Abstract: The present invention provides a method for assessing embryotoxicity of a chemical comprising: (1) a first step of measuring the expression level of one or more genes selected from among genes each comprising any of the nucleotide sequences of SEQ ID NOs: 1 to 78 and 101 to 230 and orthologous genes thereof in a sample from a non-human mammal or mammalian cell which has come into contact with a test chemical; and (2) a second step of comparing the measured value of the expression level of the gene in the sample obtained in the first step with a control value of the expression level of the gene and based on the difference assessing the level of the embryotoxicity of the test chemical in the sample; and so on.

Abstract: Modified factors VII/VIIa with a high stability, nucleic acids encoding such modified factors VII/VIIa, and methods of preparing the same.

Abstract: The present invention refers to single-chain fusion proteins comprising three soluble TNF superfamily (TNFSF) cytokine domains and nucleic acid molecules encoding these fusion proteins. The fusion proteins are substantially non-aggregating and suitable for therapeutic, diagnostic and/or research applications.

Abstract: Methods and compositions are presented for the administration of transposon-based vectors to an animal or human to provide gene therapy to the animal or human

Abstract: Heterodimeric meganuclease comprising two domains of different meganucleases which are in two separate polypeptides, said heterodimeric meganuclease being able to cleave a chimeric DNA target sequence comprising one different half of each parent meganuclease DNA target sequence. Use of said herodimeric meganuclease and derived products for genetic engineering, genome therapy and antiviral therapy.

Abstract: A transgenic animal model for evaluating growth, survival and/or metastasis of xenotransplanted normal or tumor cells or tissue is disclosed, in which a human growth factor, hHGF stimulates growth in vivo of human cells or tissue. A strain of Tg mice on the C3H background that is immunocompromised as a result of a homozygous scid gene has been bred which express a nucleic acid encoding hHGF/SE The ectopically expressed hHGF/SF ligand significantly enhances growth of human tumor cell lines and explanted tumor cells or tissue that express the Met receptor for hHGF. Such animals also have an enlarged normal livers and greater than normal liver regenerative capacity. Any Met-expressing hHGF-dependent human cells, including hepatocytes and various stem cells can survive and grow in such animals.

Abstract: The present invention relates to a method of generating an induced pluripotent stem (iPS) cell comprising the step of introducing into a target cell one or two coding sequences each giving rise upon transcription to a factor that contributes to the reprogramming of said target cell into an induced pluripotent stem cell and selected from Oct3/4 or a factor belonging to the Myc, Klf and Sox families of factors, wherein the target cell endogenously expresses at least the factors that are not encoded by the coding sequences to be introduced and selected from Oct3/4 or factors belonging to the Myc, Klf and Sox families of factors, and wherein the cell resulting from the introduction of the one or two coding sequences expresses the combination of factor Oct3/4 and at least one factor of each family of factors selected from the group of Myc, Klf and Sox.

Abstract: The present invention relates to isolated polypeptides having phytase activity and isolated polynucleotides encoding the polypeptides. The polypeptides are related to a phytase derived from Hafnia alvei, the amino acid sequence of which is shown in the appended sequence listing as SEQ ID NO: 10. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides, in particular within animal feed.

Abstract: The present invention relates to methods and compositions for high content drug screening in C. elegans which may be used to identify compounds that treat disorders associated with protein aggregation.

Abstract: Factor IX variants are described with an increase in the number of glycosylation sites. The Factor IX variants have an increased half life and/or recovery.

Abstract: The present invention relates to genetically encoded calcium sensors comprising fluorescent proteins and troponin C as calcium-binding moiety. More specifically, the invention provides a polypeptide comprising a donor moiety for fluorescence resonance energy transfer (FRET), at least two calcium binding moieties derived from the C-terminal domain of troponin C, and an acceptor moiety for FRET. Also, the invention provides nucleic acid molecules, expression vectors, host cells, and transgenic animals. In addition, methods for detecting a change in Ca2+ concentration or Mg2+ concentration, as well as uses of the polypeptides for preparing diagnostic compositions for the detection of changes in the Ca2+-concentration or Mg2+-concentration are provided.

