The Abelson Murine Leukemia Virus (A-MuLV) encodes v-Abl, an oncogenic form of the ubiquitous cellular non-receptor tyrosine kinase, c-Abl. A-MuLV specifically transforms murine B cell precursors both in vivo and in vitro. Inhibition of v-Abl by addition of the small molecule inhibitor STI-571 causes these cells to arrest in the G1 phase of the cell cycle prior to undergoing apoptosis. We found that inhibition of v-Abl activity results in upregulation of transcription of the pro-apoptotic TNF-family ligand TRAIL (tumor-necrosis factor-related apoptosis-inducing ligand). Similarly to BCR-Abl-transformed human cells, activation of the transcription factor Foxo3a led to increased TRAIL transcription and induction of a G1 arrest in the absence of v-Abl inhibition, and this effect could be inhibited by the expression of a constitutively active AKT mutant. Multiple pathways act to inhibit FoxO3a activity within Abelson cells. In addition to diminishing transcription factor activity via inhibitory phosphorylation by AKT family members, we found that inhibition of IKKβ activity results in an increase in the total protein level of FoxO3a. Furthermore over-expression of the p65 subunit of NF-κB results in an increase in TRAIL transcription and in apoptosis and deletion of IKKα and β diminishes TRAIL expression and induction. We conclude that in Abelson cells, the inhibition of both NF-κB and FoxO3a activity is required for suppression of TRAIL transcription and maintenance of the transformed state.Constitutively active forms of the ubiquitous protein tyrosine kinase c-Abl are associated with oncogenic transformation in both mouse and man. In humans, a chromosomal translocation results in fusion of the Breakage Cluster Region (BCR) and c-Abl loci resulting in the production of a BCR-Abl fusion protein that is present in nearly 95% of chronic myelogenous leukemia (CML) and about 10% of acute lymphocytic leukemia
The purpose of this research is to gain a better understanding of expected ethics of audience behavior during a classical music performance. Through a better understanding of cultural identities and practices of the classical music audience, symphony organizations may be able to more closely align audience expectations and the socialization frameworks that are present throughout the classical music experience. The researchers engaged in an ethnographic qualitative research approach in this study. Specific to this study, the researchers were engaging in gaining a greater understanding of classical music audience culture and how this may be impacting participants that are of a “marginalized” or nontraditional classical music audience group. There were 6 new-to-file ticket-buying patrons from the Chattanooga Symphony & Opera who participated in the study. The predominant theme that emerged from the focus group participants was that they like the traditional classical music experience, including venue, audience behavior expectation, and orchestration components, as it is. Further research is needed to better understand if these preferences root in long-standing structural and institutional frameworks that perpetuate cultural identities and practices and minimize audience “performance anxiety” because of reassurance of learned socialization processes (Jacobs, 2000; Mandeles, 1993). Or, if the American classical music audience of today authentically desires the concert etiquette and rituals that began in the 19th century European concert halls because the etiquette and rituals provide an ideal psychological setting for enjoyment of the classical music experience.
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