Abstract: The present invention relates to recombinant C. difficile toxin A (TcdA) and toxin B (TcdB) and binary toxin A (CDTa) proteins comprising specifically defined mutations relative to the native toxin sequence that substantially reduce or eliminate toxicity. The invention also relates to vaccines and immunogenic compositions comprising these recombinant toxins, as well as combinations of these toxins with binary toxin B (CDTb), which are capable of providing protection against C. difficile infection and/or the effects thereof. The invention also relates to methods of inducing an immune response to C. difficile comprising administering the vaccines and immunogenic compositions described herein to a patient. The invention also encompasses methods of expressing recombinant C. difficile toxin A and toxin B and CDTa mutants and CDTb in recombinant expression systems.

Abstract: Described herein is the generation of optimized H3N2, H2N2 and B influenza HA polypeptides for eliciting a broadly reactive immune response to influenza virus isolates. The optimized HA polypeptides were developed through a series of HA protein alignments, and subsequent generation of consensus sequences, based on H3N2, H2N2 and B influenza isolates. Provided herein are optimized H3N2, H2N2 and B influenza HA polypeptides, and compositions, fusion proteins and VLPs comprising the HA polypeptides. Further provided are codon-optimized nucleic acid sequences encoding the HA polypeptides. Methods of eliciting an immune response against influenza virus in a subject are also provided by the present disclosure.

Abstract: The present invention provides novel PAR lderived cytoprotective oligopeptides or polypeptides which typically contain at least the first 4 N-terminal residues that are substantially identical to the corresponding N-terminal residues of Met1-Arg46 deleted human PAR 1 sequence. These cytoprotective oligopeptides or polypeptides are capable of activating PAR 1 and promoting PAR 1 cytoprotective signaling activities. The invention also provides engineered cells or transgenic non-human animals which harbor in their genome an altered PAR 1 gene that is resistant to cleavage at Arg41 and/or Arg46 residues. Additionally provided in the invention are methods of screening candidate compounds to identity additional cytoprotective compounds or cytoprotective proteases. The invention further provides therapeutic use or methods of employing a PAR 1 derived cytoprotective oligopeptide or polypeptide to treat conditions associated with tissue injuries or undesired apoptosis.

Abstract: The present invention relates to a Vibrio harveyi-specific binding Dscam of shrimps, a method for identification thereof and a use thereof. Primarily, Dscam cDNAs are prepared from V. harveyi-challenged shrimps. A database is established with various Dscam isoforms therein by means of numerous cloning and sequencing. After a phylogenetic analysis, a plurality of candidate Dscam isoforms is selected. Each recombinant protein of candidate Dscam isoforms is expressed through an expression system. Finally, the binding affinity between V. harveyi and each recombinant protein of candidate Dscam isoforms is measured to further selection of a V. harveyi-specific binding Dscam and the amino acid sequence thereof. Accordingly, the Dscam can be specifically binding to V. harveyi for eliminating or reducing V. harveyi.

Abstract: The biosynthesis of fungal bicyclo[2.2.2]diazaoctane indole alkaloids with a wide spectrum of biological activities have attracted increasing interest. Their intriguing mode of assembly has long been proposed to feature a non-ribosomal peptide synthetase, a presumed intramolecular Diels-Alderase, a variant number of prenyltransferases, and a series of oxidases responsible for the diverse tailoring modifications of their cyclodipeptide-based structural core. Until recently, the details of these biosynthetic pathways have remained largely unknown due to lack of information on the fungal derived biosynthetic gene clusters. Herein, we report a comparative analysis of four natural product metabolic systems of a select group of bicyclo[2.2.2]diazaoctane indole alkaloids including (+)/(?)-notoamide, paraherquamide and malbrancheamide, in which we propose an enzyme for each step in the biosynthetic pathway based on deep annotation and on-going biochemical studies.

Abstract: Compositions, methods, and kits are provided for treating CCR8 mediated diseases with applicability to atopic dermatitis and potential applicability to asthma, prurigo nodularis, nummular dermatitis, neurodermatitis, and lichen simplex chronicus and some lymphomas, multiple sclerosis, acquired immunodeficiency disease, peritoneal adhesions, Kaposi's sarcoma and atherogenesis—the expression of all of which, at least in part, is mediated by cells expressing the chemokine receptor CCR8. The compositions include proteins and fusion proteins from Molluscum contagiosum Virus (MCV) or variants, analogs and derivatives thereof which exhibit inhibitory activity. Examples of such MCV proteins are MC148 fusion protein (MC148fp) identified as MC148P-TAT-6xHis (“6xHis” disclosed as SEQ ID NO: 11), and its variants, fragments, analogs and derivatives which possess inhibitory activity.

