Buffering ability of several compounds in vitro, and the effect of a selected buffer combination on ruminal acid production in vivo

Call number: LD2668 .T4 1978 H47Master of Scienc

Global unions: chasing the dream or building the reality?

This article takes as its theme the global restructuring of capital and its impact on worker organization. It argues for a reassertion of class in any analysis of global solidarity, and assesses the opportunities and barriers to effective global unionization. Rooted in the UK experience, the article analyzes the impact of the European social dimension on trade unions, before taking the discussion into a global dimension. It concludes by suggesting that there are reasons for cautious optimism in terms of solidarity building, despite difficult historical legacies and the common replacement of action with rhetoric

Genetic Economy in Picornaviruses: Foot-and-Mouth Disease Virus Replication Exploits Alternative Precursor Cleavage Pathways

The RNA genomes of picornaviruses are translated into single polyproteins which are subsequently cleaved into structural and non-structural protein products. For genetic economy, proteins and processing intermediates have evolved to perform distinct functions. The picornavirus precursor protein, P3, is cleaved to produce membrane-associated 3A, primer peptide 3B, protease 3Cpro and polymerase 3Dpol. Uniquely, foot-and-mouth disease virus (FMDV) encodes three similar copies of 3B (3B1-3), thus providing a convenient natural system to explore the role(s) of 3B in the processing cascade. Using a replicon system, we confirmed by genetic deletion or functional inactivation that each copy of 3B appears to function independently to prime FMDV RNA replication. However, we also show that deletion of 3B3 prevents replication and that this could be reversed by introducing mutations at the C-terminus of 3B2 that restored the natural sequence at the 3B3-3C cleavage site. In vitro translation studies showed that precursors with 3B3 deleted were rapidly cleaved to produce 3CD but that no polymerase, 3Dpol, was detected. Complementation assays, using distinguishable replicons bearing different inactivating mutations, showed that replicons with mutations within 3Dpol could be recovered by 3Dpol derived from “helper” replicons (incorporating inactivation mutations in all three copies of 3B). However, complementation was not observed when the natural 3B-3C cleavage site was altered in the “helper” replicon, again suggesting that a processing abnormality at this position prevented the production of 3Dpol. When mutations affecting polyprotein processing were introduced into an infectious clone, viable viruses were recovered but these had acquired compensatory mutations in the 3B-3C cleavage site. These mutations were shown to restore the wild-type processing characteristics when analysed in an in vitro processing assay. Overall, this study demonstrates a dual functional role of the small primer peptide 3B3, further highlighting how picornaviruses increase genetic economy

BCL-2 family protein expression and platinum drug resistance in ovarian carcinoma

The expression of the BCL-2 family proteins, BCL-2, BAX, BCLXLand BAK have been determined in a panel of 12 human ovarian carcinoma cell lines encompassing a wide range in sensitivity to cisplatin. Whereas BAX, BCLXLand BAK levels did not correlate with sensitivity, there was a statistically significant inverse correlation (r = –0.81;P = 0.002) between growth inhibition by cisplatin and BCL-2 levels. In sublines possessing acquired resistance to various platinum-based drugs or across a panel of human ovarian carcinoma xenografts, there was no consistent pattern of BCL-2 expression. Two relatively sensitive lines (A2780 and CH1) have been stably transfected with bcl-2 and bclXLrespectively and two relatively resistant lines (A2780cisR and SKOV-3) stably transfected with bax. Overexpression of BCL-2 in A2780 cells led to resistance to cisplatin compared to the vector control when assayed at 48 h post-drug incubation but a significant increase in sensitivity at 96 h. Relative rates of apoptosis at 48- and 96-h post-cisplatin exposure mirrored the growth inhibition. There was no significant difference in sensitivity of the pair of lines by clonogenic assay. No significant changes in chemosensitivity to a variety of DNA-damaging or tubulin-interactive agents were observed in the remaining transfected lines. Taken together, these results suggest that, in human ovarian carcinoma cells, high BCL-2 levels (either naturally occurring or through gene transfection) confers a trend towards sensitivity not resistance to platinum drugs. © 2000 Cancer Research Campaig

