Two-component signal transduction in Bacillus cereus and closely related bacteria

Bacillus cereus is a Gram-positive pathogen that is recognised as an important cause of food-borne disease worldwide. Within the genus Bacillus, B. cereus and its closest relatives form a homogeneous subdivision that has been termed the B. cereus group. This group includes B. anthracis, a pathogen that can cause anthrax in mammals, and B. thuringiensis, an insect pathogen that is used as an insecticide worldwide. Members of the B. cereus group can adapt to a wide range of environmental challenges. In bacteria, these challenges are generally monitored by two-component systems (TCS), which consist of a histidine kinase (HK) and a partner response regulator (RR). Upon sensing a specific environmental stimulus, the HK activates its cognate RR, which in turn controls the expression of genes that are involved in the appropriate response. This thesis describes the functional analysis of TCSs in the B. cereus group. By using in silico techniques, 50-58 HKs and 48-52 RRs were identified in eight different B. cereus group genomes. Biological functions, including the involvement in sporulation, biofilm formation and host-microbe interactions were predicted for these TCS proteins. A phylogenetic footprinting approach was developed and used to identify specific binding sites and target genes for over 50% of the B. cereus group DNA-binding RRs. These predictions allowed relating several RRs to a minimal regulon and thereby to a characteristic transcriptional response. To further support these predictions, the transcriptomes of two B. cereus TCS deletion mutants (ΔyvrHG and ΔyufLM) were analysed and compared with the transcriptome of wild-type B. cereus. This revealed that the minimal regulon predictions were correct for the two respective TCSs. Furthermore, the predicted biological roles for these TCSs, including roles in antibiotic resistance (YvrHG) and fumarate metabolism (YufLM), were supported by phenotypic tests. Besides the many “classical” HKs and RRs detected in the B. cereus group, several a-typical TCS proteins were found. These included five RRs without a DNA-binding output domain and two hybrid HKs (HK-RR fusions). Genome analyses revealed that one of the hybrid HK-encoding genes (BC1008) is located in a conserved gene cluster that also encodes the a-typical RR RsbY. In B. cereus, RsbY is known to activate the key stress-responsive sigma factor σB. As a partner HK for RsbY was still “missing”, the role of BC1008 in the σB-mediated stress response was tested. Indeed, a bc1008 deletion strain appeared incapable of inducing σB and its associated regulon upon stress conditions and appeared impaired in its heat adaptive response. In addition, truncation of the BC1008 fused RR receiver domain indicated that this domain plays a role in fine-tuning BC1008 activity. A comparative genome analysis further indicated that BC1008-type hybrid HKs control σB-like sigma factors in at least several other Gram-positive bacteria, including Geobacillus, Paenibacillus and actinobacteria. In summary, the research described in this thesis contributes to our understanding of B. cereus adaptive responses through TCSs. This knowledge may be applied for the development of novel intervention strategies for an improved control of B. cereus in food production environments. <br/

Monotheisme kan uw staat ernstige schade toebrengen

Intro: In 2010 verschenen twee boeken van Paul Cliteur over secularisme, godsdienst (vooral in zijn monotheïstische verschijningsvorm), terrorisme en de publieke zaak; één in het Engels – The Secular Outlook – en één in het Nederlands – Het monotheïstisch dilemma. Het zijn twee zelfstandige boeken. Het Engelse is niet simpelweg een vertaling van het Nederlandse werk. Niettemin is er een grote mate van overlapping. De boeken behandelen soortgelijke thema’s en ontvouwen soortgelijke argumenten, maar richten zich toch op verschillende aspecten van de verhouding tussen kerk en staat, geloof en politiek. The Secular Outlook is vooral een verdediging van de notie dat de publieke ruimte een godsdienstvrije zone moet zijn. Het monotheïstisch dilemma wijst vooral op het geweldspotentieel van godsdienst en doet voorstellen om dat gevaar het hoofd te bieden

Pragmatism and Dynamics: Does Pragmatist Adjustment Go All the Way Down?

Pragmatism has become an established academic topic focused on an accepted canon of works and a number of seminal authors. There is something ironic about this fixation of the Pragmatist tradition. An anticipation of transience and embrace of adaptability runs through many of the classic works of Pragmatism. Nevertheless, there seems to be a tendency to fixate Pragmatism and freeze it in its classic iterations, especially with respect to its philosophy of scientific inquiry. The article seeks to retrieve the dynamics and adaptability the classical Pragmatists built into their notion of scientific inquiry. It seeks to illustrate the need for such flexibility with recent developments in the field of economics. When the financial crisis struck in 2007-2008, this involved more than the insolvency of a number of large banks. The crisis, at the very least, also involved the bankruptcy of a dominant economic model. It raised questions about the rationality of markets and the widespread faith in soft-touch regulation. It cast doubt on decades of neo-classical economic dogma that counseled small government, privatisation, and free markets. Neo-classical economics did not float free from other concerns. It informed notions about the role of the state, the limits of public policy, and the scope of democratic decision-making. Indeed, faith in rational, self-correcting markets affected debates in disparate disciplines like law, political science, philosophy, ethics, and history in many non-trivial ways. Hence, the financial crisis is also a crisis of scientific research

