The present invention relates to methods of treating cancer patients carrying one or more specific fusion genes. It is based, at least in part, on the discovery that the protein encoded by the MAN2A1-FER fusion gene exhibits kinase activity and the use of tyrosine kinase inhibitors targeting MAN2A1-FER in a cancer other than prostate, for example hepatocellular cancer, led to dramatic improvement of survival of animals xenografted with the cancer.

A method for preparing a CKO/KI animal model by using Cas9 technology includes a Cas9 protein expressed and purified in vitro, high-efficiency sgRNA(s) screened by sgRNA cleavage efficiency test on embryos in advance, and single-stranded DNA as targeting vector(s) are mixed with Cas9 protein and sgRNA(s) and then subjected to embryo injection and transplantation; mice born after transplantation are marked as F0 and the genotype identification of F0 is carried out; sexually mature F0 with the correct genotype are bred, and the offspring mice thereof are marked as F1; and the F1 mice are analyzed and verified, and the F1 mice with the correct genotype are the prepared CKO/KI animal model.

Provided herein are methods, systems, and related vectors and compositions allowing for noninvasive control of neural circuits. In particular, the methods and systems herein described utilize acoustically targeted chemogenetics to achieve a noninvasive neuromodulation in specifically selected cell-types among spatially selected brain regions.

Provided herein non-human transgenic animals comprising a genome that: i) under-expresses, or is inducible to under-express, Hu Antigen R (HuR) in at least some neurons of said transgenic animal; ii) does not express HuR, or is inducible to not express HuR, in at least some neurons of said transgenic animal; or iii) does not express functional HuR, or is inducible to not express functional HuR in at least some neurons of said transgenic animal, as well as methods of screening drugs and therapies (e.g., useful in treating ALS) using such animals.

The invention provides for transgenic donor animals (e.g., pigs) whose cells, tissues and organs have a better long-term survival when transplanted into a human patient. The transgenic donor animal carries one or more human transgenes which is expressed only when the endogenous gene of the donor animal is knocked out shortly before a graft is harvested for transplantation. This “genetic switch” allows the donor animal to remain healthy during the majority of its lifetime, while still allowing expression of the human transgene for optimal transplant tolerance in a human recipient. The transgene may encode a cytokine receptor, an adhesion molecule, or a complement regulatory protein.

Compositions and methods are provided for modifying and treating neuroinflammatory and neurodegenerative diseases. The methods and compositions can be used to ameliorate the effects of a deficiency in the LC3-associated endocytosis (LANDO) pathway for clearing β-amyloid. Thus, methods are further provided for modulating β-amyloid clearance using an effective amount of a pharmaceutical composition that targets the LANDO pathway. Accordingly, pharmaceutical compositions that target the LANDO pathway are provided herein. The methods and compositions described herein can be used to treat neuroinflammatory and neurodegenerative diseases, such as Alzheimer's disease.

Method for controlling for the appearance of seizures in the mammalian brain comprising modifying the abundance of a specific miRNA-miR-211, for uses in preventing seizures and providing a model system to examine the effect of a drug or a treatment to seizures.

A system is provided comprising a plurality of C. elegans cultures, where each culture comprises a transgenic C. elegans strain that models a mammalian disease or condition. Methods of using a system, e.g., for characterizing microbial strains of a mammalian microbiome and determining whether such microbial strains affect a mammalian disease or disorder.

A method of screening a compound or a composition for use in modulating opioid withdrawal symptoms in a mammal. The method comprises the steps of: selecting a group of test animals; separating the group into two subgroups; inducing Panx1 activation or expression in both subgroups; dosing a first subgroup with a candidate compound; dosing a second subgroup with a placebo; measuring ATP released in spinal microglia of test animals in the first subgroup and in the spinal microglia of test animals in the second subgroup; quantifying the difference in ATP released in spinal microglia of test animals in the first subgroup and in the spinal microglia of test animals in the second subgroup; if the difference in the ATP released in the first subgroup and the APT released in the second subgroup is greater than 25%, then formulating the candidate compound into a pharmaceutical composition.

The present invention relates to an in vitro immune synapse system and a method of in vitro evaluating immune response using the same. The in vitro immune synapse system includes antigen-presenting cells (APCs) and at least one cell type of several specific T cell subtypes isolated from peripheral blood mononuclear cells (PBMCs), all of which is from a same individual of pigs. When a test sample is co-cultured in the in vitro immune synapse system for a given period, it can be determined that the test sample is immunogenic, immunostimulatory or not according to the immunization-related changes of these cells, thereby potentially replacing some kinds of animal experimentation.