Abstract: Acute exposure to estrogenic chemicals is shown herein to induce DNA damage mediated by formation of ER?-dependent R-loops. Disclosed herein are methods for evaluating the safety and activity of a xenoestrogen. Also disclosed are methods for identifying subject particularly susceptible to the genotoxic effects of endogenous estrogens or environmental xenoestrogens. This method can be used to select suitable hormone therapies, such as a selective estrogen receptor modulator (SERM), aromatase inhibitor, or selective estrogen receptor degrader (SERD).

Abstract: The invention is based on the discovery of biomarkers and gene signatures that are useful for determining the presence of atypical hyperplasia in a breast lesion, and for determining whether a pre-malignant breast lesion is likely to progress to breast cancer. In particular, the present invention provides methods and reagents for detecting and profiling the expression levels of these biomarkers and genes, and methods of using the expression profiles for predicting the likelihood that a pre-malignant lesion will progress to breast cancer.

Abstract: Methods and cell lines for cloning ungulate embryos and offspring, in particular bovines and porcines, are provided. The resultant fetuses, embryos or offspring are especially useful for the expression of desired heterologous DNAs, and may be used as a source of cells or tissue for transplantation therapy for the treatment of diseases such as Parkinson's disease.

Abstract: Methods and cell lines for cloning ungulate embryos and offspring, in particular bovines and porcines, are provided. The resultant fetuses, embryos or offspring are especially useful for the expression of desired heterologous DNAs, and may be used as a source of cells or tissue for transplantation therapy for the treatment of diseases such as Parkinson's disease.

Abstract: A culture system for maintaining avian PGCs for long periods in tissue culture is provided. This culture system uses LIF, bFGF, IGF-I and SCF. The resultant PGCs are useful for the production of transgenic and chimeric avians, in particular, chickens or turkeys.

Abstract: Methods and cell lines for cloning ungulate embryos and offspring, in particular bovines and porcines, are provided. The resultant fetuses, embryos or offspring are especially useful for the expression of desired heterologous DNAs, and may be used as a source of cells or tissue for transplantation therapy for the treatment of diseases such as Parkinson's disease.

Abstract: A culture system for producing PGCs or EG cells by culturing PGCs for long periods in tissue culture is provided. This culture system uses LIF, bFGF, IGF and SCF. The resultant EG cells are useful for the production of transgenic and chimeric avians, in particular, chickens and turkeys, and also for cloning purposes.

Abstract: An improved method of nuclear transfer involving the transplantation of donor differentiated cell nuclei into enucleated oocytes of the same species as the donor cell is provided. The resultant nuclear transfer units are useful for multiplication of genotypes and transgenic genotypes by the production of fetuses and offspring, and for production of isogenic CICM cells, including human isogenic embryonic or stem cells. Production of genetically engineered or transgenic mammalian embryos, fetuses and offspring is facilitated by the present method since the differentiated cell source of the donor nuclei can be genetically modified and clonally propagated.

Abstract: An improved method of nuclear transfer involving the transplantation of donor differentiated cell nuclei into enucleated oocytes of the same species as the donor cell is provided. The resultant nuclear transfer units are useful for multiplication of genotypes and transgenic genotypes by the production of fetuses and offspring, and for production of isogenic CICM cells, including human isogenic embryonic or stem cells. Production of genetically engineered or transgenic mammalian embryos, fetuses and offspring is facilitated by the present method since the differentiated cell source of the donor nuclei can be genetically modified and clonally propagated.

Abstract: Methods and cell lines for cloning bovine embryos and offspring are provided. The resultant embryos or offspring are especially useful for the expression of desired heterologous DNAs.

Abstract: A culture system for maintaining avian PGCs for long periods in tissue culture is provided. This culture system uses LIF, bFGF, IGF and SCF. The resultant PGCs are useful for the production of transgenic and chimeric avians, in particular, chickens or turkeys.

Abstract: Novel cultured inner cell mass (CICM) cells, and cell lines, derived from ungulates, in particular, pigs and cows, and methods for their preparation are provided. The subject CICMs possess similar morphology and express cell markers identically or substantially similarly to ICMs of undifferentiated developing embryos for prolonged culturing periods. Heterologous DNA is inserted into the subject CICM cells and cell lines so as produce transgenic CICM cell which are introduced into non-human fertilized embryos to produce transgenic chimeric embryos. The transgenic chimeric embryos are transferred into recipient females where they are permitted to develop into transgenic chimeric fetuses. Recipient females give birth to transgenic chimeric animals which are capable of transmitting the heterologous DNA to their progeny. Transgenic CICM cells are also used to produce cloned transgenic embryos, fetuses and offspring.

Abstract: An improved method of nuclear transfer involving the transplantation of donor differentiated cell nuclei into enucleated oocytes of the same species as the donor cell is provided. The resultant nuclear transfer units are useful for multiplication of genotypes and transgenic genotypes by the production of fetuses and offspring, and for production of isogenic CICM cells, including human isogenic embryonic or stem cells. Production of genetically engineered or transgenic mammalian embryos, fetuses and offspring is facilitated by the present method since the differentiated cell source of the donor nuclei can be genetically modified and clonally propagated.