Iron Uptake and Homeostasis in Microorganisms

Preface. Iron is considered to be a minor element employed, in a variety of forms, by nearly all living organisms. In some cases, it is utilised in large quantities, for instance for the formation of magnetosomes within magnetotactic bacteria or during use of iron as a respiratory donor or acceptor by iron oxidising or reducing bacteria. However, in most cases the role of iron is restricted to its use as a cofactor or prosthetic group assisting the biological activity of many different types of protein. The key metabolic processes that are dependent on iron as a cofactor are numerous; they include respiration, light harvesting, nitrogen fixation, the Krebs cycle, redox stress resistance, amino acid synthesis and oxygen transport. Indeed, it is clear that Life in its current form would be impossible in the absence of iron. One of the main reasons for the reliance of Life upon this metal is the ability of iron to exist in multiple redox states, in particular the relatively stable ferrous (Fe2+) and ferric (Fe3+) forms. The availability of these stable oxidation states allows iron to engage in redox reactions over a wide range of midpoint potentials, depending on the coordination environment, making it an extremely adaptable mediator of electron exchange processes. Iron is also one of the most common elements within the Earth’s crust (5% abundance) and thus is considered to have been readily available when Life evolved on our early, anaerobic planet. However, as oxygen accumulated (the ‘Great oxidation event’) within the atmosphere some 2.4 billion years ago, and as the oceans became less acidic, the iron within primordial oceans was converted from its soluble reduced form to its weakly-soluble oxidised ferric form, which precipitated (~1.8 billion years ago) to form the ‘banded iron formations’ (BIFs) observed today in Precambrian sedimentary rocks around the world. These BIFs provide a geological record marking a transition point away from the ancient anaerobic world towards modern aerobic Earth. They also indicate a period over which the bio-availability of iron shifted from abundance to limitation, a condition that extends to the modern day. Thus, it is considered likely that the vast majority of extant organisms face the common problem of securing sufficient iron from their environment – a problem that Life on Earth has had to cope with for some 2 billion years. This struggle for iron is exemplified by the competition for this metal amongst co-habiting microorganisms who resort to stealing (pirating) each others iron supplies! The reliance of micro-organisms upon iron can be disadvantageous to them, and to our innate immune system it represents a chink in the microbial armour, offering an opportunity that can be exploited to ward off pathogenic invaders. In order to infect body tissues and cause disease, pathogens must secure all their iron from the host. To fight such infections, the host specifically withdraws available iron through the action of various iron depleting processes (e.g. the release of lactoferrin and lipocalin-2) – this represents an important strategy in our defence against disease. However, pathogens are frequently able to deploy iron acquisition systems that target host iron sources such as transferrin, lactoferrin and hemoproteins, and thus counteract the iron-withdrawal approaches of the host. Inactivation of such host-targeting iron-uptake systems often attenuates the pathogenicity of the invading microbe, illustrating the importance of ‘the battle for iron’ in the infection process. The role of iron sequestration systems in facilitating microbial infections has been a major driving force in research aimed at unravelling the complexities of microbial iron transport processes. But also, the intricacy of such systems offers a challenge that stimulates the curiosity. One such challenge is to understand how balanced levels of free iron within the cytosol are achieved in a way that avoids toxicity whilst providing sufficient levels for metabolic purposes – this is a requirement that all organisms have to meet. Although the systems involved in achieving this balance can be highly variable amongst different microorganisms, the overall strategy is common. On a coarse level, the homeostatic control of cellular iron is maintained through strict control of the uptake, storage and utilisation of available iron, and is co-ordinated by integrated iron-regulatory networks. However, much yet remains to be discovered concerning the fine details of these different iron regulatory processes. As already indicated, perhaps the most difficult task in maintaining iron homeostasis is simply the procurement of sufficient iron from external sources. The importance of this problem is demonstrated by the plethora of distinct iron transporters often found within a single bacterium, each targeting different forms (complex or redox state) of iron or a different environmental condition. Thus, microbes devote considerable cellular resource to securing iron from their surroundings, reflecting how successful acquisition of iron can be crucial in the competition for survival. The aim of this book is provide the reader with an overview of iron transport processes within a range of microorganisms and to provide an indication of how microbial iron levels are controlled. This aim is promoted through the inclusion of expert reviews on several well studied examples that illustrate the current state of play concerning our comprehension of how iron is translocated into the bacterial (or fungal) cell and how iron homeostasis is controlled within microbes. The first two chapters (1-2) consider the general properties of microbial iron-chelating compounds (known as ‘siderophores’), and the mechanisms used by bacteria to acquire haem and utilise it as an iron source. The following twelve chapters (3-14) focus on specific types of microorganism that are of key interest, covering both an array of pathogens for humans, animals and plants (e.g. species of Bordetella, Shigella, , Erwinia, Vibrio, Aeromonas, Francisella, Campylobacter and Staphylococci, and EHEC) as well as a number of prominent non-pathogens (e.g. the rhizobia, E. coli K-12, Bacteroides spp., cyanobacteria, Bacillus spp. and yeasts). The chapters relay the common themes in microbial iron uptake approaches (e.g. the use of siderophores, TonB-dependent transporters, and ABC transport systems), but also highlight many distinctions (such as use of different types iron regulator and the impact of the presence/absence of a cell wall) in the strategies employed. We hope that those both within and outside the field will find this book useful, stimulating and interesting. We intend that it will provide a source for reference that will assist relevant researchers and provide an entry point for those initiating their studies within this subject. Finally, it is important that we acknowledge and thank wholeheartedly the many contributors who have provided the 14 excellent chapters from which this book is composed. Without their considerable efforts, this book, and the understanding that it relays, would not have been possible. Simon C Andrews and Pierre Cornelis

