogenic compounds of the present disclosure include antisense oligonucleotides that hybridize or are complementary to the polynucleotides of SEQ ID NOs: 5-16, and the like.
Thu, 27 Oct 2016 08:00:00 EDTAn object to be solved by the present invention is to identify patients resistant to known HSP90 inhibitors, and to provide a novel therapeutic agent for treating the patients who have become resistant to known HSP90 inhibitors. As a means for solving the above problems, the present invention provides identification of the patients based on a protein, which is an HSP90 family protein having a mutation in the site corresponding to F138 of HSP90α class A consisting of the amino acid sequence of SEQ ID NO: 1, and use of a substance that inhibits the protein as an active ingredient of a therapeutic agent.
Thu, 27 Oct 2016 08:00:00 EDTThe invention relates to a polypeptide capable of binding human complement component 5 (C5), said polypeptide comprising the amino acid sequence (SEQ ID NO: 296)[BM]-[L2]-QSX42X43LLX46EAKKLX52X53X54Q wherein [BM] is a C5 binding motif; [L2] is an interconnecting loop; X42 is selected from A and S; X43 is selected from N and E; X46 is selected from A, S and C; X52 is selected from E, N and S; X53 is selected from D, E and S, provided that X53 is not D when X52 is N; and X54 is selected from A and S.
Thu, 27 Oct 2016 08:00:00 EDTThis invention refers to polynucleotides and non-hemorrhagic and non-immunogenic polypeptides of selective immunosuppressive activity on production of antibodies to antigens of different natures. The polypeptides described herein are useful for preparing pharmaceutical compositions for prevention or treatment of conditions that require immunosuppression, preferably, inflammatory, autoimmune, allergic and infectious diseases and rejection to transplanted organs.
Thu, 27 Oct 2016 08:00:00 EDTMethods of increasing the biological activity of toxins. Methods of increasing the biological activity of pesticide toxins through the incorporation of pro-regions into nucleic acid constructs for the production of said toxins.
Thu, 27 Oct 2016 08:00:00 EDTCompositions and methods for conferring pesticidal activity to bacteria, plants, plant cells, tissues and seeds are provided. Compositions comprising a coding sequence for a Bacillus thuringiensis toxin polypeptide are provided. The coding sequences can be used in DNA constructs or expression cassettes for transformation and expression in plants and bacteria. Compositions also comprise transformed bacteria, plants, plant cells, tissues, and seeds. In particular, isolated toxin nucleic acid molecules are provided. Additionally, amino acid sequences corresponding to the polynucleotides are encompassed, and antibodies specifically binding to those amino acid sequences. In particular, the present invention provides for isolated nucleic acid molecules comprising nucleotide sequences encoding the amino acid sequence shown in SEQ ID NO:5-26, or the nucleotide sequence set forth in SEQ ID NO: 1-4, as well as variants and fragments thereof.
Thu, 27 Oct 2016 08:00:00 EDTThe present disclosure relates to a class of engineered polypeptides having a binding affinity for albumin. In particular, the present invention relates to albumin binding polypeptides which have a high resistance to proteolytic cleavage and therapeutic use thereof. The disclosure provides an albumin binding polypeptide comprising an albumin binding motif, which motif consists of the amino acid sequence (SEQ ID NO. 1782)GXASDX5YKX8X9I X11X12AX14TVEGVX20 ALX23X24X25ILX28X29XB.
Thu, 27 Oct 2016 08:00:00 EDTThe invention provides a polypeptide chain capable of forming a polyhedron by self-assembly, nanostructure polyhedra self-assembled from single polypeptide chains and a process for preparing self-assembled polyhedra from polypeptide comprising coiled-coil-forming segments in defined combination that can form dimers that form the edges of the polypeptide polyhedra within a single polypeptide chain. A defined sequence of coiled-coil-forming segments allow self-assembly into a defined polyhedral nanostructure such as a polypeptide tetrahedron.
Thu, 27 Oct 2016 08:00:00 EDTThe presently disclosed subject matter relates to antagonists of PTEN and methods of using the same. In particular, the presently disclosed subject matter provides for PTEN antagonist peptides for use in treating central nervous system disorders. In an exemplary embodiment, the presently disclosed subject matter provides methods for promoting nerve fiber growth in a subject by administering to the subject a therapeutically effective amount of a PTEN antagonist peptide.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention provides peptide compounds that regulate the complement system and methods of using these compounds. The invention is an isolated, purified peptide of 30 amino acids derived from human astrovirus protein, called CP1. The invention is directed to peptide compounds that are peptide mimetics, peptide analogs and/or synthetic derivatives of CP1 having, for example, internal peptide deletions and substitutions, deletions and substitutions at the N-terminus and C-terminus, and that are able to regulate complement activation. The invention further provides pharmaceutical compositions of therapeutically effective amounts of the peptide compounds and a pharmaceutically acceptable carrier, diluent, or excipient for treating a disease or condition associated with complement-mediated tissue damage.
