25 research outputs found
Management Accounting Aspects 4: MAA114
No full textExamination on Management Accounting Aspects 4: MAA114, Nov 201
Management Accounting Aspects 4 : MAA 4114
No full textExamination on Management Accounting Aspects 4 :MAA 4114, Jan 201
Neuroimmune regulation of JCV by immune mediators in glial cells
No full text2012 - 2013The human polyomavirus JC (JCV) is a small DNA virus responsible for the initiation of progressive multifocal leukoencephalopathy (PML), an often lethal disease of the brain characterized by lytic infection of oligodendrocytes in the central nervous system (CNS). Patients undergoing immune modulatory therapies for the treatment of autoimmune diseases such as multiple sclerosis, and individuals with an impaired-immune system, most notably AIDS patients, are in the high risk group of developing PML. Previous studies suggested that soluble immune mediators secreted from PBMCs inhibited viral genomic replication. However little is known regarding the molecular mechanism of this regulation. Here we investigated the impact of conditioned media (CM) from activated PBMCs on viral replication and gene expression by molecular virology techniques. Our data showed that viral gene expression as well as viral replication was suppressed by the CM. Further studies revealed that soluble immune mediators from PBMCs possessed a dual control on T-antigen expression at transcription and post-transcription level. These observations demonstrate a novel role of immune mediators in regulation of JCV gene expression, and provide a new avenue of research to understand molecular mechanism of viral reactivation in patients who are at risk of developing PML. [edited by author]XII n.s
High expression of MeCP2 in JC virus-infected cells of progressive multifocal leukoencephalopathy brains
No full textMutations of the methyl CpG binding protein 2 (MeCP2) gene are a major cause of Rett syndrome. To investigate whether the expression of this gene was related to JC virus (JCV) infection, we examined brains of four progressive multifocal leukoencephalopathy (PML) patients. JCV infection was confirmed by immunohistochemical labeling with antibodies against JCV VP1, Agnoprotein and large T antigen. MeCP2 expression was examined by immunohistochemistry using a specific polyclonal antibody against MeCP2. In normal brains and uninfected cortices of PML brains, MeCP2 expression was observed in the nuclei of neurons, but not observed in glial and endothelial cell nuclei. In PML brains, however, intense immunolabeling was observed in abnormally enlarged glial nuclei of JCV-infected cells. Double immunolabeling using antibodies against large T antigen (visualized as blue) and MeCP2 (visualised as red) revealed purple JCV infected nuclei, which confirmed that the JCV infected nuclei expressed MeCP2. We conclude that MeCP2 is highly expressed in the JCV infected nuclei of PML brain and these results may provide a new insight into the mechanism which regulates the MeCP2 expression in glial cells by the infection of JCV
Progressive multifocal leukoencephalopathy with mild clinical conditions and detection of archetype-like JC virus in cerebrospinal fluid
No full textProgressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system with a poor prognosis and is primarily caused by JC virus (JCV) with a mutation called prototype. We encountered a case of PML with moderate progression and analyzed the mutational patterns of JCV in the cerebrospinal fluid (CSF). A 19-year-old Japanese woman with mild neurological symptoms was diagnosed with combined immunodeficiency following pneumocystis pneumonia. Brain magnetic resonance imaging scan showed multiple brain lesions, and real-time polymerase chain reaction testing detected JCV in the CSF, leading to the diagnosis of PML. The disease course of PML was stable after administration of mefloquine and mirtazapine with immunoglobulin replacement therapy. In the JCV genome cloned from the patient CSF, DNA sequences of the gene encoding the capsid protein (VP1) and the non-coding control region exhibited small mutations. However, they were quite similar to those of the archetype JCV, which persists asymptomatically in healthy individuals. These findings provide insight into the mutational characteristics of JCV in PML with mild symptoms and progression
JC human polyomavirus is associated to chromosomal instability in peripheral blood lymphocytes of Hodgkin's lymphoma patients and poor clinical outcome
