Browsing by Subject "WAC"
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Item Decision Cases For Writing Across the Curriculum(University of Minnesota, 1996-06) Duin, Ann Hill; Simmons, Steve; Lammers, ElizabethWhile case studies have existed in formal business education since the early 20th century, the case method has seen little application to writing-across-the-curriculum (WAC) efforts. The goal of this project was to provide a detailed process for developing and implementing decision cases for WAC efforts as well as data on their effectiveness in a scientific course. College students read decision cases, developed written arguments in support of their decisions, and discussed the cases with high school students via a desktop video-conferencing system. During fall quarter 1992 we studied the decision-case development process by collaborating to complete two new decision cases for use in university and secondary classrooms. We kept detailed notes regarding our design process, and we compared our process to Stolovitch and Keeps' (1991) process. During winter quarter1993, we investigated the use of four decision cases with 25 students in AnPl 3010: Environment and World Food Production. For two of the cases, we did a content analysis of students' concept maps and case responses. For the other two cases, we videotaped the conferences and analyzed them according to Daft and Lengel's (1986) framework for studying media richness theory. We also collected questionnaire data regarding the students' understanding and attitude toward writing, the environment, and decision cases in general as well as the students' attitudes toward discussing the cases with high school students. We learned that constructing decision cases is a complex process involving multiple audiences and disciplines. Students indicated that their knowledge about the environment and agro-ecosystems increased significantly as a result of the course, although they did not necessarily attribute this increase to their work with decision cases and writing. The instructor's expectation for good writing and his comments on students' case responses overlapped with results from Walvoord and McCarthy (1990). Last, the students viewed video-conferencing as a unique opportunity to share information and to learn from younger writers. The central implication from this study is that decision cases can be used as writing-intensive components in scientific courses. Decision cases engage students in an authentic dilemma with a writing task that involves problem solving and structuring coherent arguments.Item Literacy and Minnesota’s Academic Culture: A Case for Institutional Change(University of Minnesota, 2003) Bridwell-Bowles, LillianItem Mapping Function and Cooperativity in the Cancer Genome: RSPO2 and WAC(2014-09) Conboy, CaitlinCancer is a leading cause of morbidity and mortality worldwide. Developing molecularly targeted therapies to improve patient outcomes will require comprehensive understanding of the genetic events that give rise to cancer. Large-scale efforts to catalog the genetic aberrations in human tumors are currently underway. Transposon-based insertional mutagenesis screens provide a complementary, comparative genomics approach for cancer gene discovery. Sleeping Beauty (SB) transposon mutagenesis has been used to identify genes that contribute to intestinal tumor formation. Two of the identified genes, Rspo2 and Wac, were the subjects of this thesis research. R-spondin 2 (RSPO2) belongs to the R-spondin family of secreted Wnt agonists. Activation of RSPO2 and 3 has been identified in human colorectal and liver cancer, although the functional significance of these lesions has not been proven, and genetic screens in mice suggested that Rspo2 and Rspo3 are oncogenic in the mammary gland as well. Here we present an analysis of RSPO2 and 3 in human colon, breast, and liver cancer. We found that expression of RSPO2 and 3 was increased in subsets of all three tumor types, and correlated with activation of Wnt signaling in these tumors compared to normal tissues. We further investigated the functional significance of increased RSPO2 in breast and liver cancer models. We showed that RSPO2 can activate Wnt signaling in non-transformed breast epithelial cells and RSPO2 overexpression is required for Wnt signaling and proliferation in an RSPO2-high breast cancer cell line. We developed an in vivo model of RSPO2 activation in the mouse liver using hydrodynamic tranfection with transposon-based DNA vectors followed by Fah selection. We found that increased expression of RSPO2 in the liver activated Wnt signaling and promoted hepatomegaly. RSPO2 overexpression cooperated with Trp53 inactivation to initiate tumor formation. Hepatocellular carcinomas that formed in this model exhibited activated Wnt signaling. This model will facilitate further studies of R-spondin signaling and enable development of RSPO-targeted therapy. WW domain containing adaptor with coiled-coil (WAC) is an adaptor protein required for diverse biological processes, including regulation of gene transcription through histone H2B monoubiquitination. Wac was inactivated by transposon insertions in three SB screens for genetic drivers of intestinal tumorigenesis in wild type, Apc-deficient, and Trp53-deficient backgrounds. We found that WAC was somatically mutated and downregulated in human colorectal tumors. Further, mutant versions of WAC identified in human tumors were unable to transcriptionally activate expression of cdkn1a (the gene encoding p21) in a zebrafish embryo model. Depletion of Wac cooperated with Apc and Trp53 inactivation to promote anchorage independent growth of mouse colonic epithelial cells. The results of these studies collectively implicate RSPO2 as an oncogene in multiple wnt-responsive tissues and suggest WAC is a tumor suppressor in the colon that cooperates with APC and TP53. Additional work is warranted to further define the signaling pathways regulated by RSPO2 and WAC in tumorigenesis and to determine if drug targeting of these pathways is a viable strategy for improving the treatment of RSPO2 and WAC-driven cancers.