Abstract: Methods, devices and apparatus are disclosed for carrying out multiple chemical reactions, such as in situ synthesis of polynucleotides, on a surface comprising an array of discrete sites. Molecules are deposited at a predetermined number of the discrete sites on the surface for reaction at the discrete sites. The surface is positioned relative to an outlet of a fluid ejection device, which is activated to dispense a small volume of a fluid through the outlet to the surface to provide uniform coating of a continuous region of the surface comprising a multiple of the discrete sites. The fluid is dispensed as uniform particles having a diameter such that the uniform particles form a sheet to coat the continuous region of the surface. In one embodiment of the present invention, liquid is dispensed as uniform particles through a fluid ejection device activated by means of ultrasonic energy. The invention has particular application to the in situ synthesis of polynucleotides in arrays on a surface.

Abstract: Disclosed are substantially pure AGE-1 polypeptides and purified DNAs, vectors, and cells encoding those polypeptides. Also disclosed are methods for determining longevity and isolating antagonists using the AGE-1 sequence.

Abstract: This invention relates to methods for producing a transgenic C. elegans that expresses a human 7TMR pan-neuronally, such that said transgenic C. elegans exhibits a known phenotype. These transgenic C. elegans can be used in a variety of ways, including, but not limited to: (1) screening and identifying substances that bind to and activate particular human 7TMRs; (2) screening for substances that antagonize human 7TMR activation; (3) identifying human 7TMRs that may respond to particular substances; and (4) evaluating the specificity and efficacy of substances on human 7TMR activation.

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 present invention concerns products and methods particularly useful for activating and analyzing non-dividing cell nuclei. The featured products include activating egg extracts, cytostatic factor (CSF) extracts, kits containing these extracts, and a microchamber microscope slide useful in analyzing nucleus activation.

Abstract: A method is provided for repopulating degenerated of immunetolerant mice which lack mature B and T lymphocytes with xenogenic mammalian hepatocytes, particularly primate hepatocytes to generate chimeric mice. In addition, a method of generating a human hepatitis virus-infected chimeric mouse is provided. A preferred xenogenic primate hepatocyte is derived from human, chimpanzee or baboon. These chimeric mice are useful in the investigation of host and viral mechanisms determining hepadnaviral persistence and hepatocarcinogenesis. Methods for monitoring the development of hepatitis and hepatocellular carcinoma as well as methods for testing and screening anti-viral and anti-cancer compounds with this model system are also provided.

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: Disclosed is a TGC method for inducting targeted somatic transgenesis in an animal host, whereby bacteria with a foreign DNA integrated into an episomal vector release, under the control of eukaryotic regulatory elements for ulterior transcription and expression, said foreign DNA in the case of infection of a foreign organism, organ, tissue, cell line or individual cells, causing transcription and expression of foreign DNA and/or foreign protein in said location.

Abstract: Methods are provided for restoring wild-type p53 gene function to a cell. Such methods include gene therapy. Typically, this will stop tumor cells from proliferating.

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: Disclosed is the sequence of the human ABC1 promoter, a method for expressing foreign DNA in host cells using the human ABC1 promoter, including a method of determining whether a chemical not previously known to be a modulator of the human ABC1 gene transcriptionally modulates the expression of the human ABC1 gene. Also disclosed is a sterol-responsive region of the human ABC1 promoter, along with a showing that it is activated by hydroxysterols and 9-cis-retinoic acid, implicating a mechanism of activation involving LXR/RXR heterodimers.

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: Compositions and methods for using mammalian CCR8 receptor proteins, antagonists and related reagents to treat diseases or conditions associated with Th2-mediated responses in an individual, especially asthma, are provided. The methods comprise administering a therapeutically effective amount of a CCR8 antagonist, alone or in combination with other therapeutic reagents. Also provided are methods for screening for therapeutics. Genetically-engineered animals and their use as models of molecular mechanism are also provided.

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.