“Financial alchemy” or a zero sum game? Real estate finance, securitisation and the UK property market

Following the US model, the UK has seen considerable innovation in the funding, finance and procurement of real estate in the last decade. In the growing CMBS market asset backed securitisations have included $2.25billion secured on the Broadgate office development and issues secured on Canary Wharf and the Trafford Centre regional mall. Major occupiers (retailer Sainsbury’s, retail bank Abbey National) have engaged in innovative sale & leaseback and outsourcing schemes. Strong claims are made concerning the benefits of such schemes – e.g. British Land were reported to have reduced their weighted cost of debt by 150bp as a result of the Broadgate issue. The paper reports preliminary findings from a project funded by the Corporation of London and the RICS Research Foundation examining a number of innovative schemes to identify, within a formal finance framework, sources of added value and hidden costs. The analysis indicates that many of the gains claimed conceal costs – in terms of market value of debt or flexibility of management – while others result from unusual firm or market conditions (for example utilising the UK long lease and the unusual shape of the yield curve). Nonetheless, there are real gains resulting from the innovations, reflecting arbitrage and institutional constraints in the direct (private) real estate market

Military doctrine, command philosophy and the generation of fighting power: genesis and theory

Military doctrine is one of the conceptual components of war. Its raison d’être is that of a force multiplier. It enables a smaller force to take on and defeat a larger force in battle. This article’s departure point is the aphorism of Sir Julian Corbett, who described doctrine as ‘the soul of warfare’. The second dimension to creating a force multiplier effect is forging doctrine with an appropriate command philosophy. The challenge for commanders is how, in unique circumstances, to formulate, disseminate and apply an appropriate doctrine and combine it with a relevant command philosophy. This can only be achieved by policy-makers and senior commanders successfully answering the Clausewitzian question: what kind of conflict are they involved in? Once an answer has been provided, a synthesis of these two factors can be developed and applied. Doctrine has implications for all three levels of war. Tactically, doctrine does two things: first, it helps to create a tempo of operations; second, it develops a transitory quality that will produce operational effect, and ultimately facilitate the pursuit of strategic objectives. Its function is to provide both training and instruction. At the operational level instruction and understanding are critical functions. Third, at the strategic level it provides understanding and direction. Using John Gooch’s six components of doctrine, it will be argued that there is a lacunae in the theory of doctrine as these components can manifest themselves in very different ways at the three levels of war. They can in turn affect the transitory quality of tactical operations. Doctrine is pivotal to success in war. Without doctrine and the appropriate command philosophy military operations cannot be successfully concluded against an active and determined foe.