Abstract: The present disclosure relates to Birt-Hogg-Dubé syndrome, nucleic acids encoding the BHD gene, and methods of using the nucleic acids and proteins encoded thereby. In particular, the present disclosure relates to methods of diagnosing BHD disease and related conditions, such as spontaneous pneumothorax and kidney cancer, and methods of treating BHD skin lesions.

Abstract: Reprogramming substances capable of substituting for Klf4, selected from the group consisting of members of the IRX family (e.g., IRX6), members of the GLIS family (e.g., GLIS1), members of the PTX family (e.g., PITX2), DMRTB1, and nucleic acids that encode the same, are provided. Also provided are a method of producing iPS cells, comprising the step of introducing into a somatic cell both one or more kinds of the above-described nuclear reprogramming substances and a substance capable of inducing iPS cells from a somatic cell when combined with Klf4. Still also provided are iPS cells comprising an extraneous nucleic acid that encodes any one of the above-described nuclear reprogramming substances, that can be obtained by the method, and a method of producing somatic cells by inducing the iPS cells to differentiate.

Abstract: The invention provides seed and plants of tomato line PSQ 24-2147. The invention thus relates to the plants, seeds and tissue cultures of tomato line PSQ 24-2147, and to methods for producing a tomato plant produced by crossing such plants with themselves or with another tomato plant, such as a plant of another genotype. The invention further relates to seeds and plants produced by such crossing. The invention further relates to parts of such plants, including the fruit and gametes of such plants.

Abstract: The invention relates to novel designer osteogenic proteins having altered affinity for a cognate receptor, nucleic acids encoding the same, and methods of use therefor. More preferably, the novel designer osteogenic proteins are designer BMPs and have altered affinity for a cognate BMP receptor. The designer BMPs demonstrate altered biological characteristics and provide potential useful novel therapeutics.

Abstract: The invention disclosed herein relates to methods and materials for producing simvastatin and related compounds such as huvastatin.

Abstract: The invention provides seed and plants of tomato line CHI 18-2101. The invention thus relates to the plants, seeds and tissue cultures of such plants, and to methods for producing a tomato plant produced by crossing such plants with themselves or with another tomato plant, such as a plant of another genotype. The invention further relates to seeds and plants produced by such crossing. The invention further relates to parts of such plants, including the fruit and gametes of such plants.

Abstract: Methods and compositions for delivering polynucleotides are provided. One embodiment provides a non-viral vector comprising a recombinant polynucleotide-binding protein comprising a protein transduction domain operably linked to a targeting signal.

Abstract: A method for cultivating a bacterial cell comprising the addition of an amino acid in an alkaline solution used for pH regulation. Also an aspect is a method for producing a polypeptide comprising the steps of a) providing a bacterial cell comprising a nucleic acid encoding the polypeptide, b) cultivating the provided cell, c) adjusting the pH value during the cultivating with a basic solution comprising an amino acid, d) recovering the polypeptide from the cell or the cultivation medium and thereby producing the polypeptide.

Abstract: The invention provides seed and plants of tomato line PSQ-9Z08005. The invention thus relates to the plants, seeds and tissue cultures of tomato line PSQ-9Z08005, and to methods for producing a tomato plant produced by crossing such plants with themselves or with another tomato plant, such as a plant of another genotype. The invention further relates to seeds and plants produced by such crossing. The invention further relates to parts of such plants, including the fruit and gametes of such plants.

Abstract: Methods and compositions involving polypeptides having an aglycosylated antibody Fc domain. In certain embodiments, polypeptides have an aglycosylated Fc domain that contains one or more substitutions compared to a native Fc domain. Additionally, some embodiments involve an Fc domain that is binds some Fc receptors but not others. For example, polypeptides are provided with an aglycosylated Fc domain that selectively binds Fc?RIIa, but that is significantly reduced for binding to the highly homologous Fc?RIIb receptors. Furthermore, methods and compositions are provided for promoting antibody-dependent cell-mediated toxicity (ADCC) using a polypeptide having a modified aglycosylated Fc domain and a second non-Fc binding domain, which can be an antigen binding region of an antibody or a non-antigen binding region. Some embodiments concern antibodies with such polypeptides, which may have the same or different non-Fc binding domain.