Evaluation of Labeling Strategies for Rotating Maps

We consider the following problem of labeling points in a dynamic map that allows rotation. We are given a set of points in the plane labeled by a set of mutually disjoint labels, where each label is an axis-aligned rectangle attached with one corner to its respective point. We require that each label remains horizontally aligned during the map rotation and our goal is to find a set of mutually non-overlapping active labels for every rotation angle $\alpha \in [0, 2\pi)$ so that the number of active labels over a full map rotation of 2$\pi$ is maximized. We discuss and experimentally evaluate several labeling models that define additional consistency constraints on label activities in order to reduce flickering effects during monotone map rotation. We introduce three heuristic algorithms and compare them experimentally to an existing approximation algorithm and exact solutions obtained from an integer linear program. Our results show that on the one hand low flickering can be achieved at the expense of only a small reduction in the objective value, and that on the other hand the proposed heuristics achieve a high labeling quality significantly faster than the other methods.Comment: 16 pages, extended version of a SEA 2014 pape

Combatting exploitation of migrant temporary agency workers through sectoral self-regulation in the UK and the Netherlands

The recent growth of precarious work has sparked a vivid debate on whether this tendency can be reversed by the social partners through sectoral self-regulation. In this sectoral case study of the temporary work agencies sector in the United Kingdom and the Netherlands, the views, approaches, power and interaction between trade unions and employers’ organizations are studied in the context of increasing labour migration in the decade following European Union enlargement. The results show that the employers’ organizations have been leading actors in self-regulation, seeking collaboration with trade unions in the Netherlands. In both countries, trade unions have taken an inclusive approach but had little power to affect the deterioration of employment conditions. It has proven difficult to the social partners to reverse the process of increasing precarious work and exploitation. Strict regulatory frameworks imposed by the government are needed to turn a vicious circle into a virtuous one

Religion in the 21st Century Debating the Post-Secular Turn

__Abstract__ For a long time there seemed to be a broad consensus in Western democracies - at least among political theorists and legal scholars - concerning the place of religion in the public sphere and the separation of church and state. However, since the end of the last century, religion has again become a highly contentious issue. With the arrival of sizable groups of immigrants for whom religion remains an integral part of their identity - not only Muslims, but also evangelical Christians - religion is back in the public square of many modern Western democracies (a place, arguably, it never really disappeared from in the United States). This reassertion of religion, Stanley Fish observed in 2005, has ‘re-alerted us to the fact […] that hundreds of millions of people in the world do not observe the distinction between the private and the public, or between belief and knowledge, and that it is no longer possible for us to regard such persons as quaintly pre-modern or as needy recipients of our saving (an ironic word) wisdom’. In the same article, Fish predicted that religion was going to be the wave of the future in academics: ‘Announce a lecture or panel on ‘religion in our time’ and you will have to hire a larger hall’. Intrigued by this resurgence of religion - and tempted by a high attendance rate - we hired a larger hall and convened a conference on ‘Religion in the 21st Century’ at the Erasmus School of Law, in September 2011. The focus of this conference was the question: Does the revival of religion confront us with a familiar phenomenon that we can describe and analyse in tried-and-tested categories, or has religious experience transformed into something altogether different, which demands a new approach, a new way of relating to religion? The articles collected in this special issue all originate from this gathering and all, in their own way, try to come to terms with its central theme

Directional gene flow and ecological separation in Yersinia enterocolitica

Yersinia enterocolitica is a common cause of food-borne gastroenteritis worldwide. Recent work defining the phylogeny of the genus Yersinia subdivided Y. enterocolitica into six distinct phylogroups. Here, we provide detailed analyses of the evolutionary processes leading to the emergence of these phylogroups. The dominant phylogroups isolated from human infections, PG3–5, show very little diversity at the sequence level, but do present marked patterns of gain and loss of functions, including those involved in pathogenicity and metabolism, including the acquisition of phylogroup-specific O-antigen loci. We tracked gene flow across the species in the core and accessory genome, and show that the non-pathogenic PG1 strains act as a reservoir for diversity, frequently acting as donors in recombination events. Analysis of the core and accessory genome also suggested that the different Y. enterocolitica phylogroups may be ecologically separated, in contrast to the long-held belief of common shared ecological niches across the Y. enterocolitica species

Crossroads in New media, Identity & Law

__Abstract__ This volume brings together a number of timely contributions at the nexus of new media, politics and law. The central intuition that ties these essays together is that information and communication technology, cultural identity, and legal and political institutions are spheres that co-evolve and interpenetrate in myriad ways. Discussing these shifting relationships, the contributions all probe the question of what shape diversity will take as a result of the changes in the way we communicate and spread information: that is, are we heading to the disintegration and fragmentation of national and cultural identity, or is society moving towards more consolidation, standardization and centralization at a transnational level? In an age of digitization and globalization, this book addresses the question of whether this calls for a new civility fit for the 21st century