No full textInternational audienceBackground: B cells are potential sites for latency and reactivation of the human neurotropic JC polyomavirus (JCV). We investigated JCV and Epstein-Barr virus (EBV) status in peripheral blood lymphocytes (PBL) from 74 Hodgkin's lymphoma (HL) and 91 B-cell non-Hodgkin's lymphoma (B-NHL) patients. Patients and methods: JCV and EBV DNA were assessed by PCR, and FISH technique was used to localize viral infection and to estimate chromosomal instability (rogue cells, 'chromosomal aberrations') throughout evolution. The influence of viral infection and chromosomal instability on freedom from progression (FFP) was investigated in HL patients. Results: PCR product sequencing of PBL identified JCV in 42 (57%) circulating lymphocytes of HL patients. FISH analysis revealed that the presence of cells with a high JCV genome copy number-associated to the presence of rogue cells and 'higher frequency of chromosomal aberrations'-increased from 15% before treatment to 52% (P < 10-5) after. The co-activation of JCV and EBV was independent of known prognostic parameters and associated with a shorter FFP (JCV and EBV co-activation P < 0.001, rogue cells P < 0.002). Conclusion: In HL, JCV activation and chromosomal instability have been identified in PBL and associated with a poorer prognosis, especially in EBV+. © The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected]
Viroporin activity of the JC polyomavirus is regulated by interactions with the adaptor protein complex 3
No full textViroporins, which are encoded by a wide range of animal viruses, oligomerize in host cell membranes and form hydrophilic pores that can disrupt a number of physiological properties of the cell. Little is known about the relationship between host cell proteins and viroporin activity. The human JC polyomavirus (JCV) is the causative agent of progressive multifocal leukoencephalopathy. The JCV-encoded agnoprotein, which is essential for viral replication, has been shown to act as a viroporin. Here we demonstrate that the JCV agnoprotein specifically interacts with adaptor protein complex 3 through its delta subunit. This interaction interrupts adaptor protein complex 3-mediated vesicular trafficking with suppression of the targeting of the protein to the lysosomal degradation pathway and instead permits the transport of agnoprotein to the cell surface with resulting membrane permeabilization. The findings demonstrate a previously undescribed paradigm in virus-host interactions allowing the host to regulate viroporin activity and suggest that the viroporins of other viruses may also be highly regulated by specific interactions with host cell proteins
Neil Diamond: A Personal Educational Appreciation of an Excellent Artist’s Live Performances
No full textIn this article the performances of the singer Neil Diamond in South Africa are studied to enable the author, a lecturer at a South African university, to learn from Diamond how to develop on professional level. Since the singer announced in 2018 that he would, because of a diagnosis of Parkinson’s disease, no longer be performing live, the study was conducted in reflection on his performing career, which stretched over more than four decades, and the effect that it has had on the lecturer’s professional development. Embedded in the theory of transformative learning, the methodology that was used, namely the 5D framework of appreciative inquiry, was selected because it provided the scaffolding for the reflective research process. After conducting interviews with six people who attended one of Diamond’s performances, five themes were identified and are presented and discussed in this paper: the interaction between Diamond and his audiences; keeping up with the latest technology; Diamond’s enjoyment of what he did and his enthusiasm about his performances; his neat black clothes and professional appearance; and his passionate immersion in those performances. To capture the essence of Diamond’s performances, the author wrote a poem and painted a painting to represent what he learned from Diamond. The effect that his engagement with Diamond has had on the technology and decoration in his lecture hall is also explained
Resisting Assimilation to the Melting Pot
No full textThe melting pot metaphor suggest that people from different backgrounds come to the United States and through the process of assimilation adapt to a new lifestyle integrating smoothly into the dominant culture. This article argues that immigrants from diverse cultural and ethnic groups that try to keep some of their cultural traditions may encounter conflict when trying to adapt to their life in the new context. The author contends for a cultural curriculum of the home endorsing family cultural values and traditions tha is overlooked by schools and educators, disregarding its potential for enhancing children’s learning process and academic achievement
Parallel Oppressions
No full textSchooling is generally a culture, a context, where there are particular behaviors that are allowable and those that are not. What we allow, recommend, and encourage for both our students and teachers says a great deal about what our society believes about freedom, empowerment, politics, and controversy. This article shares a theoretical view of the authoritarian school structure and its impact on both students and teachers. While this is a primarily theoretical piece, the author also shares examples from current research that paint a picture of the unfortunate teacher-society and teacher-student interactions, but also the potential for meaningful human engagement
