67 research outputs found

    Re-localization of Cellular Protein SRp20 during Poliovirus Infection: Bridging a Viral IRES to the Host Cell Translation Apparatus

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    Poliovirus IRES-mediated translation requires the functions of certain canonical as well as non-canonical factors for the recruitment of ribosomes to the viral RNA. The interaction of cellular proteins PCBP2 and SRp20 in extracts from poliovirus-infected cells has been previously described, and these two proteins were shown to function synergistically in viral translation. To further define the mechanism of ribosome recruitment for the initiation of poliovirus IRES-dependent translation, we focused on the role of the interaction between cellular proteins PCBP2 and SRp20. Work described here demonstrates that SRp20 dramatically re-localizes from the nucleus to the cytoplasm of poliovirus-infected neuroblastoma cells during the course of infection. Importantly, SRp20 partially co-localizes with PCBP2 in the cytoplasm of infected cells, corroborating our previous in vitro interaction data. In addition, the data presented implicate the presence of these two proteins in viral translation initiation complexes. We show that in extracts from poliovirus-infected cells, SRp20 is associated with PCBP2 bound to poliovirus RNA, indicating that this interaction occurs on the viral RNA. Finally, we generated a mutated version of SRp20 lacking the RNA recognition motif (SRp20Ξ”RRM) and found that this protein is localized similar to the full length SRp20, and also partially co-localizes with PCBP2 during poliovirus infection. Expression of this mutated version of SRp20 results in a ∼100 fold decrease in virus yield for poliovirus when compared to expression of wild type SRp20, possibly via a dominant negative effect. Taken together, these results are consistent with a model in which SRp20 interacts with PCBP2 bound to the viral RNA, and this interaction functions to recruit ribosomes to the viral RNA in a direct or indirect manner, with the participation of additional protein-protein or protein-RNA interactions

    Radiation Induces Acute Alterations in Neuronal Function

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    Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs) from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABAARs). These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study

    Regulator Vulnerabilities to Political Pressure and Political Tie Intensity: The Moderating Effects of Regulatory and Political Distance

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    This study applies the institution-based view and neo-institutional theory in addressing how managerial perceptions of regulator vulnerabilities to political pressure, and institutional distance, influence intensification of political ties. Our analysis of 181 wholly owned foreign subsidiary (WOFSs) operating in the Philippines suggests that managerial perceptions of regulator vulnerability to political pressures positively enhance the intensification of political ties. Our results also reveal that regulatory distance and, more importantly, the simultaneous presence of political and regulatory distance diminish the positive relationship between managerial perceptions of regulator vulnerability to political pressures and a WOFS’s propensity to enhance the intensification of political ties. Managerial implications and future research directions are discusse

    Perceived managerial and leadership effectiveness in a Korean context: An indigenous qualitative study

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    Multinational corporations (MNCs) across the world have sent an increasing number of managers abroad to leverage unprecedented opportunities in the era of globalization. However, their failure rate has been above 33% for decades, resulting in substantial costs (Puck, Kittler, & Wright, 2008). One of the primary reasons for this failure is a lack of understanding of the national and organizational cultures within the host countries (Festing & Maletzky, 2011). For example, while a number of MNCs have entered the Korean market, several such as Yahoo, Motorola, and Walmart have failed and withdrawn due to the companies’ lack of adjustment to the Korean cultural context (Choe, 2006; Woo, 2013). In spite of the significance of culturally embedded practices, most researchers who have explored management and leadership in Asian countries, whether they were Western or indigenous researchers, have implemented studies using extant Western management and leadership theories derived within the Western cultural context (Leung, 2007; Tsui, 2006). Numerous scholars have claimed that this could be problematic because the findings of such studies may not be applicable to non-Western countries (Li, 2012; Liden & Antonakis, 2009), and may fail to provide insights and understanding of novel contexts or to reveal indigenous aspects of management and leadership (Tsui, 2007). Consequently, there have been increasing calls for indigenous management and leadership research within Asian countries (see Li et al., 2014; Lyles, 2009; Tsui, 2004; Wolfgramm, Spiller, & Voyageur, 2014). Over the past 30 years, managerial effectiveness and leadership effectiveness have been substantially neglected areas of management research (Noordegraaf & Stewart, 2000; Yukl, Gordon, & Taber, 2002). In addition, there has been little agreement on what specific behaviors distinguish effective managers from ineffective ones. Furthermore, more research is needed to examine the managerial and leadership behaviors that are critical for shaping the performance of individuals, groups and organizations (see Borman & Brush, 1993; Cammock, Nilakant & Dakin, 1995; Mumford, 2011; Noordegraaf & Stewart, 2000; Yukl et al., 2002). While most of the research related to managerial and leadership effectiveness has been conducted in the U.S., the few notable non-U.S. studies include that of Cammock et al. (1995) in New Zealand who developed a behavioral lay model of managerial effectiveness using the repertory grid technique. Another notable exception is the cumulative series of perceived managerial and leadership effectiveness studies conducted by Hamlin with various indigenous co-researchers in Western and non-Western countries (see Hamlin & Patel, 2012; Ruiz, Wang, & Hamlin, 2013) using Flanagan’s (1954) critical incident technique (CIT)

    Preparation of Vaccines β€” Cell Substrates

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    Diversity and Top Management Teams

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