An instrument for fixedly transplanting a living body embryo into a uterus has an instrument, for transplanting the living body embryo into the uterus, which is to be inserted into a uterus and a magnetic embryo accommodation container holding instrument (transferred embryo fixing instrument) to be attached to the living body. The instrument for transplanting the living body embryo into the uterus has an embryo accommodation container having an embryo accommodation part having an embryo insertion portion communicating with outside and a magnetic material and a shaft-shaped container transfer tool for separably holding the embryo accommodation container at its distal end portion. The magnetic container holding instrument has an attaching part to be attached to an epidermis of the living body and a magnet capable of attracting the magnetic material of the embryo accommodation container thereto.

A method of in vitro fertilization wherein the embryo is implanted into the uterus of a female patient at least two, and preferably three to twelve months after the eggs are retrieved from the patient in order to reduce the effect of autoimmune rejection of the embryo by the patient's autoimmune system and increase the probability and success of pregnancy and wherein prior to embryo implantation, the endometrium in the uterus is prepared for embryo implantation by introducing peripheral blood mononuclear cells (PBMCs) into the uterus. The procedure is combined with cryopreservation techniques to preserve the oocytes or the IVF-produced embryos of the patient.

A method of in vitro fertilization wherein the embryo is implanted into the uterus of a female patient at least two, and preferably three to twelve months after the eggs are retrieved from the patient in order to reduce the effect of autoimmune rejection of the embryo by the patient's autoimmune system and increase the probability and success of pregnancy and wherein prior to embryo implantation, the endometrium in the uterus is prepared for embryo implantation by introducing peripheral blood mononuclear cells (PBMCs) into the uterus. The procedure is combined with cryopreservation techniques to preserve the oocytes or the IVF-produced embryos of the patient.

Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

Compositions and methods are provided for making rat pluripotent and totipotent cells, including rat embryonic stem (ES) cells. Compositions and methods for improving efficiency or frequency of germline transmission of genetic modifications in rats are provided. Such methods and compositions comprise an in vitro culture comprising a feeder cell layer and a population of rat ES cells or a rat ES cell line, wherein the in vitro culture conditions maintain pluripotency of the ES cell and comprises a media having mouse leukemia inhibitory factor (LIF) or an active variant or fragment thereof. Various methods of establishing such rat ES cell lines are further provided. Methods of selecting genetically modified rat ES cells are also provided, along with various methods to generate a transgenic rat from the genetically modified rat ES cells provided herein. Various kits and articles of manufacture are further provided.

Compositions and methods are provided for making rat pluripotent and totipotent cells, including rat embryonic stem (ES) cells. Compositions and methods for improving efficiency or frequency of germline transmission of genetic modifications in rats are provided. Such methods and compositions comprise an in vitro culture comprising a feeder cell layer and a population of rat ES cells or a rat ES cell line, wherein the in vitro culture conditions maintain pluripotency of the ES cell and comprises a media having mouse leukemia inhibitory factor (LIF) or an active variant or fragment thereof. Various methods of establishing such rat ES cell lines are further provided. Methods of selecting genetically modified rat ES cells are also provided, along with various methods to generate a transgenic rat from the genetically modified rat ES cells provided herein. Various kits and articles of manufacture are further provided.

Methods and compositions directed to altering a population of sRNAs in a sperm using vesicles isolated from an epididymosome are provided. Methods and compositions directed to altering a population of sRNAs in an oocyte using vesicles isolated from an epididymosome are also provided. Methods for altering an sRNA population in a sperm or an oocyte can be used to prevent, or reduce the severity of, a disease, disorder, or condition that would otherwise be inherited by progeny. For example, certain epigenetic inherited conditions due to paternal effects, such as certain metabolic and stress disorders and conditions, can be ameliorated in progeny using sperm or oocytes having an altered sRNA population.

Methods and compositions directed to altering a population of sRNAs in a sperm using vesicles isolated from an epididymosome are provided. Methods and compositions directed to altering a population of sRNAs in an oocyte using vesicles isolated from an epididymosome are also provided. Methods for altering an sRNA population in a sperm or an oocyte can be used to prevent, or reduce the severity of, a disease, disorder, or condition that would otherwise be inherited by progeny. For example, certain epigenetic inherited conditions due to paternal effects, such as certain metabolic and stress disorders and conditions, can be ameliorated in progeny using sperm or oocytes having an altered sRNA population.

A proximity switch system that includes a self-contained power consuming device and a power source in electrical communication with the power consuming element across a magnetic proximity switch is disclosed. The proximity switch system includes an external magnet removably coupled to the magnetic proximity switch. A method of storing and/or transporting a proximity switch system is also disclosed. The method includes providing the proximity switch system and removably coupling an external magnet to the magnetic proximity switch in a position to prevent the magnetic proximity switch from inadvertently switching on.