Abstract: The present invention relates to various in vitro methods of diagnosing a vasoregulation disorder or a predisposition thereto in a subject being suspected of having developed or of having a predisposition to develop a vasoregulation disorder or in a subject being suspected of being a carrier for a vasoregulation disorder, wherein the vasoregulation disorder is selected from hypertension, migraine, pre-eclampsia and recurrent pregnancy loss. Moreover, the present invention also relates to methods for identifying compounds capable of modulating coagulation factor XII activity, suitable as medicaments or as lead compound for a medicament for the treatment and/or prevention of a vasoregulation disorder. Furthermore, the present invention relates to gene therapy methods and to a kit for diagnosing a vasoregulation disorder.

Abstract: The invention provides peptides and the nucleic acid sequences that encode them. The invention further provides therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of apoptosis associated disorders.

Abstract: A modified arthropod, an arthropod-modifying bacterium, and use thereof as an agent for control of diseases transmitted by arthropods, particularly mosquitoes, is provided. More specifically, an isolated arthropod-adapted Wolbachia bacterium capable of modifying one or more biological properties of a mosquito host is provided. The modified arthropod may be characterized as having a shortened life-span, a reduced ability to transmit disease, a reduced susceptibility to a pathogen, a reduced fecundity, and/or a reduced ability to feed from a host, when compared to a corresponding wild-type arthropod.

Abstract: Materials and Methods related to gene targeting (e.g., gene targeting with transcription activator-like effector nucleases; “TALENS”) are provided.

Abstract: The present invention relates to a polynucleotide from Emiliana huxleyi which codes for a desaturase and which can be employed for the recombinant production of polyunsaturated fatty acids. The invention furthermore relates to vectors, host cells and transgenic nonhuman organisms which comprise the polynucleotide according to the invention, and to the polypeptides encoded by the polynucleotide. The invention furthermore relates to antibodies against the polypeptide according to the invention. Finally, the invention also relates to production methods for the polyunsaturated fatty acids and for oil, lipid and fatty acid compositions and to their use as drugs, cosmetics, foodstuffs, feedstuffs, preferably fish food, or food supplements.

Abstract: The invention provides transgene constructs for expressing chimeric antibodies, and transgenic non-human host animals carrying such constructs, wherein the chimeric antibodies comprise human variable regions and constant regions of the non-human transgenic host animal. The presence of immunoglobulin constant regions of the host animal allows for generation of improved antibodies in such transgenic host animals. Subsequently, the chimeric antibodies can be readily converted to fully human antibodies using recombinant DNA techniques. Thus, the invention provides compositions and methods for generating human antibodies in which chimeric antibodies raised in vivo in transgenic mice are used as intermediates and then converted to fully human antibodies in vitro.

Abstract: Demethylation of a methylated DNA sequence in a eukaryotic cell is described, utilising a molecule that includes at least a first domain that exhibits a cytidine deaminase activity and at least a second domain that confers either a specific or non-specific DNA binding activity. The molecules of the invention are useful in somatic cell nuclear transfer and also in cancer therapy.

Abstract: The present invention relates to a novel promoter and its use in driving expression of foreign genes in transgenic animals (especially pigs). Accordingly, the present invention provides a method for producing transgenic animals harboring heterologous genes regulated by the promoter of the present invention.

Abstract: Nucleic acid compositions encoding non-aggregating chromo/fluoroproteins and mutants thereof, as well as the proteins encoded by the same, are provided. The proteins of interest are polypeptides that are non-aggregating colored and/or fluorescent proteins, where the non-aggregating feature arises from the modulation of residues in the N-terminus of the protein and the chromo and/or fluorescent feature arises from the interaction of two or more residues of the protein. Also provided are fragments of the subject nucleic acids and the peptides encoded thereby, as well as antibodies to the subject proteins and transgenic cells and organisms. The subject protein and nucleic acid compositions find use in a variety of different applications. Finally, kits for use in such applications, e.g., that include the subject nucleic acid compositions, are provided.

Abstract: The present invention relates to a polymorphic CYP2C8-polynucleotide. Moreover, the invention relates to genes or vectors comprising the polynucleotides of the invention and to a host cell genetically engineered with the polynucleotide or gene of the invention. Further, the invention relates to methods for producing molecular variant polypeptides or fragments thereof, methods for producing cells capable of expressing a molecular variant polypeptide and to a polypeptide or fragment thereof encoded by the polynucleotide or the gene of the invention or which is obtainable by the method or from the cells produced by the method of the invention. Furthermore, the invention relates to an antibody which binds specifically the polypeptide of the invention. Moreover, the invention relates to a transgenic non-human animal. The invention also relates to a solid support comprising one or a plurality of the above mentioned polynucleotides, genes, vectors, polypeptides, antibodies or host cells.

