Lysosomal membrane permeabilization is an evolutionarily conserved hallmark of stress-induced cell death. Here the inventors show that the major stress-inducible heat shock protein 70 (Hsp70) enhances cell survival by stabilizing lysosomes through a pH-dependent high affinity binding to an endo-lysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP; also referred to as lysobisphosphatidic acid). The positively charged ATPase domain of Hsp70 is responsible for the binding but the substrate-binding domain is also required for effective stabilization of lysosomes. Importantly, the cytoprotective effect can be obtained by endocytic delivery of recombinant Hsp70 and specifically reverted by extra cellular administration of BMP antibodies or Hsp70 inhibitors. Thus, this protein-lipid interaction opens exciting possibilities for the development of cytoprotective and cytotoxic lysosome-specific therapies for the treatment of degenerative diseases and cancer, respectively.

Use of chaperones as autophagy receptors. The inventors identify a new function of the chaperones in aggrephagy. The chaperones are as a new type of autophagy receptor regulating the clearance of aggregation-prone proteins in cell and mouse brain.

The present invention concerns a method for modulating the enzymatic activity of an enzyme, wherein said enzyme interacts with BMP, said method comprising the step of administering or inducing Hsp70, or a functional fragment or variant thereof, in a form suitable for allowing interaction between BMP and Hsp70, or said functional fragment or variant thereof, and thereby modulating the enzymatic activity of an enzyme interacting with BMP.

The present inventors identified many nuclear proteins contained in the extract of skin tissue by mass spectrometry, randomly selected multiple partial amino acid sequences of the nuclear proteins, chemically synthesized peptides consisting of the partial amino acid sequences, and examined their activity of mobilizing mesenchymal stem cells. As a result, it was found that these multiple peptides show the activity of mobilizing mesenchymal stem cells into peripheral blood, even though their amino acid sequences are completely different from each other. The inventors also found that fragment peptides of the nuclear proteins have therapeutic effects on diseases characterized by inflammation and abnormalities of the immune system (e.g., inflammatory bowel disease and psoriasis). Based on these findings, a new regenerative medicine technology that can overcome the problems of cell transplantation therapy is provided.

Nucleic acid agents for reducing or removing infestations of the Varroa destructor mite are described. Compositions comprising the nucleic acid agents and methods for controlling mite infestations using the nucleic acid agents and compositions are also disclosed.

A method for preparing neoplastically transformed cells from human-derived cells, including the step of introducing human telomerase catalytic subunit (hTERT) gene, SV40 small T antigen (SV40ST) gene, and an oligonucleotide derived from Alu7 sequence into the human-derived cells. A method for introducing a gene for neoplastically transforming human-derived cells, including incorporating human telomerase catalytic subunit (hTERT) gene, SV40 small T antigen (SV40ST) gene, and an oligonucleotide derived from Alu7 sequence into the same or different vectors, and introducing the genes into human-derived cells therewith. The methods of the present invention can be utilized upon induction of neoplastic transformation to various human normal cells in order to elucidate mechanisms for onset of cancer, so that the method can be effectively utilized in the search of a new drug discovery target molecule.

The present invention concerns a method for modulating the enzymatic activity of an enzyme, wherein said enzyme interacts with BMP, said method comprising the step of administering or inducing Hsp70, or a functional fragment or variant thereof, in a form suitable for allowing interaction between BMP and Hsp70, or said functional fragment or variant thereof, and thereby modulating the enzymatic activity of an enzyme interacting with BMP.

A method of treatment employing cardiac glycoside is disclosed. A prognostic assay and kit and method of use thereof are provided. The kit and assay are used to determine the likelihood of a diseased cell or tissue having a therapeutic response to treatment with a cardiac glycoside in a disease having an etiology associated with excessive cell proliferation. The kit and assay are used to determine the ratio of isoforms of the subunit of Na, K-ATPase obtained from the diseased cell or tissue. The kit can be used to predict the therapeutic responsiveness of cancer or tumor in a subject to treatment with a cardiac glycoside. The kit and assay can be incorporated in a method of treating a disease or disorder having an etiology associated with excessive cell proliferation with a composition comprising a cardiac glycoside.

The present invention provides novel mitochondrial fusion transcripts and related deletion molecules that are associated with UV exposure. Methods for in vivo and in vitro detection of mtDNA molecules and associated fusion transcripts is also provided, as is their use in the screening and testing of skin care products.

The invention relates to detection of drug insensitivity by detecting mutations in the p97 gene or the p97 gene product following treatment with a p97 inhibitor, and identification of drugs to overcome such drug insensitivity.