The developmental cell biology of Trypanosoma brucei

Trypanosoma brucei provides an excellent system for studies of many aspects of cell biology, including cell structure and morphology, organelle positioning, cell division and protein trafficking. However, the trypanosome has a complex life cycle in which it must adapt either to the mammalian bloodstream or to different compartments within the tsetse fly. These differentiation events require stage-specific changes to basic cell biological processes and reflect responses to environmental stimuli and programmed differentiation events that must occur within a single cell. The organization of cell structure is fundamental to the trypanosome throughout its life cycle. Modulations of the overall cell morphology and positioning of the specialized mitochondrial genome, flagellum and associated basal body provide the classical descriptions of the different life cycle stages of the parasite. The dependency relationships that govern these morphological changes are now beginning to be understood and their molecular basis identified. The overall picture emerging is of a highly organized cell in which the rules established for cell division and morphogenesis in organisms such as yeast and mammalian cells do not necessarily apply. Therefore, understanding the developmental cell biology of the African trypanosome is providing insight into both fundamentally conserved and fundamentally different aspects of the organization of the eukaryotic cell

A High Precision, Optical Polarimeter to Measure Inclinations of High Mass X-Ray Binaries

We present commissioning data for the POLISH instrument obtained on the Hale 5-m telescope. The goal of this high precision polarimeter is to constrain orbital inclination of high mass X-ray binaries and to therefore obtain independent mass estimates for their black hole companions. We have obtained photon shot noise limited precision on standard stars, and we have measured the polarization of bright stars at the part per million level on a nightly basis. Systematic effects have been reduced to less than 1% of the measured polarization for polarized sources and to the part per million level for weakly polarized sources. The high sensitivity of this instrument to asymmetry suggests that valuable contributions will be made in many other fields, including studies of extrasolar planets, debris disks, and stellar astrophysics.Comment: 35 pages, 10 figures, accepted for publication in PAS

The Economic Consequences of the Doha Round for Ireland

This paper provides a quantitative study of the economic effects of a stylised simulation of trade liberalisation for Ireland using the GTAP model. The experiment incorporates the liberalisation of agricultural, manufacturing and services trade as well as measures to improve trade facilitation. The simulation is implemented against a baseline projection of the Irish and world economy over the next decade. Overall, Ireland’s welfare will increase as a result of further trade liberalisation, with particularly strong gains from services liberalisation. The industrial liberalisation scenario also generates positive gains to Ireland, while agricultural liberalisation has a slightly negative effect on the overall economy.

The Economic Consequences of the Doha Round for Ireland

This paper provides a quantitative study of the economic effects of a stylised simulation of trade liberalisation for Ireland using the GTAP model. The experiment incorporates the liberalisation of agricultural, manufacturing and services trade as well as measures to improve trade facilitation. The simulation is implemented against a baseline projection of the Irish and world economy over the next decade. Overall, Ireland's welfare will increase as a result of further trade liberalisation, with particularly strong gains from services liberalisation. The industrial liberalisation scenario also generates positive gains to Ireland, while agricultural liberalisation has a slightly negative effect on the overall economy.Note: Ireland, trade liberalisation, WTO Doha Round

The Doha Development Agenda: Mixed Prospects for Developing Countries

This paper uses the GTAP computable general equilibrium model to assess the impact of a Doha Development Agenda agreement on agricultural trade liberalisation. In particular, we examine the consequences for developing countries. The simulation incorporates further liberalisation in the areas of market access, export competition and domestic support. Most developing regions can expect strong positive results from this liberalisation, however some suffer a decrease in welfare. The magnitude of the welfare effect for these countries depends on measures to be taken by developing countries themselves, and whether they will materialise must be uncertain. The results highlight the importance of the impact of further liberalisation of the erosion of preferential trading arrangements enjoyed by developing regions.Agricultural trade liberalisation, GTAP, developing countries

Disruption of the developmental programme of Trypanosoma brucei by genetic ablation of TbZFP1, a differentiation-enriched CCCH protein

The regulation of differentiation is particularly important in microbial eukaryotes that inhabit multiple environments. The parasite Trypanosoma brucei is an extreme example of this, requiring exquisite gene regulation during transmission from mammals to the tsetse fly vector. Unusually, trypanosomes rely almost exclusively on post-transcriptional mechanisms for regulated gene expression. Hence, RNA binding proteins are potentially of great significance in controlling stage-regulated processes. We have previously identified TbZFP1 as a trypanosome molecule transiently enriched during differentiation to tsetse midgut procyclic forms. This small protein (101 amino acids) contains the unusual CCCH zinc finger, an RNA binding motif. Here, we show that genetic ablation of TbZFP1 compromises repositioning of the mitochondrial genome, a specific event in the strictly regulated differentiation programme. Despite this, other events that occur both before and after this remain intact. Significantly, this phenotype correlates with the TbZFP1 expression profile during differentiation. This is the first genetic disruption of a developmental regulator in T. brucei. It demonstrates that programmed events in parasite development can be uncoupled at the molecular level. It also further supports the importance of CCCH proteins in key aspects of trypanosome cell function

Limitation of Trypanosoma brucei parasitaemia results from a combination of density-dependent parasite differentiation and parasite killing by the host immune response

In the bloodstream of its mammalian host, the "slender" form of Trypanosoma brucei replicates extracellularly, producing a parasitaemia. At high density, the level of parasitaemia is limited at a sublethal level by differentiation to the non-replicative "stumpy" form and by the host immune response. Here, we derive continuous time equations to model the time-course, cell types and level of trypanosome parasitaemia, and compare the best fits with experimental data. The best fits that were obtained favour a model in which both density-dependent trypanosome differentiation and host immune response have a role in limiting the increase of parasites, much poorer fits being obtained when differentiation and immune response are considered independently of one another. Best fits also favour a model in which the slender-to-stumpy differentiation progresses in a manner that is essentially independent of the cell cycle. Finally, these models also make the prediction that the density-dependent trypanosome differentiation mechanism can give rise to oscillations in parasitaemia level. These oscillations are independent of the immune system and are not due to antigenic variation

Implications of Domestic Support Disciplines for Further Agricultural Trade Liberalization

This paper employs the GTAP computable general equilibrium model and dataset to analyse the implications of domestic support reductions in the context of agricultural trade liberalisation. Three specific issues are addressed: overhang in domestic support, the accurate distinction of the boxes in the GTAP dataset and the treatment of market price support in the amber box. An extensive domestic support database is used to calculate the change in applied domestic support rates from a specified cut in bound rates, and to identify the impact on the different domestic support boxes and the required reductions in each support category. The GTAP model is extended to incorporate an explicit representation of the market price support element of the AMS. The results from these extensions of the standard database and model support the view that the impact of an agreement to reduce domestic support will be limited and lower than conventionally estimated. Results of simulations combining domestic support cuts with market access and export competition disciplines show that the effect of import tariff reductions dominate the gains from domestic support cuts once full account is taken of the issues addressed in this paper.WTO agricultural negotiations, domestic support, agricultural protection, Aggregate Measure of Support