Abstract: Methods and kits for the diagnosis of illnesses related to protocadherin 19 (PCDH 19) protein deficiency or altered PCDH 19 protein function, in particular EFMR (Epilepsy and Mental Retardation limited to Females) are provided, as well as methods and kits for the identification of a predisposition to such illnesses and methods of screening subjects to identify carriers of such illnesses and methods and kits for the therapeutic or prophylactic treatment of PCDH 19 deficiency or altered PCDH 19 protein function. Further, nucleotide and amino acid sequences corresponding to a complete PCDH19 open reading frame (ORF), mutant sequences encoding non-functional PCDH19 mRNA or altered PCDH19 mRN A are described along with transformed cells and non-human transgenic animals comprising wild-type or mutant PCDH19 ORF nucleotide sequences.

Abstract: The invention provides compositions including modified blood clotting factors that have a non-native proteolytic cleavage site engineered into them allowing intracellular cleavage and secretion of an active form. The compositions are useful in the methods for treating a bleeding or clotting disorder.

Abstract: The present invention relates to a transgenic animal, which comprises in its genome a recombinant polynucleotide encoding one or more reporter proteins and a monocyte chemotactic protein-1 (MCP-1) promoter, wherein the one or more reporter proteins are expressed under the control of the MCP-1 promoter. A method for monitoring endogenous expression of MCP-1 in vivo is also provided, which is useful for identifying a regulator of the expression of MCP-1 or an anti-inflammatory agent.

Abstract: The present invention relates to the identification of proteins located on the cell surface of dendritic cells or precursors thereof, particularly antigen presenting dendritic cells. In particular, the present invention relates to compounds such as antibodies that bind these proteins. These compounds can be used to detect and/or enrich a subset of dendritic cells or precursors thereof. These compounds can also be used to target antigens to dendritic cells or precursors thereof to modulate a humoral and/or T cell mediated immune response to an antigen, or used to target cytotoxic agents to dendritic cells or precursors thereof involved in diseased states.

Abstract: The present invention relates to an in vitro method of detecting secretory granules (SGs) of different ages in a cell by differentially labelling said SGs according to their age comprising (a) contacting a cell capable of forming SGs and expressing 1. a (poly)peptide specific for SGs, wherein said (poly)peptide has a binding site common for at least three different substances A, B and C covalently binding thereto or 2.

Abstract: The present invention relates to the use of regulatory sequences for mediating specific, early transient expression in proliferative neuronal determined cells. Furthermore, the uses of recombinant nucleic acid molecules comprising said defined regulatory sequences for mediating specific, early transient expression in proliferative neuronal determined cells as well as for the generation of non-human transgenic organisms and/or host cells are disclosed. In addition, the invention provides for transgenic non-human animals and/or host cells comprising said regulatory sequences and/or recombinant nucleic acid molecules. The invention also describes methods for the preparation of such vectors, host cells and transgenic non-human animals as well as methods for the detection and/or isolation of neuronal determined cells.

Abstract: The present invention relates to a novel mite composition comprising a population of a phytoseiid predatory mite species and a factitious host population, which may be employed for rearing said phytoseiid predatory mite species or for releasing the pyrltoseiid predatory mite species in a crop. According to further aspects the invention relates to a method for rearing a phytoseiid predatory mite species, to the use of the mite composition and to a method for biological pest control in a crop, which employ the mite composition.

Abstract: The invention relates to the storage of information in nucleic acid sequences. The invention also relates to nucleic acid sequences containing desired information and to the design, production or use of sequences of this type.

Abstract: The invention provides methods and compositions for generating non-human transgenic cells and organisms that are transgenic at one or more gene sequences by separately recombining fragments of a complete gene in temporal sequence. According to the methods of the invention, a set of DNA constructs containing a non-endogenous DNA sequence flanked and/or operably linked at its ends by sequences from the non-human organism are generated by recombination in a bacterial cell, for example, in E. coli. The DNA constructs that are produced can then be introduced into a non-human homologous recombination competent cell where successive cells will contain recombined segments of a target gene, with the ultimate cell in a line containing an endogenous target gene completely replaced by genomic DNA of another species.

