Abstract: The present invention is directed to recombinantly engineered mice that are deficient in the expression of both presenilin-1 and presenilin-2. The mice exhibit characteristics of age-dependent cognitive impairments and neurodegeneration similar to those seen in Alzheimer's disease patients. This presenilin-deficient mouse model can be used to screen compounds capable of slowing, preventing or reversing the progression of cognitive impairments and neurodegeneration. The invention is also directed to the development of treatments for Alzheimer's disease based on augmentation or restoration of presenilin function in the brain. On the basis of the findings described herein, the invention is further directed to the development of assays to detect functional presenilin deficiency in human individuals, preferably through analysis of presenilin substrates, which may provide biomarkers useful in the diagnosis of Alzheimer's disease.

Abstract: The present invention is to provide a non-human animal model of systemic lupus erythematosus wherein generation of anti-double stranded DNA antibody and anti-single stranded antibody is induced, and that is made to spontaneously develop glomerulonephritis and arthritis, and a screening method for a therapeutic agent for systemic lupus erythematosus wherein the non-human animal model is used. Fc?RIIB deficient mouse that is not made to spontaneously develop autoimmune pathology although its autoantibody response is enhanced is backcrossed into C57BL/6J (B6) mouse for 12 generations to generate Fc?RIIB deficient B6 mouse, the Fc?RIIB deficient B6 male mouse is intercrossed with lpr/B6 female mouse, and thus obtained Fc?RIIB+/?/lpr+/? mice were further crossed to generate a mouse model of systemic lupus erythematosus.

Abstract: This invention provides populations of neural progenitor cells and differentiated neurons, obtained by culturing pluripotent cells in special growth cocktails. The technology can be used to produce progenitors that proliferate through at least ˜40 doublings, while maintaining the ability to differentiate into a variety of different neural phenotypes, including dopaminergic neurons. The neural progenitors and terminally differentiated neurons of this invention can be generated in large quantities for use in drug screening and the treatment of neurological disorders.

Abstract: Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

Abstract: Provided is a method for determining whether an agent is an agonist of the neuron-specific calcium sensor-1 (NCS-1), for consideration of an agonist of NCS-1 as a drug candidate for therapy of a behavioral disorder or for improving learning and/or memory of a subject, said method comprising the steps of: (a) contacting a cell, tissue or non-human animal with an agent to be screened under conditions to permit neuron-specific calcium sensor-1 (NCS-1) activity; and (b) determining NCS-1 activity of said treated cell, tissue or non-human animal, wherein an increase in NCS-1 activity compared with a corresponding control cell, tissue or animal is indicative of an agent which is an agonist of NCS-1.

Abstract: The present invention relates to the use of nimesulide and structurally related compounds in the prevention and/or treatment of neurodegenerative conditions. It is based, at least in part, on the discovery that nimesulide exhibits a neuroprotective effect against ?-amyloid induced cell death. Without being bound to any particular theory, it appears that nimesulide inhibits a non-inflammatory mechanism of neurodegeneration.

Abstract: The present invention relates to novel methods and compositions for blocking transmission of Plasmodium vivax which cause malaria. In particular, Pvs25 and Pvs28 polypeptides, variants, including deglycosylated forms, and fusion proteins thereof, are disclosed which, when administered to a susceptible organism, induce an immune response against a 25 kD and 28 kD protein, respectively, on the surface of Plasmodium vivax zygotes and ookinetes. This immune response in the susceptible organism can block transmission of malaria.

Abstract: A DNA vaccine for the treatment of prostate cancer, comprising a plasmid vector comprising a nucleotide sequence encoding prostatic acid phosphatase (PAP) operably linked to a transcription regulatory element, wherein upon administration to a mammal a cytotoxic immune reaction against cells expressing PAP is induced. In preferred embodiment, the PAP encoded is a xenoantigen highly homologous to the autoantigen PAP of the mammal. Also disclosed are methods for inducing prostatitis, or inducing immune reaction to PAP, or treating prostate cancer in a mammal, using the DNA vaccine and pharmaceutical compositions comprising the vaccine. Preferably, xenoantigen vaccination is followed by boosting with autoantigen PAP from the same animal species as the mammal being treated.

