Segregation of a microsporidian parasite during host cell mitosis

We investigated the segregation of an intracellular microsporidian parasite during host cell division. A time-course experiment was carried out to examine the distribution of parasites relative to host chromosomal DNA via light and electron microscopy. Fluorescent light microscopy and EM studies showed that the parasite lay in the perinuclear zone of the host cell during interphase and segregated to daughter cells at mitosis. At metaphase, the parasite was frequently closely associated with host microtubules and mitochondria. Electron-dense bridges were observed between the parasites and the host microtubules and also between host mitochondria and microtubules. The study suggests that both the parasite and the host cell organelles segregate in association with spindle microtubules

Cellular distribution of a feminizing microsporidian parasite: a strategy for transovarial transmission

The cellular distribution of a vertically transmitted, feminizing microsporidian was followed in its host Gammarus duebeni. In adult females the parasite was restricted to gonadal tissue, in particular primary and secondary follicle cells. Spores were diplokaryotic with a thin spore wall and a short polar filament, characteristics typical of ‘early’ spores involved in autoinfection. The diplokaryotic life-cycle, absence of spore groupings and of a pansporoblast membrane typify the genus Nosema. However, the unusual globular polaroplast of the spore and restriction of this stage to host ovarian tissue have not previously been described in Nosema. Sporogony occurred only in follicle cells adjacent to developing oocytes and was in synchrony with the process of vitellogenesis. Oocytes were infected after formation of intracellular connections with follicle cells but harboured only vegetative stages of the parasite. Parasites were associated with the perinuclear cytoplasm and, in developing embryos, segregated to daughter cells along the axis of the spindle. In juvenile animals there was no evidence of pathology linked with feminization and the parasite was found at low density in cells under the cuticle. The parasite is highly adapted to transovarial transmission with an efficient mechanism of oocyte infection and no evidence of pathology

INCORPORATING EPIDEMIOLOGICAL PROJECTIONS OF MORBIDITY AND MORTALITY INTO AN OPEN ECONOMY GROWTH MODEL: AIDS IN SOUTH AFRICA

HIV prevalence dynamics are introduced into a three sector, neoclassical growth model. The model is calibrated to South African national accounts data and used to examine the potential impact of HIV/AIDS on economic growth. Projections portend if left unchecked, the long run impact of HIV and AIDS could drive South African GDP to levels that are over 60% less than no-HIV levels, with AIDS death rates decreasing the long run stock of labor by over 60%.Health Economics and Policy,

Structure, substrate recognition and reactivity of Leishmania major mevalonate kinase

This research was supported by the German Academic Exchange Service (DAAD), the Wellcome Trust (TKS and WNH as Trust Senior Research fellows), the Biotechnology and Biological Science Research Council (Structural Proteomics of Rational Targets) and the European Synchrotron Radiation Facility.Background: Isoprenoid precursor synthesis via the mevalonate route in humans and pathogenic trypanosomatids is an important metabolic pathway. There is however, only limited information available on the structure and reactivity of the component enzymes in trypanosomatids. Since isoprenoid biosynthesis is essential for trypanosomatid viability and may provide new targets for therapeutic intervention it is important to characterize the pathway components. Results: Putative mevalonate kinase encoding genes from Leishmania major (LmMK) and Trypanosoma brucei (TbMK) have been cloned, over-expressed in and proteins isolated from procyclic-form T. brucei. A highly sensitive radioactive assay was developed and shows ATP-dependent phosphorylation of mevalonate. Apo and (R)-mevalonate bound crystal structures of LmMK, from a bacterial expression system, have been determined to high resolution providing, for the first time, information concerning binding of mevalonate to an MK. The mevalonate binds in a deep cavity lined by highly conserved residues. His25 is key for binding and for discrimination of (R)-over (S)-mevalonate, with the main chain amide interacting with the C3 hydroxyl group of ( R)mevalonate, and the side chain contributing, together with Val202 and Thr283, to the construction of a hydrophobic binding site for the C3 methyl substituent. The C5 hydroxyl, where phosphorylation occurs, points towards catalytic residues, Lys18 and Asp155. The activity of LmMK was significantly reduced compared to MK from other species and we were unable to obtain ATP-binding data. Comparisons with the rat MK:ATP complex were used to investigate how this substrate might bind. In LmMK, helix alpha 2 and the preceding polypeptide adopt a conformation, not seen in related kinase structures, impeding access to the nucleotide triphosphate binding site suggesting that a conformational rearrangement is required to allow ATP binding. Conclusion: Our new structural information, consistent with data on homologous enzymes allows a detailed description of how mevalonate is recognized and positioned for catalysis in MK. The mevalonate-binding site is highly conserved yet the ATP-binding site is structurally distinct in LmMK. We are unable to provide a definitive explanation for the low activity of recombinant protein isolated from a bacterial expression system compared to material isolated from procyclic-form Trypanosoma brucei.Publisher PDFPeer reviewe

A multi-INT semantic reasoning framework for intelligence analysis support

Lockheed Martin Corp. has funded research to generate a framework and methodology for developing semantic reasoning applications to support the discipline oflntelligence Analysis. This chapter outlines that framework, discusses how it may be used to advance the information sharing and integrated analytic needs of the Intelligence Community, and suggests a system I software architecture for such applications

Contemporaneity in the History of Art: A Clark Workshop 2009, Summaries of Papers and Notes on Discussions

Sponsored by the Clark Institute, Williamstown, and the Getty Research Institute, Los Angeles, the workshop was convened by Terry Smith, and held at the Sterling and Francine Clark Institute, Williamstown, Mass., October 8 and 9, 2009. These notes do not record the exact statements of all participants, neither in the summaries of papers nor notes on discussions; rather, they represent the author’s own impressions of the workshop as it unfolded. See also, in this issue of Contemporaneity, Wu Hung’s contribution to the workshop.</jats:p

Writing the history of Australian art: its past, present and possible future

In the years around 1980 the history of Australian art was reconceived in a bewildering variety of ways. A historiographical revolution was underway. This was largely the result of plethora of new approaches to art history that emerged worldwide during the 1970s: contextual, feminist, populist, Marxist. Aboriginal art awaited detailed art historical consideration. This article places these changes in the context of previous efforts to chart the history of Australian art, which the author argues occurred in six phases: colonial, bourgeois nationalist, realist versus aestheticist, modernist, culturalist, and the approaches noted above. Most of these approaches developed in Australia and were applied by local authors. In recent decades, however, ‘external’ approaches are more evident, and are deeply preoccupied with the question of defining modernism in Australia, which they largely fail to do. The author surveys a number of such attempts, taking this question as the paradoxical key to unraveling the overall structure of the history of Australian art