Abstract: The invention relates to a method for screening for the effects of non-genotoxic carcinogens in an animal model. The invention also relates to animal models that are suitable for use in such a method, and cell lines derived from these animals for in vitro screening purposes. More specifically, the invention relates to a transgenic rodent animal which has been humanised for the nuclear transcription factors CAR, PXR and PPAR?, and in which the endogenous equivalent genes have been rendered inoperable.

Abstract: The present invention provides a method for enhanced production of a gene product of interest in a cell, using the AAV replication machinery. The present invention further relates to a cell for use in the method of the invention and a non-human transgenic animal or a transgenic plant comprising a cell of the invention.

Abstract: Monoclonal antibodies against gonadotropin releasing hormone (GnRH) receptor induce cellular apoptosis of various cancer cells expressing this surface receptor. The monoclonal antibodies and their humanized forms, or fragments thereof, can serve as anti-cancer agents for the treatment of cancer in humans, and can function as analogs of GnRH to affect regulation of reproductive functions or fertility in humans.

Abstract: The present invention relates to serine hydroxymethyltransferase (E.C. 2.1.2.1) as novel target for herbicides, and to nucleic acid sequences encoding a polypeptide with the biological activity of a serine hydroxymethyltransferase, which, when not present, bring about growth retardation symptoms and chlorotic leaves, comprising the nucleic acid sequence SEQ ID No:3, and functional equivalents of the abovementioned nucleic acid sequence or the nucleic acid sequence SEQ ID NO:7 and functional equivalents of the abovementioned nucleic acid sequence. Moreover, the present invention relates to the use of the abovementioned nucleic acid sequences, of functional analogs of the SEQ ID NO:3 or SEQ ID NO:7 or of polypeptides encoded by one of the abovementioned nucleic acid sequences in a method for identifying herbicidally active compounds which inhibit serine hydroxymethyltransferases, and to the use of these compounds which have been identified by the method as herbicides.

Abstract: This invention relates to novel protein transduction domains (PTDs) derived from secretory leukocyte protease inhibitor (SLPI). SLPI-derived PTDs are able to deliver cargo moieties in vivo and in vitro into the cytoplasm and nucleus of a host cell. The invention also relates to a transduction complex comprising one or more SLPI-derived PTDs linked or fused to one or more cargo moieties, which may comprise, for example, proteins, nucleic acids, lipids, carbohydrates, small molecules and other chemical compounds. The invention also relates to the manufacture of SLPI-derived PTDs, complexes comprising them; compositions comprising SLPI-derived PTDs or complexes; and utilization of SLPI-derived PTDs or complexes comprising them for therapeutic, diagnostic and research methods involving delivery of heterologous molecules across cellular membranes, and especially, across nuclear membranes.

Abstract: The invention relates to poly(ADP-ribose)polymerase (PARP) homologs which have an amino acid sequence which has a) a functional NAD binding domain and b) no zinc finger sequence motif of the general formula CX2CXmHX2C in which m is an integral value from 28 or 30, and the X radicals are, independently of one another, any amino acid; and the functional equivalents thereof; nucleic acids coding therefor; antibodies with specificity for the novel protein; pharmaceutical and gene therapy compositions which comprise products according to the invention; methods for the analytical determination of the proteins and nucleic acids according to the invention; methods for identifying effectors or binding partners of the proteins according to the invention; novel PARP effectors; and methods for determining the activity of such effectors.

Abstract: The present invention relates, in general, to a method for introducing a heterologous replacement gene sequence into a host embryonic stem cell to replace an endogenous host gene target sequence. In particular, the invention relates to a method for inserting large pieces of DNA into embryonic stem cells with improved efficiency, by first deleting the endogenous host gene target sequence, and subsequently utilising two proximally positioned site-specific recombinase target (RT) sites to insert a heterologous replacement gene sequence into the host chromosome.

Abstract: The invention relates to a novel antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor both in a ligand-dependent and in a ligand-independent manner, with an improved antagonistic activity, said antibody comprising a modified hinge region. The invention also relates to a composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer.

