Pragmatic pluralism—An explication

The focus with which the paper is concerned is the process or task of intervention and, more specifically, the exploration of three (overlapping and interacting) questions pertinent to those who would intervene:

What is to be done?

How shall we decide what to do?

What can guide our actions?

In terms of what we will describe as pragmatic pluralism (our response to these questions), we intend this to be read in several different ways and on several different levels. Illustrating the discussion with examples from a number of different case studies, we will talk about pluralism in each of the following features:

in the use of specific methods/techniques

in the role(s) of the interventionists

in the modes of representation employed

in the use of different rationalities

in the ‘nature’ of the client

     

Association of the jets of Enceladus with the warmest regions on its south-polar fractures

Jets of material have been seen emanating from the south-polar terrain of Saturn's satellite Enceladus. Observations have shown that this region is anomalously warm, with the hottest measured temperatures coinciding with the four 'tiger stripe' fractures, named Alexandria, Cairo, Baghdad and Damascus, that straddle the region. Here we use Cassini images taken from a variety of viewing directions over two years to triangulate the source locations for the most prominent jets, and compare these with the infrared hotspot locations and the predictions from a recent model of tidally induced shear heating within the fractures. We find that the jets emanate from the four tiger stripes, with the strongest sources on Baghdad and Damascus. All the jets from each fracture seem to lie in the same nearly vertical plane. There is a strong spatial coincidence between our geographical sources and the locations of increased temperature revealed by the infrared experiment. Comparison with the shear heating model shows broad agreement; the exception is the prediction that Baghdad is the least active lineament, whereas we find it to be the most active. We predict that several new hotspots remain to be discovered by future thermal observations.     

Structural definition of a conserved neutralization epitope on HIV-1 gp120

The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 A resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.     

A draft genome of Yersinia pestis from victims of the Black Death

Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348-1350. Genetic architecture and phylogenetic analysis indicate that the ancient organism is ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347-1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.