Comparative analysis of the genome sequences of Bordetella pertussis,Bordetella parapertussis and Bordetella bronchiseptica

Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica are closely related Gram-negative beta-proteobacteria that colonize the respiratory tracts of mammals. B. pertussis is a strict human pathogen of recent evolutionary origin and is the primary etiologic agent of whooping cough. B. parapertussis can also cause whooping cough, and B. bronchiseptica causes chronic respiratory infections in a wide range of animals. We sequenced the genomes of B. bronchiseptica RB50 (5,338,400 bp; 5,007 predicted genes), B. parapertussis 12822 (4,773,551 bp; 4,404 genes) and B. pertussis Tohama I (4,086,186 bp; 3,816 genes). Our analysis indicates that B. parapertussis and B. pertussis are independent derivatives of B. bronchiseptica-like ancestors. During the evolution of these two host-restricted species there was large-scale gene loss and inactivation; host adaptation seems to be a consequence of loss, not gain, of function, and differences in virulence may be related to loss of regulatory or control functions.     

Hybridization between a rare and introduced Oenothera along the north Pacific Coast

Interspecific hybridization has increasingly become regarded as a serious threat to the genetic integrity and persistence of rare plants. Oenothera glazioviana (Onagraceae) is a horticultural species that has escaped cultivation and now threatens the narrow Pacific coastal endemic O. wolfii with hybridization. Reports of morphologically intermediate and ecologically aggressive forms prompted this investigation into the extent of hybridization over the range of O. wolfii . In particular, this study identifies populations of pure and hybrid origins. We used multivariate methods to characterize the morphological variation of Oregon and northern California coastal Oenothera populations. Putatively pure O. wolfii and O. glazioviana individuals do not overlap in many floral characteristics. We found morphologies ranging between the 2 species in northern California populations, however, supporting the inference of hybridization. Remote O. wolfii populations in Oregon were smaller in almost all characters, and discriminant analysis was able to distinguish the rare species from both hybrids and O. glazioviana . However, 5 of 10 O. wolfii populations overlapped significantly with hybrid populations for individual traits and composite morphology, and trait values outside the range of O. wolfii were discovered in 2 populations previously considered to be pure. We also discuss the morphological evidence in light of these species’ chromosomal complexes and environmental factors.     

Biodiversity and biogeography of phages in modern stromatolites and thrombolites

Viruses, and more particularly phages (viruses that infect bacteria), represent one of the most abundant living entities in aquatic and terrestrial environments. The biogeography of phages has only recently been investigated and so far reveals a cosmopolitan distribution of phage genetic material (or genotypes). Here we address this cosmopolitan distribution through the analysis of phage communities in modern microbialites, the living representatives of one of the most ancient life forms on Earth. On the basis of a comparative metagenomic analysis of viral communities associated with marine (Highborne Cay, Bahamas) and freshwater (Pozas Azules II and Rio Mesquites, Mexico) microbialites, we show that some phage genotypes are geographically restricted. The high percentage of unknown sequences recovered from the three metagenomes (>97%), the low percentage similarities with sequences from other environmental viral (n = 42) and microbial (n = 36) metagenomes, and the absence of viral genotypes shared among microbialites indicate that viruses are genetically unique in these environments. Identifiable sequences in the Highborne Cay metagenome were dominated by single-stranded DNA microphages that were not detected in any other samples examined, including sea water, fresh water, sediment, terrestrial, extreme, metazoan-associated and marine microbial mats. Finally, a marine signature was present in the phage community of the Pozas Azules II microbialites, even though this environment has not been in contact with the ocean for tens of millions of years. Taken together, these results prove that viruses in modern microbialites display biogeographical variability and suggest that they may be derived from an ancient community.     

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.     