‘Scripture its own interpreter’: Mary Martha Sherwood, the Bible and female autobiography

This is a reading of the work of Mary Martha Sherwood, the Victorian Evangelist and Children’s Author (and pupil at the Abbey School, Reading). Based upon research on Sherwood’s private correspondences and diary conducted at UCLA with the aid of a Mitzi Myers (this before my arrival at Reading), the essay offers a radical reinterpretation of her work. Previously understood in terms of a rigid, if self-contradictory and ‘anxious’, Evangelism, the essay reads the diary through Sherwood’s little known Biblical scholarship. Through this I argue that Sherwood grants her own writing the status of Biblical truth precisely because of its contradictions and ‘anxiety’.

A Real-time, Predictive Architecture for Distributed Virtual Reality

User interaction within a virtual environment may take various forms: a teleconferencing application will require users to speak to each other (Geak, 1993), with computer supported co-operative working; an Engineer may wish to pass an object to another user for examination; in a battle field simulation (McDonough, 1992), users might exchange fire. In all cases it is necessary for the actions of one user to be presented to the others sufficiently quickly to allow realistic interaction. In this paper we take a fresh look at the approach of virtual reality operating systems by tackling the underlying issues of creating real-time multi-user environments.

Issues and benefits of using 3D Interfaces: visual and verbal tasks

Spatial memory is important for locating objects in hierarchical data structures, such as desktop folders. There are, however, some contradictions in literature concerning the effectiveness of 3D user interfaces when compared to their 2D counterparts. This paper uses a task-based approach in order to investigate the effectiveness of adding a third dimension to specific user tasks, i.e. the impact of depth on navigation in a 3D file manager. Results highlight issues and benefits of using 3D interfaces for visual and verbal tasks, and introduces the possible existence of a correlation between aptitude scores achieved on the Guilford- Zimmerman Orientation Survey and Electroencephalography- measured brainwave activity as participants search for targets of variable perceptual salience in 2D and 3D environments.

Designing a questionnaire to gather carer input to pain assessment for hospitalized people with dementia

We describe development of a questionnaire to elicit pain symptoms and experience, for use by people with dementia or their carers, at hospital admission. The questionnaire provided contextual information to support professionals’ use of the Abbey Pain Scale, a validated tool used by nursing staff internationally. Appropriate information and physical design were required in order, not only to create an approachable questionnaire for patients and carers, but also to ensure fit with hospital processes. Fit with hospital process had significant influence on the final form of the questionnaire, compromising some aspects of design for patients and carers, but this compromise was considered essential to ensure pain management procedures were supplemented by wider, contextual information.

British television drama: past, present and future. 2nd edition

British Television Drama provides resources for critical thinking about key aspects of television drama in Britain since 1960, including institutional, textual, cultural, economic and audience-centred modes of study. It presents and contests significant strands of critical work in the field, and comprises essays by TV professionals and academics plus editors' introductions to each section that contextualise the chapters. The new edition includes a revised chapter by acclaimed TV producer Tony Garnett reflecting on his work since Cathy Come Home in the 1960s, new chapters by Phil Redmond, the creator of Brookside and Hollyoaks, and Cameron Roach, Head of Drama Commissioning at Sky TV and former executive producer of Waterloo Road. New academic analyses include work on Downton Abbey, The Sarah Jane Adventures, Ashes to Ashes, adaptations of Persuasion, and the changing production methods on Coronation Street.

