Abstract: The present invention provides novel polynucleotides encoding Drosophila DmTNF polypeptides, fragments and homologs thereof. The present invention also is directed to novel polynucleotides encoding two Drosophila DmTNF variants, DmTNFv1 and DmTNFv2 polypeptides, fragments and homologs thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention, in addition to methods of genetically modifying Drosophila or cultured cells to express or mis-express DmTNF, DmTNFv1, or DmTNFv2. The invention also relates to the use of such modified insects or cells to characterize DmTNF activity, identify TNF-like genes and/or genes implicated in modulating TNF, characterize TNF signaling pathways, and/or to identify modulators of DmTNF activity.

Abstract: A high throughput virus in vitro infectivity assay method comprising growing cells in a multi-well format, infecting the cells with intact virion incubated with a test agent, and measuring expression of at least one viral nucleic acid sequence in the cells. The method also preferably comprises incubating intact virion without test agent to define a control. The cells are preferably human keratinocyte cells grown in monolayers. The viral nucleic acid sequence will generally comprise viral mRNA. In one preferred embodiment, the intact virion comprise Human Papilloma Virus, and more preferably Human Papilloma Virus-11. Measuring expression is generally carried out by releasing the viral mRNA from the cells by lysis, amplifying the mRNA as CDNA via RT-PCR, and detecting amplicons with specific probes. Cell lysis may be carried out by heating or by treatment with detergent.

Abstract: This invention provides isolated nucleic acid of the p-Hyde gene, analogs, fragments, mutants, and variants thereof of the p-Hyde family. The invention provides polypeptides, fusion proteins, chimerics, fusion proteins, antisense molecules, antibodies, and uses thereof. Also, this invention is directed to a method of inducing susceptibility to apoptosis with p-Hyde, a method of suppressing tumor growth with p-Hyde, and a method of treating a subject with cancer with p-Hyde alone or in combination with radiation, chemotherapy, or UV mimetic drugs. The invention also relates to the therapy of human cancers which have a mutation in the p-Hyde gene, including gene therapy, protein replacement therapy and protein mimetics. The invention further relates to the screening of drugs for cancer therapy. Finally, the invention relates to the screening of the p-Hyde gene for mutations, which are useful for diagnosing the predisposition to cancer.

Abstract: Described herein is Zscan4, a gene exhibiting 2-cell embryonic stage and embryonic stem cell specific expression. Identification of nine Zscan4 co-expressed genes is also described. Inhibition of Zscan4 expression inhibits the 2-cell to 4-cell embryonic transition and prevents blastocyst implantation, expansion and outgrowth. Provided herein are methods of inhibiting differentiation of a stem cell, promoting blastocyst outgrowth of embryonic stem cells and identifying a subpopulation of stem cells expressing Zscan4. Further described is the identification of Trim43 as a gene exhibiting morula-specific expression. Also provided are isolated expression vectors comprising a Zscan4 promoter, or a Trim43 promoter operably linked to a heterologous polypeptide and uses thereof. Further provided are transgenic animals comprising transgenes encoding marker proteins operably linked to Zscan4 and Trim43 promoters.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Specifically, the present invention identifies and describes genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in cardiovascular disease. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease.

Abstract: The invention provides an isolated gene encoding Mch4 or an isolated gene encoding Mch5 as well as functional fragments thereof. Also provided are isolated nucleic acid sequences encoding Mch4 or Mch5 or functional fragment thereof The gene or nucleic acid sequences can be single or double stranded nucleic acids corresponding to coding or non-coding strands of the Mch4 or Mch5 nucleotide sequences. Also provided are genes and nucleic acids encoding functional fragments such as the FADD-like domains Mch4A, Mch4B, Mch5A and Mch5B. Isolated Mch4 or Mch5 polypeptides or functional fragments thereof including the FADD-like domains Mch4A, Mch4B, Mch5A and Mch5B are also provided.

Abstract: The present invention relates to utrons, RNA molecules which contain promoter regulatory motif(s) and DNA analogs thereof and DNA molecules that can be transcribed to produce the foregoing. In particular, the invention provides gene promoter suppressing nucleic acids which suppress transcription from a promoter of interest. In a preferred embodiment, the invention provides the TSU gene, nucleotide sequences of the TSU gene and RNA, as well as fragments, homologs and derivatives thereof. Methods of isolating TSU genes are also provided. Therapeutic and diagnostic methods and pharmaceutical compositions are also provided. In particular, the invention relates to methods for cell replacement therapy, gene therapy or organ transplantation wherein TSU nucleic acids suppress MHC class I and II gene expression, thus preventing immuno-rejection of non-autologous cells or organs.