Abstract: The invention relates to therapeutic vaccines for the treatment of neoplasias caused by the human papillomavirus (HPV). In particular, the vaccines of the present invention are formed by chimeric virus-like capsids of birnavirus containing papillomavirus antigens.

Abstract: The present disclosure relates to chimeric polypeptide having TGF-beta activity, nucleic acids encoding the polypeptides, and host cells for producing the polypeptides.

Abstract: Polypeptides with xylanase activity modified to increase bran solubilization and/or xylanase activity. The modification comprises at least an amino acid modification i position 110 and may have further modifications of one or more amino acids in position 11, 12, 13, 34, 54, 77, 81, 99, 104, 113, 114, 118, 122, 141, 154, 159, 162, 164, 166 or 175 wherein the positions are determined as the position corresponding the position of Bacillus subtilis xylanase (SEQ ID NO 1) The polypeptides have at least 88% identity with SEQ ID NO 1 or 75% identity to a sequence selected from SEQ ID NO 2-22.

Abstract: The invention provides isolated nucleic acid encoding one or more gene products that allow for degradation of caffeine and related structures, and for preparation of intermediates in that catabolic pathway. Further provided are methods of using one or more of those gene products.

Abstract: The invention provide isolated arrestin domain-containing protein 1 (ARRDC1)-mediated micro vesicles (ARMMs). Methods for generating and for isolating ARMMs are also provided herein. ARMMs can be used to deliver agents, for example, nucleic acids (e.g., siRNAs, microRNAs, lincRNAs), proteins (e.g., transcription factors, chromatin modulators, kinases, phosphorylases, or recombinases), or small molecules to target cells in vitro and in vivo, and methods for such ARMM-mediated delivery are provided herein. Diagnostic and therapeutic methods using ARMMs are also described herein.

Abstract: The present invention relates to polypeptides and more particularly to Transcription Activator-Like Effector derived proteins that allow to efficiently target and/or process nucleic acids. Particularly, the present invention reports the characterization of TALE derived proteins that can efficiently target methylated DNA. The present invention more specifically relates to TALE derived proteins that allow activation of methylated promoters responsible for gene silencing.

Abstract: The presently-disclosed subject matter includes fluorescent protein-based indicators for detecting ions, small molecule analytes, or combinations thereof. In some embodiments the indicators include a polypeptide, which itself includes a fluorescent polypeptide, a compound-binding polypeptide, and a polypeptide target of the compound-binding polypeptide. In some embodiments the polypeptide includes an EosFP polypeptide, a calmodulin polypeptide, and a M13 polypeptide, or fragments and/or variants thereof. The presently-disclosed subject matter also includes methods for detecting calcium in a sample with embodiments of the present polypeptides. In some embodiments the present indicators experience a permanent shift from green to red fluorescent when exposed to an detecting substance, such as calcium.

Abstract: Baboon Adenovirus (BaAdV)-2/4 and BaAdV-3 are disclosed herein. BaAdV-2/4 and BaAdV-3 polynucleotide, polypeptides and antibodies that specifically bind BaAdV-2/4 and/or BaAdV-3 are disclosed. Methods are disclosed for detecting BaAdV-2/4 and BaAdV-3. Methods are also disclosed for treating, preventing, and inducing an immune response to BaAdV-2/4 and/or BaAdV-3. Kits are also provided.

Abstract: The invention provides methods, compositions, and kits featuring novel RIG-I like receptor activators or inhibitors for use in preventing or treating virus infection or autoimmune disease.

Abstract: Methods of treating a food allergy, allergic reactions, hypersensitivity, inflammatory responses, inflammation are provided. In one method, histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) is contacted with a compound that inhibits or reduces binding of HRF/TCTP to an immunoglobulin in order to treat the food allergy, allergic reaction, hypersensitivity, inflammatory response, or inflammation. Methods of reducing or decreasing the probability, severity, frequency, duration or preventing a subject from having an acute or chronic food allergy, allergic reaction, hypersensitivity, an inflammatory response or inflammation, are also provided.

Abstract: The present invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum wherein (i) the protein binds specifically to nerve cells with a higher or lower affinity as the native neurotoxin; (ii) the protein has an increased or reduced neurotoxicity compared to the native neurotoxin, the neurotoxicity being preferably determined in the hemidiaphragm assay; and/or (iii) the protein comprises a lower affinity against neutralizing antibodies compared to the native neurotoxin. The invention also relates to methods for producing the same and the use thereof in cosmetic and pharmaceutical compositions.