Abstract: The invention provides, inter alia, methods for treating cancer, compositions for treating cancer, and methods and compositions for diagnosing and/or detecting cancer. In particular, the present invention provides compositions and methods for treating, diagnosing and detecting cancers associated with AMIGO-2 overexpression.

Abstract: The present invention provides a new fluorescent protein, engineered to facilitate release from self-cleaving peptides.

Abstract: Isolated human monoclonal antibodies which bind to human CD38, and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO226, PRO257, PRO268, PRO290, PRO36006, PRO363, PRO365, PRO382, PRO444, PRO705, PRO1071, PRO1125, PRO1134, PRO1155, PRO1281, PRO1343, PRO1379, PRO1380, PRO1387, PRO1419, PRO1433, PRO1474, PRO1550, PRO1571, PRO1572, PRO1759, PRO1904, PRO35193, PRO4341, PRO4348, PRO4369, PRO4381, PRO4407, PRO4425, PRO4985, PRO4989, PRO5737, PRO5800, PRO5993, PRO6017, PRO7174, PRO9744, PRO9821, PRO9852, PRO9873, PRO10196, PRO34778, PRO20233, PRO21956, PRO57290, PRO38465, PRO38683 or PRO85161 genes.

Abstract: A genetically modified non-human mammal or cell characterised in that it does not comprise a nucleic acid sequence which itself encodes any endogenous immunoglobulin heavy chain constant region locus polypeptide.

Abstract: The present invention provides methods for studying pathogenesis of mammalian viruses. In particular, the present invention provides a nonhuman animal model system for studying disease mechanisms wherein the nonhuman animal model is infected with an animal virus. In a preferred embodiment the animal model is C. elegans and the animal virus is vesicular stomatitis virus (VSV).

Abstract: An I-CreI variant, wherein at least one of the two I-CreI monomers has at least two substitutions, one in each of the two functional subdomains of the LAGLIDADG core domain situated respectively from positions 26 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from the human IL2RG gene. Use of said variant and derived products for the prevention and the treatment of X-linked severe combined immunodeficiency.

Abstract: The present invention describes transgenic animals with human(ized) immunoglobulin loci and transgenes encoding human(ized) Ig? and/or Ig? sequences. Of particular interest are animals with transgenic heavy and light chain immunoglobulin loci capable of producing a diversified human(ized) antibody repertoire that have their endogenous production of Ig and/or endogenous Ig? and/or Ig? sequences suppressed. Simultaneous expression of human(ized) immunoglobulin and human(ized) Ig? and/or Ig? results in normal B-cell development, affinity maturation and efficient expression of human(ized) antibodies.

Abstract: The invention concerns uranium-chelating peptides as well as their uses for decontaminating soils and water, and for detecting and treating people contaminated by uranium. Said peptides have a helix-loop-helix type structure comprising the sequence of a calmodulin loop including at least one mutation of neutral residues selected from the group consisting of S, T, C, H, Y, N and Q, of one, two or three residues of at least one of the four calmodulin calcium binding sites: site I: residues selected among D20, D22 and D24 residues; site II: residues selected among D56, D58 and N60 residues; site III: residues selected among D93, D95 and N97 residues; site IV: residues selected among D129, D131 and D133 residues; said positions being indicated with reference to the human calmodulin sequence.

Abstract: The present invention provides a method for diagnosing and detecting diseases associated with breast. The present invention provides one or more proteins or fragments thereof, peptides or nucleic acid molecules differentially expressed in breast diseases (BCAT) and antibodies binds to BCAT. The present invention provides that BCAT is used as targets for screening agents that modulates the BCAT activities. Further the present invention provides methods for treating diseases associated with breast.

Abstract: The invention provides novel polypeptides having phospholipase activity, including, e.g., phospholipase A, B, C and D activity, patatin activity, phosphatidic acid phosphatases (PAP) and/or lipid acyl hydrolase (LAH) activity, nucleic acids encoding them and antibodies that bind to them. Industrial methods, e.g., oil degumming, and products comprising use of these phospholipases are also provided.

Abstract: Methods for testing candidate drugs for treatment of age-related macular degeneration are provided. Ccl2-deficient, and Ccr2-deficient mice are used to determine the effect of candidate drugs and treatments on development of age-related macular degeneration. Also provided is a Ccl2-deficient, Ccr2-deficient dual knockout mouse, which is a useful animal model for age-related macular degeneration.