The present invention provides Factor IX fusion proteins with higher specific activity and a longer useful clotting function relative to wild type or non-modified Factor IX protein.

The invention relates to nucleic acid constructs for expression in mice for the production of heavy chain only antibodies and V.sub.H domains, transgenic mice, related methods and uses.

Disclosed are compositions, methods, and kits for modifying DNA within cells as well as compositions and methods for modifying gene expression in a cell. In particular, the invention generally relates to compositions, methods, and kits for DNA editing using single-stranded DNA. Compositions and methods for modifying gene expression using artificial microRNAs (amiRNA) are also contemplated.

This document relates to non-human animal models (e.g., non-human mammalian models such as mouse models) for aging (e.g., neural aging). For example, non-human animal models having reduced or eliminated levels of aralkylamine N-acetyltransferase (AANAT) polypeptide expression are provided.

Provided herein is a method for treating and/or preventing various diseases including a decrease in glucose tolerance and a decrease in cognitive ability associated with aging with adipocytes over-expressing FFAR4 and a transplant composition including the adipocytes.

A method for screening an active ingredient of a saltiness enhancer, the screening method including the following steps: (i) a step for determining whether a test substance is a compound capable of promoting functional expression of the TMC4 gene or TMC4 protein; and (ii) a step for selecting, as an active ingredient of a saltiness enhancer, a test substance that has been determined in step (i) to be a compound capable of promoting functional expression of the TMC4 gene or TMC4 protein.

The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

The present disclosure provides a genetically modified mouse comprising a genomic nucleic acid encoding human APOE4, a genomic nucleic acid encoding mouse TREM2 modified to include a R47H substitution, and at least one genomic modification selected from the group consisting of: (a) a genomic nucleic acid encoding mouse ABCA7 modified to include an A 1541 G substitution; (b) a genomic nucleic acid encoding mouse APP modified to include G60IR, F606Y, and R609H substitutions; (c) a genomic nucleic acid encoding mouse PLCG2 modified to include a M28L substitution; (d) a genomic nucleic acid encoding mouse MTHFR modified to include a A262V substitution; (e) an inactivated Ceacaml allele; and (f) an inactivated II1rap allele. Methods of producing the genetically modified mouse and methods of using the genetically modified mouse are also provided.

The invention relates, in part, to methods to introduce gene alleles of interest into members of a population of a species. The invention also relates to methods to prepare large numbers of organisms comprising one or more introduced alleles of interest in an otherwise wild-type genome.

It is shown that ventral hippocampal kindling results in functional reorganization of the ventral hippocampal excitatory circuits. Most pronounced is the connectivity to the medial prefrontal cortex, with increased volume of activation on fMRI and increased amplitude of activation on electrophysiology. There is evidence of increased anxiety following kindling Methods are provided for simultaneous LFP-fMRI to image single seizures Imaging the spatiotemporal dynamics of individual seizures enables characterization of propagation patterns of focal and secondary-generalized seizures, that provide for targeted intervention.