Abstract: Genetically modified mice characterized by one or more symptoms or signs associated with expression of human APOE4p and mouse Trem2p and relevant to non-familial late-onset Alzheimer's disease are provided wherein the genome of the mouse includes: 1) a DNA sequence encoding a human APOE4 protein (APOE4p) operably linked to a promoter; and 2) a DNA sequence encoding a mouse Trem2 protein having a mutation p,R47H (Trem2p) operably linked to a promoter, such that the mouse expresses human APOE4p and mouse Trem2p. Methods ace provided for screening for a compound for use in the treatment of Alzheimer's disease using such genetically modified mice.

Abstract: Humanized mouse models and methods are provided for determining whether administration of an immunomodulatory drug likely elicits a severe cytokine release syndrome in a human. Humanized mouse models and methods are also provided for determining the immunotoxicity in a human of a drug candidate or of drug combinations.

Abstract: Provided herein, in some embodiments, are methods for modulating expression and/or activity of transient receptor potential cation channel subfamily C, member 3 (TRPC3), as well as methods of treating Alzheimer's disease.

Abstract: The present disclosure provides immunodeficient mouse models that comprise a nucleic acid encoding a human or humanized amyloid precursor protein (APP) and, in some models, further comprise a nucleic acid encoding a mutated human presenilin 1 protein (PSEN1). These mouse models are useful, for example, for Alzheimer's disease studies.

Abstract: Provided herein, in some embodiments, are novel methods for predicting response to a platinum-based chemotherapeutic agent in triple negative breast cancer and ovarian carcinoma.

Abstract: Provided herein are immnunodeficient mouse models engrafted with cells comprising a pathogen entry moiety, for example, for assessing pathogenic infection. The pathogen may be a virus, such as a respiratory virus.

Abstract: The present invention generally relates to uses of glial cell line-derived growth factor (GDNF) in cutaneous wound healing and hair growth. Methods of effecting hair growth and/or wound healing which feature administration of GDNF, or a biologically active fragment thereof, to subjects, e.g., human subject, are disclosed herein. The invention relates also to formulations and kits for achieving the indicated pharmaceutical advantages.

Abstract: Provided herein are antimicrobial biosensors for skin for treating Staphylococcus aureus Type I, Type II, Type III, and/or Type IV infection. In some embodiments, the antimicrobial biosensors are expressed in Staphylococcus epidermidis cells.

Abstract: Provided herein are methods of inhibiting type 1 receptor and/or type 2 receptor signaling in subjects, optionally subjects with diseases associated with myostatin, type 1 receptor, and/or type 2 receptor signaling, or muscle loss and/or bone deterioration. Also provided are compositions for inhibition of type 1 receptor and/or type 2 receptor signaling.

Abstract: Humanized mouse models and methods are provided for determining whether administration of an immunomodulatory drug likely elicits a severe cytokine release syndrome in a human. Humanized mouse models and methods are also provided for determining the immunotoxicity in a human of a drug candidate or of drug combinations.

Abstract: Provided herein are chemically modified antisense oligonucleotides that bind to sequences on mRNAs encoding the splicing factor TKA2?, associated with cancer.

Abstract: The present disclosure relates to genetically modified non-obese diabetic (NOD) mice deficient in murine class I MHC molecules, class II molecules, or both class I and class II MHC molecules. The MHC knockout transgenic mice provided herein are useful, for example, for developing therapies for diabetes.

Abstract: Provided herein, in some embodiments, are methods, compositions, and systems for identifying alternatively spliced tumor-specific exon inclusion and exclusion events that can be used for survival prognosis.

Abstract: Disclosed are bispecific molecules combining ACE2 with an anti-CD3 antibody and engineered T cells expressing chimeric antigen receptors that bind to SARS-CoV-2 spike protein, as well as related compositions and methods. The methods and compositions provided can be used for treating early-stage and/or late-stage SARS-CoV-2 infections, independent of the SARS-CoV-2 variant.

Abstract: The present disclosure provides immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG™) mouse models that comprise an inactivated mouse Flt3 allele and, in some models, additional genetic modifications. These mouse models useful, for example, for superior engraftment of diverse hematopoietic lineages and for immune-oncology, immunology and infectious disease studies.

Abstract: Systems and methods for continuous monitoring of the behavior of animals, such as small rodents, are provided. Monitoring can include video, audio, and other sensor modalities. In one embodiment, the system can include cameras, arena design, environmental sensors, and ultrasonic sensors. The system uniquely provides a continuous long-term monitoring system suitable for mouse behavioral study. Further provided is a neural network based tracker configured for use with video data acquired by the monitoring system. Three different neural network architectures have been tested to determine their performance on genetically diverse mice under varying environmental conditions. It has been observed that that an encoder-decoder segmentation neural network achieves high accuracy and speed with minimal training data.

Abstract: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/B1N, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2retmlWjl/SzJ (NSG), NOD.Cg-Rag1tm1Mom Il2rgtmlWjl/SzJ (NRG) and NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice.

Abstract: A NOD.Cg-PrkdcscidH2rgtm1 Wjl/SzJ.(NOD-scid-IL2r?null, NSG) mouse which is genetically modified such that the en NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present, invention. According to specific aspects the genetically modified NSG mouse, is a NOD.Cg-PrkdcscidH2-K1tml Bpe H2-Ab1eml Mvw H2-D1tml Bpe H2rgtm Wjl/SzJ (NSG-Kb Db)null(IAnull)) mouse, NSG-RIP-DTR (Kb Db)null(IAnull) mouse, or a NOD.Cg-B2mtmlUnePrKdcscidH2dlAb1-E?H2rgtm1 Wjl/SzJ (NSG-B2Mnull(IA IEnull)) mouse. Human, immune cells and/or human: tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.

Abstract: Provided herein are, inter alia, compositions and methods for demethylating and methylating a target DNA sequences in a mammalian cell. The compositions and methods are, useful for activity modulation of a targeted gene, or to create a gene regulatory network.

Abstract: Certain pressure sensor devices are much smaller than prior art devices, yet are at least as sensitive as the prior art devices. A capacitive pressure sensor can include a flexible substrate that permits bending of a pressure sensing region without significantly affecting operation thereof. The pressure sensor can include a flexible membrane in which an electrode is sandwiched between two layers of polymeric material. The sandwiched electrode can be extremely close to a reference electrode so as to provide for highly sensitive capacitance readings, yet the membrane can be restricted from contacting the reference electrode under high pressure condition.