Abstract: It was revealed that the intravenous administration of HMGB-1 and S100A8 promoted the healing of skin ulcer by recruiting bone marrow-derived cells to the site of skin ulcer. Furthermore, when HMGB-1 was intravenously administered to cerebral infarction model mice after creation of cerebral infarction, bone marrow-derived cells expressing nerve cell markers were detected in their brain. A marked cerebral infarct-reducing effect was observed in mice intravenously administered with HMGB-1 as compared to the control. The post-cerebral infarction survival rate was increased in the intravenous HMGB-1 administration group. The involvement of bone marrow pluripotent stem cells in the process of bone fracture healing was assessed using mice, and the result demonstrated that bone marrow-derived cells distant from the damaged site migrated to the bone fracture site to repair the damaged tissue.

Abstract: The aim of the present invention is to provide a method of acquiring immunological tolerance to a foreign DNA or its expression product whereby the foreign DNA such as a vector carrying a foreign gene incorporated thereinto or its expression product can be recognized not as non-self but as self; a method of sustaining a gene therapeutic effect whereby a rejection to a foreign DNA such as a vector carrying a foreign gene incorporated thereinto or its expression product can be avoided; and a non-human animal which has acquired immunological tolerance to a foreign DNA such as a vector carrying a foreign gene incorporated thereinto or its expression product. Fetal immature T lymphocytes transferred with a foreign DNA, such as a foreign gene-incorporated viral vector, are introduced into thymus and said foreign DNA is expressed in the thymus organ.

Abstract: There is provided a method of inducing differentiation of bone marrow stromal cells to neural cells or skeletal muscle cells by introduction of a Notch gene. Specifically, the invention provides a method of inducing differentiation of bone marrow stromal cells to neural cells or skeletal muscle cells in vitro, which method comprises introducing a Notch gene and/or a Notch signaling related gene into the cells, wherein the finally obtained differentiated cells are the result of cell division of the bone marrow stromal cells into which the Notch gene and/or Notch signaling related gene have been introduced. The invention also provides a method of inducing further differentiation of the differentiation-induced neural cells to dopaminergic neurons or acetylcholinergic neurons. The invention yet further provides a treatment method for neurodegenerative and skeletal muscle degenerative diseases which employs neural precursor cells, neural cells or skeletal muscle cells produced by the method of the invention.

Abstract: Provided are hydrolases, including lipases, saturases, palmitases and/or stearatases, and polynucleotides encoding them, and methods of making and using these polynucleotides and polypeptides. Further provided are polypeptides, e.g., enzymes, having a hydrolase activity, e.g., lipases, saturases, palmitases and/or stearatases and methods for preparing low saturate or low trans fat oils, such as low saturate or low trans fat animal or vegetable oils, e.g., soy or canola oils.

Abstract: The present invention relates to the diagnosis and treatment of cancer, and in particular breast cancer. Specifically, in some embodiments the invention relates to methods of diagnosing cancer, and in particular breast cancer, using an antibody specific for a gene product that localizes selectively to the endoplasmic reticulum of the cancer cell(s). In some embodiments, the invention relates to methods of treating cancer, and in particular breast cancer, by administering a composition comprising an RNA interference sequence (e.g., shRNA, RNAi and/or siRNA molecule) characterized by an ability to inhibit an mRNA molecule, which mRNA molecule is encoded by the C43 gene (SEQ ID NO: 1). The invention additionally relates to methods for detecting cancer cells by detecting reduced methylation of the C43 promoter, and methods for reducing cancer metastasis by using demethylation inhibitors that result in increased methylation of the C43 promoter.

Abstract: The invention relates to compositions of transfection comprising an oligonucleotide and an amphiphilic cationic molecule of formula (I) wherein, —X is N—R1, S or O, R1 being a C1-C4 alkyl radical or an hydroxylated C3-C6 alkyl radical, R2 and R3, identical or different, represent H or a C1-C4 alkyl radical, or R2 and R3 are linked together to form a saturated or unsaturated cycle or a heterocycle having 5 or 6 elements, E is a C1-C5 alkyl spacer, R4 and R5, identical or different, represent saturated or unsaturated, linear or branched, C10-C36 hydrocarbon or fluorocarbon chains, optionally comprising C3-C6 cycloalkyl, A? is a biocompatible anion. The invention relates to compositions active for oligonucleotides delivery into eukaryotic cells in culture, ex vivo or in vivo. The invention relates to compositions of transfection comprising an oligonucleotide active for RNA interference. Such compositions can be used as tools for biological studies or as drugs for therapies.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, particularly prostate cancer, are disclosed. Illustrative compositions comprise one or more prostate-specific polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases, particularly prostate cancer.

Abstract: pp32 is a member of a highly conserved family of differentiation-regulated nuclear proteins that is highly expressed in nearly all human prostatic adenocarcinomas of Gleason Grade ≧5. This contrasts with the low percentage of prostate tumors that express molecular alterations in proto-oncogens or demonstrate tumor suppressor mutation or loss of heterozygosity. By analysis of specimens of human prostatic adenocarcinoma and paired adjacent normal prostate from three individual patients, the inventors have shown that normal prostate continues to express normal pp32, whereas three of three sets of RT-PCR-amplified transcripts from prostatic adenocarcinomas display multiple cancer-associated coding sequence changes. The cancer-associated sequence changes appear to be functionally significant. Normal pp32 exerts antineoplastic effects through suppression of transformation. In contrast, cancer-associated pp32 variants augment, rather than inhibit, transformation.

Abstract: The present invention relates to a (first) method for producing inducible and/or repressible expression active linear RNA interference constructs comprising a PCR amplification of a source polynucleotide comprising the inhibitory RNA coding sequence of interest or comprising a PCR amplification of a DNA source comprising a promoter using a reverse primer comprising the inhibitory RNA coding sequence of interest. The present invention furthermore relates to a (second) method for producing inducible and/or repressible expression active linear gene constructs comprising a PCR amplification of a source expression polynucleotide comprising a promoter sequence and the DNA sequence of interest or comprising a PCR amplification using the DNA sequence as a template.

Abstract: In alternative embodiments, the invention provides nucleic acid sequences that are genetic polymorphic variations of the human TMEM216 gene, and TMEM216 polypeptide encoded by these variant alleles. In alternative embodiments, the invention provides methods of determining or predicting a predisposition to, or the presence of, a ciliopathy (or any genetic disorder of a cellular cilia or cilia anchoring structure, basal body or ciliary function) in an individual, such as a Joubert Syndrome (JS), a Joubert Syndrome Related Disorder (JSRD) or a Meckel Syndrome (MKS). In alternative embodiments, the invention provides compositions and methods for the identification of genetic polymorphic variations in the human TMEM216 gene, and methods of using the identified genetic polymorphisms and the proteins they encode, e.g., to screen for compounds that can modulate the human TMEM216 gene product, and possibly treat JS, JSRD or MKS.

Abstract: It has been discovered that there are at least two significant antigens present on the cells of animal species such as pigs that elicit an immune or inflammatory response immediately upon implantation into humans or contact with human serum. The first is an ?-galactosyl (Gal) epitope, for example, Gal?(1?3)Gal?(1?4)GlcNac (linear B type 2) or Gal? (1?3)Gal?(1?4)Glc (linear B type 6). The second is an N-glycolylneuraminic acid (NeuGc) structure. By eliminating these epitopes, preferably by genetically engineering the animal so that the epitope is either not produced or is greatly reduced, or by chemical or enzymatic treatment of the animal's cells to remove the epitopes, it is possible to produce organs, tissues and cells suitable for xenotransplantation into humans. Cells can be rendered even more compatible by genetically engineering the animal to express a human complement regulatory protein (inhibitor), such as CD59, on its cells, or to express an excess of a pig complement regulatory protein.

Abstract: The invention provides polynucleotides and polypeptides corresponding to novel gene sequences associated with the incidence of cardiovascular disorders. The invention also provides polynucleotide fragments corresponding to the genomic and/or coding regions of these genes which comprise at least one polymorphic site per fragment. Allele-specific primers and probes which hybridize to these regions, and/or which comprise at least one polymorphic site are also provided. The polynucleotides, primers, and probes of the present invention are useful in phenotype correlations, paternity testing, medicine, and genetic analysis. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders, particularly cardiovascular diseases related to these polypeptides.

Abstract: The invention provides isolated nucleic acids encoding a variety of proteins having diagnostic, preventive, therapeutic, and other uses. These nucleic and proteins are useful for diagnosis, prevention, and therapy of a number of human and other animal disorders. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies. Diagnostic, screening, and therapeutic methods using compositions of the invention are also provided. The nucleic acids and polypeptides of the present invention are useful as modulating agents in regulating a variety of cellular processes.