Nineteenth-century commentators often claimed that Russia burned to the ground every thirty years. In an empire whose cities were built of wood, firefighters had a visible presence throughout ...Russia’s urban centres and became politically active across the country. Democracy Burning? studies the political, cultural, and social values of volunteer firefighters and reveals the ways in which their public organizations cooperated with the authoritarian state.
OBJECTIVE: The prevalence of Epstein‐Barr virus (EBV) and the recently discovered Kaposi's sarcoma associated herpes virus, human herpesvirus 8 (KSHV or HHV8), was determined within oral lesions ...common to HIV infection including OHL, pseudoOHL (PHL), oral lymphoma, oral aphthous ulcers, and an oral Kaposi's sarcoma.
METHODS: DNA and RNA were extracted from oral lesions. EBV and HHV8 genomes were detected by Southern blot and polymerase chain reaction (PCR), and viral expression was analyzed using PCR amplification of cDNA.
RESULTS: Multiple EBV strains were detected within OHL with recombination across repeat sequences generating new viral variants. EBV expression in OHL included expression of some viral genes, usually expressed in latent infections, that induce the EBV receptor. EBV replication was detected only within OHL lesions but not within adjacent Kaposi's tissue or oral aphthous ulcers while HHV8 was only detected within the Kaposi's lesions.
CONCLUSIONS: These findings indicate that the OHL lesion is unique with viral replication and superinfection with additional EBV strains. Expression of the EBV receptor within the OHL lesion may promote superinfection which then activates EBV replication. The consistent detection of EBV replication only within OHL lesions and the detection of HHV8 only within Kaposi's sarcoma, strengthens the etiologic link between EBV and HHV8 infection to these specific pathologies.
Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with a variety of malignancies including nasopharyngeal carcinoma. The EBV-encoded latent membrane protein 1 (LMP1) is considered the ...EBV oncogene as it is necessary for EBV-induced B-lymphocyte transformation and has been shown to transform rodent fibroblasts. LMP1 contains two signaling domains, the carboxy-terminal activating region 1 and 2 (CTAR1 and CTAR2), by which NF-kappaB, phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase, and c-Jun N-terminal kinase are activated. In this study, the role of CTAR1 and CTAR2 in LMP1-mediated transformation of rodent fibroblasts was analysed. CTAR1 was found to be necessary for rodent fibroblast transformation, whereas CTAR2 was dispensable. The activation of the PI3K pathway in Rat-1 cells by LMP1 and LMP1-CTAR1 in transformed cells resulted in phosphorylated Akt and phosphorylated glycogen synthase kinase 3beta. The role of PI3K and NF-kappaB activation in LMP1-mediated transformation was further analysed using the chemical inhibitors LY294002 and BAY 11-7085. LY294002 inhibited CTAR1-induced focus formation and anchorage-independent growth, whereas BAY 11-7085 did not inhibit focus formation or anchorage-independent growth. Similar studies in human fibroblasts confirmed that LMP1-CTAR1 also mediates aberrant growth, phosphorylation of Akt, and decreased levels of p27. These findings indicate that LMP1-mediated rodent fibroblast transformation is dependent upon activation of PI3K and Akt and is independent of activation of NF-kappaB.
The sequence of the latent membrane protein 1 (LMP-1) gene was analysed in Epstein-Barr virus (EBV) isolates from specific regions representing both type 1 and type 2 EBV. A predominant strain marked ...by an XhoI restriction enzyme polymorphism (REP) within the LMP-1 gene has been identified in type 1 EBV in nasopharyngeal carcinoma (NPC) from Southern China. This polymorphism was also present in type 2 EBV in NPC from Alaska. In this study, the sequence of the LMP-1 gene was determined in these samples representing type 1 and type 2 EBV and was compared with the prototype lymphoid strains. Consistent nucleotide variation in the amino terminus of LMP-1 was identified in strains marked by the XhoI REP. These changes were present in both EBV type 1 and type 2 strains. Three types of sequence variation were detected in the carboxy terminus of LMP-1. The LMP-1 sequences differed in the number of an 11 amino acid repeat element. In the prototype EBV type 1 (B95-8) sequence and in the type 1 Raji and type 2 HR-1 strains, the third repeat element contained an insertion of 5 amino acids that were also the first five unique amino acids after the last partial repeat element. The third variation was a deletion of amino acids 343 to 352 of the B95-8 LMP-1. This deletion was detected in the type 1 Chinese EBV strains, but was not detected in the type 2 Alaskan strains although the Chinese and Alaskan strains have nearly identical amino acid changes at the amino terminus. Numerous other amino acid changes were detected in the carboxy terminus which did not cosegregate with either EBV type, amino acid changes in the amino terminus, or specific geographic regions. These data indicate that EBV strains can be distinguished by sequence differences within LMP-1 and that unlike the divergence between type 1 and type 2 EBV in Epstein-Barr nuclear antigen sequences, different EBV types are nearly identical in LMP-1 sequence.
This volume brings together some of the best writing published in the journal Management Learning since its re-launch under this title in 1994. The selection very much reflects the mission of the ...journal to act as a showcase for innovative, international and interdisciplinary work which covers a wide gamut of issues connected to management, organizations, learning and knowledge. The field of management learning, widely drawn in this way, brings together some of the key preoccupations within several areas of management, organization studies and social science more generally. Learning and knowledge have become central themes within thee areas for several reasons, both practical and theoretical. These include the way that organizational learning is seen as a key source of competitive advantage, and the wider analysis that individuals and organizations now inhabit a `knowledge economy?. Theoretically, recent years have seen emerging understandings of the social significance of `communities of practice?, whilst learning in its many manifestations is increasingly seen as being imbricated in issues of power. This latter points to one of the particular areas which has been a focus for the journal, namely more critically orientated approaches to management learning. This collection provides readings grouped under six key headings which reflect where some of the most influential and provocative work in the field has been done over recent years, namely: \- Organizational Learning and Learning Organizations \- Individual Learning \- Critical Approaches to Management Education and Learning \- Pedagogical Practice \- Globalization and Management Learning \- Beyond Management Learning Along with an editorial introduction, this volume will provide a unique and invaluable resource for anyone studying or researching management learning and cognate areas, by bringing together some of the best peer-reviewed work in the field.
EBV is associated with the epithelial cancer, nasopharyngeal carcinoma (NPC), and the lymphoid malignancy, Hodgkin lymphoma (HL). The EBV latent membrane proteins 1 and 2A are expressed in these ...tumors. These proteins activate the phosphatidylinositol 3'-OH kinase (PI3K)/Akt pathway, which is commonly activated inappropriately in malignancy. In this study, the status of Akt activation and its targets, glycogen synthase kinase-3beta (GSK-3beta) and beta-catenin, was investigated in NPC and HL clinical specimens. In the majority of HL and NPC specimens, Akt was activated, indicating an important role for this kinase in the development and/or progression of these tumors. Akt phosphorylates and inactivates GSK-3beta, a negative regulator of the proto-oncoprotein beta-catenin that is aberrantly activated in many cancers. GSK-3beta was phosphorylated and inactivated with concomitant nuclear beta-catenin accumulation in the majority of NPC specimens. The malignant cells of the majority of HL cases, however, did not have inactivated GSK-3beta and lacked nuclear beta-catenin expression. These data indicate that this signaling arm of PI3K/Akt is universal and important in NPC pathogenesis but is apparently not affected in HL. These findings point to a divergence in pathways activated by EBV in different cellular contexts.
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