Strong effect of dispersal network structure on ecological dynamics

A central question in ecology with great importance for management, conservation and biological control is how changing connectivity affects the persistence and dynamics of interacting species. Researchers in many disciplines have used large systems of coupled oscillators to model the behaviour of a diverse array of fluctuating systems in nature. In the well-studied regime of weak coupling, synchronization is favoured by increases in coupling strength and large-scale network structures (for example 'small worlds') that produce short cuts and clustering. Here we show that, by contrast, randomizing the structure of dispersal networks in a model of predators and prey tends to favour asynchrony and prolonged transient dynamics, with resulting effects on the amplitudes of population fluctuations. Our results focus on synchronization and dynamics of clusters in models, and on timescales, more appropriate for ecology, namely smaller systems with strong interactions outside the weak-coupling regime, rather than the better-studied cases of large, weakly coupled systems. In these smaller systems, the dynamics of transients and the effects of changes in connectivity can be well understood using a set of methods including numerical reconstructions of phase dynamics, examinations of cluster formation and the consideration of important aspects of cyclic dynamics, such as amplitude.     

TLR signalling augments macrophage bactericidal activity through mitochondrial ROS

Reactive oxygen species (ROS) are essential components of the innate immune response against intracellular bacteria and it is thought that professional phagocytes generate ROS primarily via the phagosomal NADPH oxidase machinery. However, recent studies have suggested that mitochondrial ROS (mROS) also contribute to mouse macrophage bactericidal activity, although the mechanisms linking innate immune signalling to mitochondria for mROS generation remain unclear. Here we demonstrate that engagement of a subset of Toll-like receptors (TLR1, TLR2 and TLR4) results in the recruitment of mitochondria to macrophage phagosomes and augments mROS production. This response involves translocation of a TLR signalling adaptor, tumour necrosis factor receptor-associated factor 6 (TRAF6), to mitochondria, where it engages the protein ECSIT (evolutionarily conserved signalling intermediate in Toll pathways), which is implicated in mitochondrial respiratory chain assembly. Interaction with TRAF6 leads to ECSIT ubiquitination and enrichment at the mitochondrial periphery, resulting in increased mitochondrial and cellular ROS generation. ECSIT- and TRAF6-depleted macrophages have decreased levels of TLR-induced ROS and are significantly impaired in their ability to kill intracellular bacteria. Additionally, reducing macrophage mROS levels by expressing catalase in mitochondria results in defective bacterial killing, confirming the role of mROS in bactericidal activity. These results reveal a novel pathway linking innate immune signalling to mitochondria, implicate mROS as an important component of antibacterial responses and further establish mitochondria as hubs for innate immune signalling.     

Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus

The influenza pandemic of 1918-19 was responsible for about 50 million deaths worldwide. Modern histopathological analysis of autopsy samples from human influenza cases from 1918 revealed significant damage to the lungs with acute, focal bronchitis and alveolitis associated with massive pulmonary oedema, haemorrhage and rapid destruction of the respiratory epithelium. The contribution of the host immune response leading to this severe pathology remains largely unknown. Here we show, in a comprehensive analysis of the global host response induced by the 1918 influenza virus, that mice infected with the reconstructed 1918 influenza virus displayed an increased and accelerated activation of host immune response genes associated with severe pulmonary pathology. We found that mice infected with a virus containing all eight genes from the pandemic virus showed marked activation of pro-inflammatory and cell-death pathways by 24 h after infection that remained unabated until death on day 5. This was in contrast with smaller host immune responses as measured at the genomic level, accompanied by less severe disease pathology and delays in death in mice infected with influenza viruses containing only subsets of 1918 genes. The results indicate a cooperative interaction between the 1918 influenza genes and show that study of the virulence of the 1918 influenza virus requires the use of the fully reconstructed virus. With recent concerns about the introduction of highly pathogenic avian influenza viruses into humans and their potential to cause a worldwide pandemic with disastrous health and economic consequences, a comprehensive understanding of the global host response to the 1918 virus is crucial. Moreover, understanding the contribution of host immune responses to virulent influenza virus infections is an important starting point for the identification of prognostic indicators and the development of novel antiviral therapies.