Dynamics in the murine norovirus capsid revealed by high-resolution cryo-EM

Icosahedral viral capsids must undergo conformational rearrangements to coordinate essential processes during the viral life cycle. Capturing such conformational flexibility has been technically challenging yet could be key for developing rational therapeutic agents to combat infections. Noroviruses are nonenveloped, icosahedral viruses of global importance to human health. They are a common cause of acute gastroenteritis, yet no vaccines or specific antiviral agents are available. Here, we use genetics and cryo-electron microscopy (cryo-EM) to study the high-resolution solution structures of murine norovirus as a model for human viruses. By comparing our 3 structures (at 2.9- to 3.1-Å resolution), we show that whilst there is little change to the shell domain of the capsid, the radiating protruding domains are flexible, adopting distinct states both independently and synchronously. In doing so, the capsids sample a range of conformational space, with implications for maintaining virion stability and infectivity

Involvement of a Nonstructural Protein in Poliovirus Capsid Assembly

Virus capsid proteins must perform a number of roles. These include the ability to self–assemble and to maintain stability under challenging environmental conditions, while retaining the conformational flexibility necessary to uncoat and deliver the viral genome into a host cell. Fulfilling these roles could place conflicting constraints on the innate abilities encoded within the protein sequences. In a previous study, we identified a number of mutations within the capsid coding sequence of poliovirus (PV) that were established in the population during selection for greater thermostability by sequential treatment at progressively higher temperatures. Two mutations in the VP1 protein acquired at an early stage were maintained throughout this selection procedure. One of these mutations prevented virion assembly when introduced into a wild type (wt) infectious clone. Here, we show by sequencing beyond the capsid coding region of the heat selected virions, that two mutations had arisen within the coding region for the 2A protease. Both mutations were maintained throughout the selection process. Introduction of these mutations into a wt infectious clone by site-directed mutagenesis considerably reduced replication. However, they permitted a low level of assembly of infectious virions containing the otherwise lethal mutation in VP1. The 2Apro mutations were further shown to slow the kinetics of viral polyprotein processing and we suggest that this delay improves the correct folding of the mutant capsid precursor protein to permit virion assembly

Scale in education research: towards a multi-scale methodology

This article explores some theoretical and methodological problems concerned with scale in education research through a critique of a recent mixed-method project. The project was framed by scale metaphors drawn from the physical and earth sciences and I consider how recent thinking around scale, for example in ecosystems and human geography might offer helpful points and angles of view on the challenges of thinking spatially in education research. Working between the spatial metaphors of ecology scholars and the critiques of the human geographers, for example the hypercomplex social space in Lefebvre’s political-economic thinking and the fluid, simultaneous, multiple spatialities of Massey’s post-structuralism, I problematize space and scale in education research. Interweaving these geographical ideas with Giddens’ structuration and Bourdieu’s theory of practice, both of which employed what might be termed scale-bridging to challenge social science’s entrenched paradigms, leads me to reconsider what is possible and desirable in the study of education systems. Following the spatial turn in the social sciences generally, there is an outstanding need to theorise multi-scale methodology for education research

Disability activism and the politics of scale

In this paper, we examine the role of spatial scale in mediating and shaping political struggles between disabled people and the state. Specifically, we draw on recent theoretical developments concerning the social construction of spatial scale to interpret two case studies of disability activism within Canada and Ireland. In particular, we provide an analysis of how successful the disability movement in each locale has been at 'jumping scale' and enacting change, as well as examining what the consequences of such scaling-up have been for the movement itself. We demonstrate that the political structures operating in each country markedly affect the scaled nature of disability issues and the effectiveness of political mobilization at different scales

Determination of total I and 129

Total iodine and129-iodine in rivers and lakes of Argentina were measured by means of inductively coupled plasma mass spectrometry and accelerator mass spectrometry respectively. The obtained isotopic ratios, higher than the natural level, are explained as the delayed signal from nuclear weapon atmospheric tests. Besides, deposition fluences in catchment areas of the lakes are analyzed. Their latitudinal dependence, similar to the dependence of annual precipitation rates, favours wet deposition as the main 129I fallout mechanism for this region