L’illustration marginale d’un ouvrage profane : étude du manuscrit Paris, Bibliothèque nationale de France, français 95, xiiie siècle (1290)

BnF fr. 95 is a late 13th century manuscript containing Arthurian romances and other fictional and didactic texts. The Estoire del saint Graal and Merlin section is the most highly illuminated, with a rich marginal iconography, an unusual feature in the illustration of lay works and in these texts’ manuscript tradition. This article shows how in Merlin and its Vulgate Sequel marginal scenes overlap with widespread subjects in courtly and chivalric vernacular romances, in contrast with Latin and religious works. The reuse of similar patterns in principal and marginal miniatures, examined in the episode of the Battle of Danablaise, where King Arthur fights the Saxon King Rion, highlights the need for a comprehensive reading of text and images, taking into account the mise en page and the different levels of illustration in the manuscript.

The Coronation mantle and the Westminster sanctuary pavement

The Great Sanctuary pavement at Westminster Abbey, on which the kings of England were crowned, features a design of rotated squares, around a central roundel of unusual Egyptian alabaster, set within a circle of bright blue glass. The roundel’s visual resemblance to the world and the firmament is underlined by a surrounding inscription, identifying it as the world, the macrocosm. This paper proposes that the design and meaning of the Great Sanctuary pavement reflect the square macrocosmic mantle in which the English king was wrapped during the coronation ceremony. This paper underlines the special nature of the English coronation mantle within the context of other royal and imperial cosmic mantles. Its square form was unique, and it featured in the English coronation liturgies in a way that European mantles did not. The English liturgies stressed its role as a representation of the world or macrocosm

Thyroid hormones regulate anxiety in the male mouse

Thyroid hormone levels are implicated in mood disorders in the adult human but the mechanisms remain unclear partly because, in rodent models, more attention has been paid to the consequences of perinatal hypo and hyperthyroidism. Thyroid hormones act via the thyroid hormone receptor (TR) alpha and beta isoforms, both of which are expressed in the limbic system. TR's modulate gene expression via both unliganded and liganded actions. Though the thyroid hormone receptor (TR) knockouts and a transgenic TRalpha1 knock-in mouse have provided us valuable insight into behavioral phenotypes such as anxiety and depression, it is not clear if this is because of the loss of unliganded actions or liganded actions of the receptor or due to locomotor deficits. We used a hypothyroid mouse model and supplementation with tri-iodothyronine (T3) or thyroxine (T4) to investigate the consequences of dysthyroid hormone levels on behaviors that denote anxiety. Our data from the open field and the light-dark transition tests suggest that adult onset hypothyroidism in male mice produces a mild anxiogenic effect that is possibly due to unliganded receptor actions. T3 or T4 supplementation reverses this phenotype and euthyroid animals show anxiety that is intermediate between the hypothyroid and thyroid hormone supplemented groups. In addition, T3 but not T4 supplemented animals have lower spine density in the CA1 region of the hippocampus and in the central amygdala suggesting that T3-mediated rescue of the hypothyroid state might be due to lower neuronal excitability in the limbic circuit.

Självet, rollerna och pågående koordinationer av mänskliga handlingar : Om att försöka se ’samhället’ som något annat än fängelse eller marionetteater

The self, roles and the ongoing coordination of human action. Trying to see ‘society’ as neither prison nor puppet theatre In the article it is argued that structural North-American role-sociology may be integrated with theories emphasizing ‘society’ as ongoing processes (f. ex. Giddens’ theory of structuration). This is possible if the concept of role is defined as a recurrence oriented to the action of others standing out as a regularity in a societal process. But this definition makes it necessary to in a fundamental way understand what kind of social being the role-actor is. This is done with the help of Hans Joas’ theory of creativity and Merleau-Pontys concept of ‘flesh’ arguing that Meads concept of the ‘I’ maybe understood as an embodied self-asserting I, which at least in reflexive modernity has the creative power to split Meads ‘me’ into a self-voiced subject-me and an other voiced object-me. The embodied I communicating with the subject-me may be viewed as that role-actor which is something else than the role played. But this kind of role-actor is making for new troubles because it is hard to understand how this kind of self is creating self-coherence by using Meads concept of ