Abstract: Protein ubiquitylation, an essential post-translational modification, regulates almost every cellular process including protein degradation, protein trafficking, signal transduction, and DNA damage response in eukaryotic cells. The diverse functions of ubiquitylation are thought to be mediated by distinct chain topologies resulting from eight different ubiquitin linkages, chain lengths, and complexities. Currently, ubiquitin linkages are generally thought to be a critical determinant of ubiquitin signaling. However, ubiquitin chain lengths, another key element of ubiquitin signaling, have not been well documented especially in vivo situation during past three decades from the discovery of ubiquitin. The reason of this was simply because no method has been available for determination of ubiquitin chain length in endogenous ubiquitylated substrates. In the present invention, a practical technique for determining the actual length of substrate-attached polyubiquitin chains from biological samples is established.

Abstract: The present invention relates to cell specific therapeutic modality by using a region of the PLAP Promoter. The invention further relates to specific expression of therapeutically PLAP useful sequences for specific transcriptional activation of this gene. The invention also relates to the PLAP region which may be used alone or in combination with other regions like enhancer sequences that augment cell or tumour specific gene expression.

Abstract: The present invention provides a method for evaluating (predicting, etc.) an individual difference (the tendency of every individual) in terms of drug sensitivity and disease vulnerability, comprising using a gene polymorphism of a cyclic AMP responsive element binding protein gene or the like. The method for evaluating drug sensitivity and the method for evaluating disease vulnerability according to the present invention comprise associating a gene polymorphism of a cyclic AMP responsive element binding protein gene or a haplotype constituted by the gene polymorphism with the drug sensitivity and disease vulnerability of an individual.

Abstract: A antibody has as a target molecule a ubiquitin protein comprising a phosphorylated serine residue at position 65. In addition, a method is provided for specifically detecting Parkinson's disease at an early stage, in which a target molecule is a ubiquitin protein comprising a phosphorylated serine residue at position 65, a pharmaceutical composition for definitively treating or preventing Parkinson's disease, and a method for screening for the pharmaceutical composition.

Abstract: The present invention has the object of providing a cell into which a protein, which can serve as a polymerization nucleus of a protein polymer, or polymer thereof is introduced, and a method for producing the cell. The invention relates to a cell into which a protein, which can serve as a polymerization nucleus of a protein polymer, or a polymer thereof is introduced, a method for producing the cell, and a method of screening for a compound inhibiting an intracellular accumulation of a protein containing fibril structures, wherein the method comprises bringing a candidate substance into contact with the cell.

Abstract: The present invention provides antibodies useful for diagnosing and treating tumors as well as methods of screening for antitumor agents. More specifically, tumors can be diagnosed and treated using an anti-phosphorylated p62 antibody that recognizes phosphorylation of serine at position 351 of an amino acid sequence of SEQ ID No. 1 or at a position corresponding thereto. An antitumor agent can be obtained by screening for a substance that inhibits the phosphorylation or that dephosphorylates the phosphorylated serine.

Abstract: The purpose of the present invention is to develop a method for amplifying in vitro to a large amount of a homogenous insoluble aggregate that is equivalent to an insoluble aggregate formed in the brain of a patient. A method of producing an insoluble aggregate including TDP-43 protein and fragments thereof according to the present invention includes the steps of: (1) introducing an insoluble fraction originated from the brain of a neurodegenerative disease patient into a cell culture in which the intact TDP-43 protein can be expressed in a constitutive manner; (2) culturing the cultured cell into which the insoluble fraction has been introduced; and (3) separating an insoluble fraction from the cultured cell. Optionally, the method may additionally include a step of amplifying the insoluble aggregate of the neurodegenerative-disease-related protein in the cultured cell.

Abstract: This invention relates to a high affinity recombinant humanized antibody fragment (scFv) specific for hepatitis B surface antigen having unique inter/intra chain bonding interaction because of 28 altered amino acid residues from the original mouse (5S) antibody and its chimeric Fab form, wherein fine tuning of the vernier zone residue makes it closer to the human sequence without any structural constraints.

Abstract: The present invention provides a pharmaceutical composition comprising a protein having ?-galactosidase activity for treating Fabry disease, which causes no allergic side effect, which is highly stable in blood (plasma) and which can readily be taken up by a cell of an affected organ. The pharmaceutical composition for treating Fabry disease of the invention comprises, for example, a protein which acquires an ?-galactosidase activity through alteration of the structure of the active site of wild-type human ?-N-acetylgalactosaminidase.

