Abstract: Pharmaceutical compositions comprising a nucleic acid, a gene delivery polymer, and at least one adjunctive chemotherapeutic drug for the treatment of mammalian cancer or hyperproliferative disorders and methods of using thereof for the treatment of mammalian cancer or hyperproliferative disorders by intratumoral, intraperitoneal or systemic injection.

Abstract: Disclosed herein are methods of producing pancreatic hormone-expressing cells by first differentiating pluripotent cells in cell culture so as to produce endodermal cells, the endodermal cells being competent to further differentiate into hormone-expressing cells capable of secreting at least one pancreatic hormone in response to a physiological signal, and then, transplanting the cultured endodermal cells into an organism, such as an organism in need of an endocrine cell therapy.

Abstract: The present invention describes the use of a mutant form of EtxB or CtxB to deliver an agent to a target cell wherein the mutant has GM-1 binding activity; but wherein the mutant has a reduced immunogenic and immunomodulatory activity relative to the wild type form of EtxB or CtxB.

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 mutations in a glucagon receptor gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions. The present invention also relates to diabetes and diabetic condition, as it demonstrates the role of the glucagon receptor in diabetes and diabetic conditions. The present invention further relates to weight gain and weight related conditions, such as obesity, and demonstrates the role of the glucagon receptor in weight gain and weight related conditions, such as obesity.

Abstract: Provided are in vivo screening methods to detect and identify substances that affect neuronal viability, and/or prevent neurodegeneration, and/or confer neuroprotective effects. The screening methods utilize recombinant C. elegans expressing a detectable marker in neuronal sub-groups and the use of neurotoxins specific to specific neuronal cells. Also provided are methods for identifying modulators of neurotransmitter transporters such as the dopamine transporter. Therefore, the invention provides methods for identifying substances that can be used in the prevention and therapy of neurodegenerative diseases.

Abstract: The invention provides genetically-modified non-human mammals and genetically-modified animal cells containing a functionally disrupted PDE11A gene. Also provided by the invention are methods of screening for agents that modulate PDE11A to modulate spermatogenesis, methods of treating mammals to modulate spermatogenesis, and methods of modulating cAMP and cGMP signal transduction in cells that express PDE11A.

Abstract: This invention provides transgenic mammals other than man carrying the gene of the human complement inhibitor (DAF/CD55) and expressing the human complement inhibitor in their organs and tissues, particularly in their endothelial cells. This invention provides nonhuman transgenic mammals useful as laboratory animals in the medical and pharmacological fields and/or sources of organs, tissues, cells and the like for medical treatment of man.

Abstract: Several genes encoding subunits of the neuronal nicotinic acetylcholine receptors have been cloned and regulatory elements involved in the transcription of the &agr;:2 and &agr;:7-subunit genes have been described. Yet, the detailed mechanisms governing the neuron-specific transcription and the spatio-temporal expression pattern of these genes remain largely uninvestigated. The &bgr;2-subunit is the most widely expressed neuronal nicotinic receptors subunit in the nervous system. We have studied the structural and regulatory properties of the 5′ sequence of this gene. A fragment of 1163 bp of upstream sequence is sufficient to drive the cell-specific transcription of a reporter gene in both transient transfection assays and in transgenic mice. Deletion analysis and sit-directed mutagenesis of this promoter reveal two negative and one positive element. The positively acting sequence includes one functional E-box.

Abstract: Using the nontoxic PA protein from B. anthracis, a method and composition for use in inducing an immune response which is protective against anthrax in subjects is described.

Abstract: Disclosed is a transgenic knockout mouse whose genome has a homozygous disruption in its endogenous Gpx1 and Gpx2 genes, wherein the disruptions result in a decrease in GPX activity in the transgenic mice when compared to non transgenic mice of the same type. Methods for production of the mouse are presented. Also disclosed are cells derived from the transgenic knockout mouse. The invention further provides a mouse model for the disorders of ileitis, colitis,inflammatory bowel disease, ileal cancer and myeloleukemia. The mouse can be used in a method for identifying therapeutic agents for the treatment of an individual diagnosed with one or more of said disorders.

Abstract: A preparation and a method of making composite blastocysts (CBs) from aggregates of dissociated cells of non-viable pre-embryos are disclosed. The CB is characterized morphologically by having two distinct tissue types, the inner cell mass (ICM) and the trophectoderm (TE), and a blastocoelic cavity (BC). The method of making CBs is an aggregation process (AP) comprising inter alia the following steps: 1) dissociation of discarded pre-embryos; 2) isolation of single nucleated cells from dissociated discarded pre-embryos; 3) microsurgical encapsulation of several cells within a host zona pellucida or artificial aggregation with or without a non-zona vessel; and 5) primary culture of the cell aggregates for multiplication and differentiation of cells. One particularly advantageous embodiment is that the starting material is non-viable pre-embryos. Another advantageous embodiment is that the AP allows individual cells from non-viable pre-embryos to further multiply, and become integrated into CBs.

