This disclosure provides, among other things, strategies for minimizing antibody diversification in a transgenic animal that uses gene conversion for antibody diversification. In some embodiments, the animal may comprise a genome comprising an endogenous immunoglobulin light chain locus comprising: (a) a functional immunoglobulin light chain gene comprising a nucleic acid encoding a light chain variable region; and (b) a plurality of pseudogenes that are operably linked to the functional immunoglobulin light chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding a light chain variable region, wherein the pseudogenes are upstream or downstream of the functional immunoglobulin light chain gene and encode the same amino acid sequence as the light chain variable region of the functional immunoglobulin light chain gene of (a). In other embodiments, the locus may have a tandem array of coding sequences for the light chain.

This document provides methods and materials involved in treating mammals having a neurological disorder in the brain (e.g., Alzheimer's disease). For example, methods and materials for administering a composition including exogenous nucleic acid encoding a NeuroD1 polypeptide to a mammal having a neurological disorder in the brain are provided.

The present disclosure provides agents, compositions, and methods for inhibiting necroptosis in the brains of subjects in need thereof. In some embodiments, agents, compositions, and methods provided herein are useful for treating necroptosis-mediated neurovascular or neurodegenerative diseases or disorders, e.g., Alzheimer's disease.

The present invention encompasses filamin A (FLNA) binding proteins. Specifically, the invention relates to antibodies to FLNA. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Methods of making and methods of using the antibodies of the invention in methods of diagnosis, monitoring and prognosis or prostate cancer are also provided.

The present invention relates to methods for prolonging the survival of a primate that is transplanted a genetically modified heart, kidney, lung or liver from a xenogeneic mammal in a life supporting technique, and to compositions for use in a method of prolonging the survival of a primate that has been transplanted a genetically modified heart, kidney, lung or liver from a xenogeneic mammal in a life supporting technique. The invention is also directed to a living primate, whose heart, kidney, lung or liver is functionally substituted by a transplanted, genetically modified heart, kidney, lung or liver, respectively, from a xenogeneic mammal. Finally, the invention is directed to a genetically modified mammal and a donor organism for xenogeneic organ transplants as well as to methods of producing same.

The disclosure provides, among other things, compositions and methods useful for maintaining splicing fidelity in a cell. The compositions can include a compound that modulates the expression level or activity of one or more components of the spliceosome complex in a cell. In some embodiments, the compound is useful for restoring the expression level or activity of one or more splicing complex components to the expression level or activity present in the cell at an earlier chronological age. In some embodiments, the compound is useful for modulating the expression level or activity of one or more splicing complex components in the cell to the expression level or activity present in the cell under caloric restriction.

The present disclosure relates to methods of generating antibodies with improved specificity and/or affinity for a target antigen, as well as B-cells and hybridomas expressing the antibodies and compositions comprising antibodies with improved specificity and/or affinity for the target antigen.

Methods for elucidating biopolymer interactions with known and/or unknown small molecules (e.g. candidate drug compounds) are disclosed. These methods utilize novel (usually motile) organisms transformed with one or more heterologous biopolymer sequences. Biopolymer expression is promoted in cells mediating movement in said organism, generally dually-promoted in paired sets of cells mediating oppositely-directed movement. Modulation of motility in the resultant organism due to the presence of small molecules demonstrates small molecule interaction with said natural and/or mutated biopolymer. Analyzed in a chemical gradient, one or more interacting small molecule species can be identified by oriented migration, even in the presence of one or more non-interacting small molecule species. A competing and/or interfering biopolymer can be introduced without obscuring the motility signal. Methods described herein have utility for the discovery of novel therapeutic compounds (drug discovery), for the improvement of existing therapeutic compounds (drug refinement), and for the precise identification of small molecule binding sites on biopolymers via mutagenesis (structural elucidation). A specific embodiment, a Nematode Olfaction-based Structural Elucidation (NOSE) assay, is described herein.

This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

Various aspects described herein provide methods of generating alveolar or alveolar/airway organoids from a population of lung cells to differentiate into alveolar or alveolar/airway organoids. Also provided herein are methods and compositions for treating lung disease comprising transplantation of the alveolar or alveolar/airway organoids, or a cell isolated therefrom to a subject.