Abstract: The present invention provides, as an enzyme which can be used for enzyme replacement therapy for Fabry disease, a protein having ?-galactosidase activity, which shows no allergic adverse side effect, shows a high stability in blood, and can be easily incorporated into a cell of an affected organ. The protein of the present invention is a protein which has acquired ?-galactosidase activity by changing the structure of the active site of wild-type human ?-N-acetylgalactosaminidase.

Abstract: This invention relates to a novel non-obturation, regenerative technique “SealBio” of endodontic treatment involving regenerative potential of stem cells and signaling molecules, locally available in the peri-radicular region of teeth, wherein they are stimulated to induce healing and deposition of a natural barrier (seal) at the root apex.

Abstract: The present invention provides modified hepatitis C virus genomic RNA, comprising nucleotide sequences of genomic RNA portions of two or more types of hepatitis C viruses, which comprises a 5? untranslated region, a core protein coding sequence, an E1 protein coding sequence, a p7 protein coding sequence, an E2 protein coding sequence, an NS2 protein coding sequence, an NS3 protein coding sequence, an NS4A protein coding sequence, an NS4B protein coding sequence, an NS5A protein coding sequence, an NS5B protein coding sequence, and a 3? untranslated region, and which can be autonomously replicated. In particular, the present invention relates to modified hepatitis C virus genomic RNA, which can be autonomously replicated by substitution of the RNA sequence portion encoding NS3, NS4, NS5A, and NS5B proteins of hepatitis C virus genomic RNA with a partial RNA sequence encoding NS3, NS4, NS5A, and NS5B proteins of a JFH1 strain shown in SEQ ID NO: 1.

Abstract: Disclosed is a transformed cell (a cell model) which can form a cytoplasmic inclusion body derived from TAR DNA-binding protein of 43 kDa (TDP-43) that is found in the brain of a patient suffering from a neurodegenerative disease such as FTLD and ALS. The transformed cell is characterized by having, introduced therein, a promoter capable of functioning in a host cell and a mutant TDP-43 gene.

Abstract: The present invention was accomplished for the purpose of developing a method for effectively treating and/or preventing synucleinopathies, and is based on a discovery that an adiponectin receptor agonist suppresses ? (alpha)-synuclein aggregation, tau phosphorylation and a decrease in proteasomal activity. The method of the present invention for treating and/or preventing neurodegenerative diseases includes a step of administering an effective dose of at least one effective element selected from a group consisting of: adiponectin as an adiponectin receptor agonist; a compound inducing expression of adiponectin; globular adiponectin; and a compound inducing expression of globular adiponectin. The present invention further provides a screening method of the adiponectin receptor agonist for treating and/or preventing neurodegenerative diseases.

Abstract: The present invention provides antibodies useful for diagnosing and treating tumors as well as methods of screening for antitumor agents. More specifically, tumors can be diagnosed and treated using an anti-phosphorylated p62 antibody that recognizes phosphorylation of serine at position 351 of an amino acid sequence of SEQ ID No. 1 or at a position corresponding thereto. An antitumor agent can be obtained by screening for a substance that inhibits the phosphorylation or that dephosphorylates the phosphorylated serine.

Abstract: An objective of this invention is to provide an HCV strain with a high capacity for virus production in a cell culture system. This invention provides a nucleic acid encoding a polyprotein precursor of the hepatitis C virus JFH1 strain having one or more amino acid substitutions, wherein the polyprotein precursor comprises at least substitution of glutamine at position 862 with arginine, as determined with reference to the amino acid sequence as shown in SEQ ID NO: 2 in the Sequence Listing.

Abstract: The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.

Abstract: Provided is a recombinant virus which is efficacious in preventing the onset of hepatitis C infection and has a high safety. Also provided is a vaccine for hepatitis C virus which contains the recombinant virus. A recombinant vaccinia virus which can express hepatitis C virus gene. The hepatitis C virus vaccine as described above contains the recombinant virus as described above.

Abstract: The present inventors focused on siE sequences that have been thought to show RNAi activity against HCV viral RNAs, and mainly selected the D5-50 and D5-197 regions present within the IRES region, and carried on the analysis. As a result, the present inventors successfully identified siRNA sequences that exhibit a more effective RNAi activity against hepatitis C virus RNAs. Furthermore, the siRNAs were demonstrated to have a significant inhibitory effect on HCV propagation in an in vivo system.

Abstract: The present invention provides an antibody that specifically binds to an abnormal TDP-43 protein aggregate, an agent comprising the antibody for detecting a TDP-43 proteinopathy lesion, and a method for detecting or diagnosing a TDP-43 proteinopathy lesion by using the antibody.