Abstract: Methods are disclosed for screening for the occurrence of gene silencing (e.g., post transcriptional gene silencing) in an organism. Also provided are methods for isolating silencing agents so identified.

Abstract: This work constitutes a novel approach and methodology, e.g., the in vitro secretion method to isolate the androgenic polypeptide hormone (AH) from the androgenic gland of shrimp or prawns. Alternatively, the AH can be obtained recombinantly by cloning and expressing the AH gene. The AH polypeptide is used to produce phenotypic males, neomales, from genotypic female shrimp or prawns. The neomales find use in the production of sex-skewed and monosex offspring when mated with wild-type female shrimp or prawns. From the sequence of the purified AH polypeptide, oligonucleotide probes are synthesized to clone the AH encoding nucleic acid which is used for recombinant AH polypeptide expression.

Abstract: The present invention highlights the role of acetyl-CoA carboxylase through its product malonyl-CoA in regulating fatty acid oxidation and synthesis, glucose metabolism and energy homeostasis. It discloses transgenic mice with inactivating mutations in the endogenous gene for the acetyl-CoA carboxylase 2 isoform of acetyl-CoA carboxylase. Inactivation of acetyl-CoA carboxylase 2 results in mice exhibiting a phenotype of reduced malonyl-CoA levels in skeletal muscle and heart, unrestricted fat oxidation, and reduced fat accumulation in the liver and fat storage cells. As a result, the mice consume more food but accumulate less fat and remain leaner than wild-type mice fed the same diet. The instant invention provides a useful animal model to regulate malonyl-CoA production by ACC2 in the regulation of fatty acid oxidation by muscle, heart, liver and other tissues. They also identify potential inhibitors for studying the mechanisms of fat metabolism and weight control.

Abstract: Nematodes, such as Caenorhabditis elegans, that express mutant and wild-type orthologs of human genes involved in polycystic kidney diseases (PKDs), are used to study the functions of the proteins encoded by the genes, to screen for other genes involved in the diseases, to identify mutations involved in the diseases, and to screen for drugs that affect PKD. Behaviors controlled by the action of the genes or gene products are identified and used in the assays. Hence an animal model is provided that permits study of the etiology of polycystic kidney disease and provides a tool to identify the genes involved in the disease pathway, and to identify compounds that may be used to treat or alter the disease progression, lessen its severity or ameliorate symptoms. The nematode genes that encode protein products, mutants of the genes, vectors contain the genes and mutant genes and nematode strains that contain the vectors are also provided.

Abstract: A new method for identifying and eliminating chickens that are susceptible to pulmonary hypertension uses micrometer scale particles to occlude blood vessels in the lungs of the chickens. This results in the death of chickens that are pre-disposed to pulmonary hypertension. The invention effectively culls a chicken stock of the weaker animals.

Abstract: The object of the invention is a novel sensitization process for antigen-presenting cells, novel means for implementing the process and novel membrane vesicles possessing immunogenic potency. The invention relates in particular to texosomes (vesicles derived from tumor cells) and dexosomes (vesicles derived from dendritic cells loaded or not with antigens), and their use for the vectorization and presentation of antigens in vitro or in vivo as well as in methods or compositions for the treatment of cancers and infectious, parasitic or autoimmune diseases in particular.

Abstract: Novel insect toxins are disclosed for use in pesticidal compositions and methods. According to the invention basement membrane degrading proteases are identified which are capable of acting as insecticidal agents. Polynucleotides are provided which include expression constructs for the expression of the recombinant insecticidal proteases of the invention as recombinant insect pathogens, as well as transgenic plants with a substantial degree of insect resistance.

Abstract: The present invention provides polynucleotides and polypeptides of a murine sphingosine-1-phosphate phosphatase, referred to herein as mSPP1. The polynucleotides and polypeptides are used to further provide expression vectors, host cells comprising the vectors, probes and primers, antibodies against the mSPP1 protein and polypeptides thereof, assays for the presence or expression of mSPP1 and assays for the identification of compounds that interact with mSPP1.

Abstract: The invention provides methods of screening compounds for potential pharmacological activity using nematode worms, principally but not exclusively the nematode C. elegans. Specifically, the invention relates to the use of nematodes modified to have certain characteristics which provide advantages for compound screening, such as constitutive pharyngeal pumping, increased gut permeability or altered gut molecular transport. Methods for selecting suitably modified nematodes from a population of nematodes are also provided.