Abstract: An object of the present invention is to provide a remedy for dysfunction of central monoamine pathway, a method for screening a PTP? inhibitor or activator, and a non-human model animal being hyposensitive to a stimulant drug, After administering a subject material to PTP? knockout mice and wild-type mice, PTP? activity in the PTP? knockout mice and the wild-type mice is compared and evaluated to screen a PTP? inhibitor or activator. Examples of the comparison and the evaluation of the PTP? activity include the comparison and the evaluation of the function of central monoamine pathway such as changes in the level of central monoamine metabolism, sensitivity to a stimulant drug, the presence of dysfunction of mesolimbic dopamine pathway, level of acclimation to new circumstances, or stress-responsiveness.

Abstract: The invention provides methods for producing myelin forming cells from multipotent self-renewing central nervous system neural stem cells as well as methods of using one or more cells from a multipotent self-renewing central nervous system neural stem cell population to form patches of myelin. Also provided are cell culture systems for forming patches of myelin and methods of treating demyelination diseases in a mammal.

Abstract: The present invention relates to the use of umbilical cord blood cells from a donor or patient to provide neural cells which may be used in transplantation. The isolated cells according to the present invention may be used to effect autologous and allogeneic transplantation and repair of neural tissue, in particular, tissue of the brain and spinal cord and to treat neurodegenerative diseases of the brain and spinal cord.

Abstract: Disclosed is a method for the recombinant production of biofilaments, such as spider silk or insect fibroins, using transgenic animals which secrete the biofilaments in their milk and/or urine, and transgenic cells which secrete the biofilaments into culture media. Such a method is useful for producing large quantities of biofilament material. Also disclosed is a nucleic acid molecule for generating such transgenic animals.

Abstract: The present invention is directed to compositions and methods related to the use of human OGC as an uncoupling protein.

Abstract: The present invention provides improved methods and compositions for the generation of transgenic non-human animals. The present invention permits the introduction of exogenous nucleic acid sequences into the genome of unfertilized eggs (e.g., pre-maturation oocytes and pre-fertilization oocytes) by microinjection of infectious retrovirus into the perivitelline space of the egg. The methods of the present invention provide an increased efficiency of production of transgenic animals with a reduced rate of generating animals which are mosaic for the presence of the transgene.

Abstract: The present invention provides a non-human model animal of Goodpasture's syndrome that contributes to the treatment of Goodpasture's syndrome where the development of therapy had been delayed due to the lack of adequate disease models, a method for screening a remedy for Goodpasture's syndrome by using the model animal, and a method for diagnosing Goodpasture's syndrome at the early stage. A Goodpasture's syndrome model mouse is constructed by immunizing immunoglobulin Fc? receptor IIB knockout mouse with type IV collagen, thereby inducing Goodpasture's syndrome. Moreover, a remedy for Goodpasture's syndrome is screened by administration of test substances to the Goodpasture's syndrome model mouse, followed by evaluating the severity of the expression of Goodpasture's syndrome as an index, such as diffuse alveolar hemorrhage, glomerulonephritis, the appearance of antikidney glomerular basement membrane antibody, and the like.

Abstract: A method for treating peripheral neuropathy, particularly ischemic peripheral neuropathy, is provided. The method involves administering to subjects in need of such treatment an effective amount of an angiogenic growth factor to alleviate a symptom of the neuropathy.

Abstract: The invention provides methods for the treatment of abnormal psychiatric states, particularly the negative symptoms of schizophrenia and extrapyramidal side effects (EPS) of antipsychotic drugs. The inventive methods relate to the administration of therapeutic cells (which produce dopamine or dopamine precursors) adhered to support matrices to subjects suffering from the negative symptoms of schizophrenia and/or EPS. The therapeutic cells may be coadministered with cells which protect the therapeutic cells from immune rejection and/or cells which produce neurotrophic factors which improve the viability of the therapeutic cells.

Abstract: The invention relates to a process for the determination of the ?-secretase activity, individual components of the process and the use of the process. The present invention relates to a novel process for the determination of the ?-secretase activity and for the detection of ?-secretase; particular embodiments of the process relate on the one hand to processes for the identification of a ?-secretase or of a cDNA which codes for a ?-secretase and on the other hand to processes for the identification of substances which can inhibit the activity of a ?-secretase. Such substances have particular importance, as they can be used, for example, as pharmaceutical active compounds, e.g. for the treatment of Alzheimer's disease.

Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.

Abstract: The invention discloses methods of proliferation and differentiation of multipotent neural stem cells. Also provided are methods of making cDNA libraries and methods of screening biological agents which affect proliferation differentiation survival phenotype or function of CNS cells.