Abstract: The invention relates to standards for quantifying pathogenic aggregates or oligomers of endogenous proteins which characterize a protein aggregation disease, amyloid degeneration or protein misfolding diseases and use of these standards for quantifying these pathogenic aggregates or oligomers.

Abstract: The present invention relates to extended recombinant polypeptide (XTEN) compositions, conjugate compositions comprising XTEN and XTEN linked to cross-linkers useful for conjugation to pharmacologically active payloads, methods of making highly purified XTEN, methods of making XTEN-linker and XTEN-payload conjugates, and methods of using the XTEN-cross-linker and XTEN-payload compositions.

Abstract: A urinary biomarker for urinary tract cancers and applications of the same are revealed. TACSTD2 is used as a non-invasive urinary biomarker for urinary tract cancers due to a feature that the TACSTD2 protein is increased significantly in urine of patients with urinary tract cancers. The quantitative urinary biomarker shows high specificity and high sensitivity for urinary tract cancer detection. Besides increasing screening efficiency, early diagnosis and early treatment of urinary tract cancers, the biomarker can also be used to assess malignancy of urinary tract cancers and monitor tumor progression for determining optimal treatment against the disease and improving the treatment results.

Abstract: Provided is a porcine CD28 receptor molecule, which is: 1) a protein consisting of an amino acid sequence represented by SEQ ID NO:2, or 2) a protein derived from 1) by substitution, deletion or addition of one or several amino acids in the amino acid sequence represented by SEQ ID NO:2 and having equivalent activity with 1). Further provided is a gene for coding the porcine CD28 receptor, the nucleotide sequence of which is shown as SEQ ID NO:1. When the provided co-stimulating receptor CD28 is expressed specifically and highly in a T cell, the activation, proliferation and cell factor secretion activity of the T cell when stimulated by an antigen can be enhanced, thereby enhancing the acquired immune response of a host and enhancing the immune effect of a vaccine. FIG. 8 is selected as the drawing attached to the Abstract.

Abstract: This disclosure relates to novel peptide agents, e.g., antibodies and antigen-binding fragments thereof, that bind hemagglutinin protein of influenza viruses, and methods of their use.

Abstract: The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor and inhibits tumor growth. The present invention further provides a method of treating cancer, the method comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor protein and inhibits tumor growth.

Abstract: With the aim of providing a liposome, having a hydrophilic polymer introduced into the outer surface of the liposome membrane, which is a liposome capable of allowing the liposome-entrapped substance to escape from the endosome and be released into the cytoplasm, a liposome membrane component bound to the peptide shown by (a) or (b) below and a liposome membrane component bound to one end of a hydrophilic polymer the other end of which is bound to the peptide shown by (a) or (b) below are included in the liposome: (a) a peptide comprising the amino acid sequence of SEQ ID NO:1; (b) a peptide comprising the amino acid sequence of SEQ ID NO:1 with 1 or more amino acids deleted, replaced or added therein, and capable of fusing lipid membranes with one another under acidic conditions.

Abstract: The invention provides hypoallergenic variants of Bet v 1 major allergen from Betula verrucosa plant pollen and the use thereof for the preventive or therapeutic treatment of allergic diseases.

Abstract: Embodiments herein include methods and constructs that can be used to co-express two or more polypeptides of interest from a single polynucleotide encoding a precursor polypeptide. Within this precursor polypeptide can reside at least one autonomous processing unit, which can mediate release of flanking polypeptides of interest in cis. The processing unit can include an N-terminal autocatalytic cleavage domain and a C-terminal cleavage domain. Some embodiments include constructs and methods for co-expressing polypeptides without N- or C-terminal overhangs, in any cellular or extracellular location, and/or in stoichiometric ratios.

Abstract: An objective of the present invention is to provide chimeric receptors containing a mouse Fc? receptor extracellular domain and a human Fc? receptor transmembrane domain, or chimeric receptors containing a mouse Fc? receptor extracellular domain and a human ? chain transmembrane domain. Another objective of the present invention is to provide methods for measuring the ADCC activity of mouse antibodies and methods of screening for mouse antibodies having ADCC activity, using the chimeric receptors. To accomplish the above-mentioned objectives, the present inventors produced chimeric molecules by fusing the extracellular domain of mouse Fc?R3 or mouse Fc?R4 with the transmembrane domain/intracellular domain of human ? chain or human Fc?R3, and expressed the chimeric molecules in human NK92 cells.

