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Oncogenic mutations in the serine/threonine kinase B-RAF (also known as BRAF) are found in 50-70% of malignant melanomas. Pre-clinical studies have demonstrated that the B-RAF(V600E) mutation predicts a dependency on the mitogen-activated protein kinase (MAPK) signalling cascade in melanoma-an observation that has been validated by the success of RAF and(More)
Cell-cell fusion is critical to the normal development of certain tissues, yet the nature and degree of conservation of the underlying molecular components remains largely unknown. Here we show that the two guanine-nucleotide exchange factors Brag2 and Dock180 have evolutionarily conserved functions in the fusion of mammalian myoblasts. Their effects on(More)
BACKGROUND Ankyrin 3 (ANK3) has been strongly implicated as a risk gene for bipolar disorder (BD) by recent genome-wide association studies of patient populations. However, the genetic variants of ANK3 contributing to BD risk and their pathological function are unknown. METHODS To gain insight into the potential disease relevance of ANK3, we examined the(More)
An understanding of nuclear reprogramming is fundamental to the use of cells in regenerative medicine. Due to technological obstacles, the time course and extent of reprogramming of cells following fusion has not been assessed to date. Here, we show that hundreds of genes are activated or repressed within hours of fusion of human keratinocytes and mouse(More)
Functional characterization of the human genome requires tools for systematically modulating gene expression in both loss-of-function and gain-of-function experiments. We describe the production of a sequence-confirmed, clonal collection of over 16,100 human open-reading frames (ORFs) encoded in a versatile Gateway vector system. Using this ORFeome(More)
An expression system for rapid and standardized production of human recombinant immunoglobulin Fab fragments in E. coli was developed. Functional folding of the Fab fragments was accomplished by the dicistronic expression vector pFab.gammakappa containing specialized leader sequences to direct the immunoglobulin heavy and light chains to the periplasmic(More)
We describe a Toxoplasma gondii strain that will permit the use of site-specific recombination to study the host-parasite interactions of this organism. This Toxoplasma strain efficiently injects a Cre fusion protein into host cells. In a Cre-reporter cell line, a single parasite invasion induced Cre-mediated recombination in 95% of infected host cells. By(More)
The differentiation of effector CD8(+) T cells is critical for the development of protective responses to pathogens and for effective vaccines. In the first few hours after activation, naive CD8(+) T cells initiate a transcriptional program that leads to the formation of effector and memory T cells, but the regulation of this process is poorly understood.(More)
Growth-Suppressive ORFs inhibition Diff ti l Differential Viability Normalized to Positive Control (MEK1 DD) Resistance ORFs Ranking Supplemental Fig.1: Schematic outlining an ORF-based functional screen for kinases that drive resistance to B-RAF inhibition. The B-RAF V600E cell line A375 was lentivirally transduced with the 597 kinases in the CCSB/Broad(More)
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