102 research outputs found

    B-cell receptor-driven MALT1 activity regulates MYC signaling in mantle cell lymphoma.

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    Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of B-cell receptor (BCR) signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 complex that links BCR signaling to the NF-κB pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls an MYC-driven gene expression network predominantly through increasing MYC protein stability. Thus, our analyses identify a previously unappreciated regulatory mechanism of MYC expression. Investigating primary mouse splenocytes, we could demonstrate that MALT1-induced MYC regulation is not restricted to MCL, but represents a common mechanism. MYC itself is pivotal for MCL survival because its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL models. Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy of targeting the MALT1-MYC axis in MCL patients

    Boundary work: An interpretive ethnographic perspective on negotiating and leveraging cross-cultural identity

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    The complexity of global organizations highlights the importance of members’ ability to span diverse boundaries that may be defined by organization structures, national borders, and/or a variety of cultures associated with organization, nation-based societal and work cultures, industries, and/or professions. Based on ethnographic research in a Japan–US binational firm, the paper describes and analyzes the boundary role performance of the firm\u27s Japanese members. It contributes toward theory on boundary spanning by introducing a “cultural identity negotiation” conceptual framework. We show boundary spanning as a process shaped through the interplay of the contextual issues that make a boundary problematic; an individual\u27s multiple repertoires of cultural knowledge; and the individual boundary spanner\u27s “negotiation”, through interaction with others, of his/her cultural identities – the sense of “who I am” as a cultural being that is fundamental to an individual\u27s self-concept. At the same time, we make transparent the epistemological and methodological foundations of an interpretive ethnographic approach, demonstrating its value for understanding complex organizational processes. Research findings have practical implications for the selection and training of an organization\u27s employees, particularly of persons who may be considered “bicultural”

    Economics education and value change: The role of program-normative homogeneity and peer influence

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    In the light of corporate scandals and the recent financial crisis, there has been an increased interest in the impact of business education on the value orientations of graduates. Yet our understanding of how students' values change during their time at business school is limited. In this study,weinvestigate the effects of variations in the normative orientations of economics programs. We argue that interaction among economics students constitutes a key mechanism of value socialization, the effects of which are likely to vary across more-or-less normatively homogeneous economics programs. In normatively homogeneous programs, students are particularly likely to adopt economics values as a result of peer interaction. We specifically explore changes in power, hedonism, and self-direction values in a 2-year longitudinal study of economics students (N 5 197) in a normatively homogeneous and two normatively heterogeneous economics programs. As expected, for students in a normatively homogeneous economics program, interaction with peers was linked with an increase in power and hedonism values, and a decrease in self-direction values. Our findings highlight the interplay between program normative homogeneity and peer interaction as an important factor in value socialization during economics education and have important practical implications for business school leaders

    Line by line : English through grammar stories

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    this book is designed to provide meaningful, relevant, and enjoyable reading practice while offering a clear, intensive focus on specific aspect on English grammar.xii, 188 p.: ill.; 24 cm
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