Abstract: The invention relates to materials and methods of conjugating a water soluble fatty acid derivative to a therapeutic protein comprising contacting the therapeutic protein with an activated water soluble fatty acid derivative under conditions that allow conjugation.

Abstract: The present invention relates to compositions comprising Haemophilus influenzae Protein E and Pilin A. More particularly, the present application relates to fusion proteins and immunogenic compositions comprising Protein E and PilA, vaccines comprising such immunogenic compositions and therapeutic uses of the same.

Abstract: The methods and compositions described herein are based, in part, on the discovery of a polypeptide of soluble CD23 (sCD23) that binds and sequesters IgE. Thus, the sCD23 peptides, polypeptides and derivatives described herein are useful for treating conditions or disorders involving increased IgE levels such as e.g., allergy, anaphylaxis, inflammation, lymphoma, and certain cancers.

Abstract: The present invention provides antigens and vaccines useful in prevention of infection by Yersinia pestis. The present invention provides pharmaceutical compositions of such antigens and/or vaccines. The present invention provides methods for the production of Y. pestis protein antigens in plants, as well as methods for their use in the treatment and/or prevention of Y. pestis infection.

Abstract: The invention relates to novel polypeptides and cells comprising the polypeptides. The polypeptides and cells are used in methods to identify and/or isolate cells producing a protein with specific biological functions. In particular, the methods may be used for identifying, selecting, and isolating cells producing antigen-specific monoclonal antibodies.

Abstract: The invention provides seed and plants of tomato line FDS 15-2118. The invention thus relates to the plants, seeds and tissue cultures of tomato line FDS 15-2118, and to methods for producing a tomato plant produced by crossing such plants with themselves or with another tomato plant, such as a plant of another genotype. The invention further relates to seeds and plants produced by such crossing. The invention further relates to parts of such plants, including the fruit and gametes of such plants.

Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acid vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Abstract: The invention relates to the use of the ubiquitous vertebrate glucose transporter GLUT1, or of fragments or sequences derived thereof, for the in vitro diagnosis of cancers, when used as a tumor marker, or for the screening of compounds useful for the preparation of drugs for the prevention or the treatment of pathologies linked to an infection of an individual with a PTLV, or pathologies linked to an overexpression of GLUT1 on cell surfaces, or the in vitro detection of GLUT1 on cell surfaces. The invention also relates to pharmaceutical compositions containing GLUT1, or fragments or sequences derived thereof, and to their uses such as in the frame of the prevention or the treatment of pathologies linked to an infection of an individual with a PTLV.

Abstract: This application relates to Group B Streptococcus (“GBS”) vaccines comprising combinations of GBS polypeptide antigens where the polypeptides contribute to the immunological response in a recipient. Preferably, the compositions of the invention comprise a combination of two or more GBS antigens, wherein said combination includes GBS 80 or a fragment thereof. In one embodiment, the combination may consist of two to thirteen GBS antigens selected from an antigen group consisting of GBS 80, GBS 91, GBS 104, GBS 184, GBS 276, GBS 305, GBS 322, GBS 330, GBS 338, GBS 361, GBS 404, GBS 690, and GBS 691.

Abstract: The present invention concerns methods and compositions for treating or preventing a bacterial infection, particularly infection by a Staphylococcus bacterium. The invention provides methods and compositions for stimulating an immune response against the bacteria. In certain embodiments, the methods and compositions involve an Ebh antigen.

Abstract: Disclosed are DNA polymerases having increased reverse transcriptase efficiency relative to a corresponding, unmodified polymerase. The polymerases are useful in a variety of disclosed primer extension methods. Also disclosed are related compositions, including recombinant nucleic acids, vectors, and host cells, which are useful, e.g., for production of the DNA polymerases.

Abstract: Disclosed herein are methods and compositions for modulating the expression of a HLA locus or for selectively deleting or manipulating a HLA locus or HLA regulator.

Abstract: In some embodiments, the present invention provides respiratory syncytial virus (RSV) F proteins, polypeptides and protein complexes that comprise one or more cross-links to stabilize the protein, polypeptide or protein complex in its pre-fusion conformation. In some embodiments the present invention provides RSV F proteins, polypeptides and protein complexes comprising one or more mutations to facilitate such cross-linking. In some embodiments the present invention provides compositions comprising such proteins, polypeptides or protein complexes, including vaccine compositions, and methods of making and using the same.