Thu, 27 Oct 2016 08:00:00 EDTDisclosed are peptide and peptidomimetic compounds generally according to formula (I) that are useful as GHRP analogs: R1-A1-A2-A3-A4-A5-R2 (I) wherein:A1 is Aib, Apc or Inp;A2 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp;A3 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp;A4 is 2Fua, Orn, 2Pal, 3Pal, 4Pal, Pff, Phe, Pim, Taz, 2Thi, 3Thi, Thr(Bzl);A5 is Apc, Dab, Dap, Lys, Orn, or deleted;R1 is hydrogen, (C1-6)alkyl, (C5-14)aryl, (C1-6)alkyl(C5-14)aryl, (C3-8)cycloakyl, or (C2-10)acyl; andR2 is OH or NH2;and pharmaceutical compositions and methods of use thereof.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention discloses a novel bile acid derivatives having substituted nitrogen functionality at C-11 and process for synthesis thereof. These C-11 substituted bile acid derivatives shows anticancer and antimycobacterial activity.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention relates to the compounds of the formulae (I) and (I-1) and the process for preparing the same, uses of the compounds for the treatment of diseases associated with platelet aggregation and in the manufacture of a medicament for the treatment of diseases associated with platelet aggregation, and relates to a pharmaceutical composition and a pharmaceutical formulation containing the compounds, wherein the definitions of R1, R2, R3 and R2a in the formulae are the same as those in the description.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention relates to fatty acid and fatty alcohol substituted nucleoside derivatives and nucleoside and nucleoside derivatives substituted on multivalent scaffolds (e.g., polymers, peptides, polycarboxylic acid substituted compounds, compounds containing polycycloSaligenyl groups) that display potent anti-HIV activity. Furthermore, they show enhanced activity against multi-drug resistant, R5, and cell-associated virus. Some of them also display activity against other sexually transmitted pathogens and sperm. The present invention provides their methods of synthesis, composition of matter, and methods of use. Emphasis is placed on their application as topical microbicides to treat or prevent sexual transmission of disease, especially HIV/AIDS.
Thu, 27 Oct 2016 08:00:00 EDTCompounds which allosterically modulate and/or inhibit factor XIa activity are provided, as are methods of their use. These compounds include i) sulfated gallolyl glucosides, ii) sulfated quinazolinones, and iii) sulfated inositol analogs. The compounds used as anticoagulant agents.
Thu, 27 Oct 2016 08:00:00 EDTDisclosed embodiments concern novel interleukin receptor associated kinases (IRAK) inhibitors and compositions comprising such inhibitors. Also disclosed are methods of making and using the compounds and compositions. The disclosed compounds and/or compositions may be used to treat or prevent an IRAK-associated disease or condition.
Thu, 27 Oct 2016 08:00:00 EDTThe invention relates generally to novel antibiotics and their analogs, to processes for the preparation of these novel antibiotics, to pharmaceutical compositions comprising the novel antibiotics; and to methods of using the novel antibiotics to treat or inhibit various disorders.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention relates to novel Pseudopolymorphs of Compound A, compositions comprising at least one Pseudopolymorph of Compound A, and methods of using the Pseudopolymorphs of Compound A for preparing compositions useful for treating or preventing HCV infection in a patient, wherein Compound A has the structure.
Thu, 27 Oct 2016 08:00:00 EDTThe present application relates to novel 6-substituted indazoles having a carboxamide side chain, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of endometriosis, lymphomas, macular degeneration, COPD and psoriasis.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention includes compounds having structural formula (I), or pharmaceutically acceptable salts, solvates, and/or esters thereof. These compounds are useful for treating itch or a pruritic condition. The present invention also includes compositions comprising the present compounds and methods of treating a pruritic condition. Furthermore, the present invention provides methods for preparing the compounds.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention provides imidazotriazinones as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
Thu, 27 Oct 2016 08:00:00 EDTThe present invention relates to tetrahydro-tetrazolo[1,5-a]pyrazine compounds of formula (I), wherein R1 denotes —R3, —CH2—R3 or —CO—R3; R2 denotes Ar2, Hetar2 or C3-7-cycloalkyl; and R3 denotes Ar3, Hetar3 or C3-7-cycloalkyl. These compounds are useful for inhibiting the retinoid-related orphan receptor γ (ROR γ, ROR-gamma) and for the prevention and/or treatment of medical conditions affected by ROR γ activity such as rheumatoid arthritis, multiple sclerosis, psoriasis, ulcerative colitis, asthma, autoimmune hepatitis or type 1 and type 2 diabetes.