Histories of molecules: Reconciling the past

Molecular data and methods have become centrally important to evolutionary analysis, largely because they have enabled global phylogenetic reconstructions of the relationships between organisms in the tree of life. Often, however, molecular stories conflict dramatically with morphology-based histories of lineages. The evolutionary origin of animal groups provides one such case. In other instances, different molecular analyses have so far proved irreconcilable. The ancient and major divergence of eukaryotes from prokaryotic ancestors is an example of this sort of problem. Efforts to overcome these conflicts highlight the role models play in phylogenetic reconstruction. One crucial model is the molecular clock; another is that of ‘simple-to-complex’ modification. I will examine animal and eukaryote evolution against a backdrop of increasing methodological sophistication in molecular phylogeny, and conclude with some reflections on the nature of historical science in the molecular era of phylogeny.     

Microbes,mathematics, and models

Microbial model systems have a long history of fruitful use in fields that include evolution and ecology. In order to develop further insight into modelling practice, we examine how the competitive exclusion and coexistence of competing species have been modelled mathematically and materially over the course of a long research history. In particular, we investigate how microbial models of these dynamics interact with mathematical or computational models of the same phenomena. Our cases illuminate the ways in which microbial systems and equations work as models, and what happens when they generate inconsistent findings about shared targets. We reveal an iterative strategy of comparative modelling in different media, and suggest reasons why microbial models have a special degree of epistemic tractability in multimodel inquiry.     

The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria

Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis.     

Performance Management for Social Enterprises

All organisations face the challenge of how to assess performance beyond current financial metrics. These challenges are felt especially strongly by social enterprises, organisations that use business methods to achieve social goals. Social enterprises need to evidence superior social outcomes, are normally accountable to a complex range of stakeholders and yet are often rated low to medium in terms of organisational capacity—thus whilst they have a great need for rounded measurement, they may in practice lack the ability to make use of the different approaches on offer. This paper examines the current and potential use of the conventional Balanced Scorecard model, by social enterprises. The Adventure Capital Fund provides case study evidence of extensive use of a modified Scorecard. The model used is dynamic, combining reflection on the organisation’s current position, ‘near term’ and long term issues. It aims to take a holistic and coherent view of the management of social enterprises. Experience to date suggests that the medium term snapshot provided by the Scorecard is the most valuable, allowing organisations and especially boards and senior executives to keep a ‘strategic grip’ in a period of rapid change and focus on those actions that have best chance of changing performance in the round.     

X-linked inheritance of Fanconi anemia complementation group B

Fanconi anemia is an autosomal recessive syndrome characterized by diverse clinical symptoms, hypersensitivity to DNA crosslinking agents, chromosomal instability and susceptibility to cancer. Fanconi anemia has at least 11 complementation groups (A, B, C, D1, D2, E, F, G, I, J, L); the genes mutated in 8 of these have been identified. The gene BRCA2 was suggested to underlie complementation group B, but the evidence is inconclusive. Here we show that the protein defective in individuals with Fanconi anemia belonging to complementation group B is an essential component of the nuclear protein 'core complex' responsible for monoubiquitination of FANCD2, a key event in the DNA-damage response pathway associated with Fanconi anemia and BRCA. Unexpectedly, the gene encoding this protein, FANCB, is localized at Xp22.31 and subject to X-chromosome inactivation. X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B. Its presence as a single active copy and essentiality for a functional Fanconi anemia-BRCA pathway make FANCB a potentially vulnerable component of the cellular machinery that maintains genomic integrity.     

Functional identification of an aggression locus in the mouse hypothalamus

Electrical stimulation of certain hypothalamic regions in cats and rodents can elicit attack behaviour, but the exact location of relevant cells within these regions, their requirement for naturally occurring aggression and their relationship to mating circuits have not been clear. Genetic methods for neural circuit manipulation in mice provide a potentially powerful approach to this problem, but brain-stimulation-evoked aggression has never been demonstrated in this species. Here we show that optogenetic, but not electrical, stimulation of neurons in the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) causes male mice to attack both females and inanimate objects, as well as males. Pharmacogenetic silencing of VMHvl reversibly inhibits inter-male aggression. Immediate early gene analysis and single unit recordings from VMHvl during social interactions reveal overlapping but distinct neuronal subpopulations involved in fighting and mating. Neurons activated during attack are inhibited during mating, suggesting a potential neural substrate for competition between these opponent social behaviours.     

Under Pressure: Visioning in a Regulated Environment

This paper describes four case studies of the practice of vision development in four utilities organisations. Important observations emerge about current practice; for example, tensions can be observed in organisations struggling to satisfy the expectations of a diverse range of stakeholders. Formal methodologies for visioning are rarely adopted in vision development; rather more informal processes of debate are preferred. Difficulties with internal communication and staff buy-in to the vision are also identified. Comparisons are drawn with the results of previous work on visioning in the financial services sector.     

Atlantic overturning responses to Late Pleistocene climate forcings

The factors driving glacial changes in ocean overturning circulation are not well understood. On the basis of a comparison of 20 climate variables over the past four glacial cycles, the SPECMAP project proposed that summer insolation at high northern latitudes (that is, Milankovitch forcing) drives the same sequence of ocean circulation and other climate responses over 100-kyr eccentricity cycles, 41-kyr obliquity cycles and 23-kyr precession cycles. SPECMAP analysed the circulation response at only a few sites in the Atlantic Ocean, however, and the phase of circulation response has been shown to vary by site and orbital band. Here we test the SPECMAP hypothesis by measuring the phase of orbital responses in benthic delta(13)C (a proxy indicator of ocean nutrient content) at 24 sites throughout the Atlantic over the past 425 kyr. On the basis of delta(13)C responses at 3,000-4,010 m water depth, we find that maxima in Milankovitch forcing are associated with greater mid-depth overturning in the obliquity band but less overturning in the precession band. This suggests that Atlantic overturning is strongly sensitive to factors beyond ice volume and summer insolation at high northern latitudes. A better understanding of these processes could lead to improvements in model estimates of overturning rates, which range from a 40 per cent increase to a 40 per cent decrease at the Last Glacial Maximum and a 10-50 per cent decrease over the next 140 yr in response to projected increases in atmospheric CO(2) (ref. 4).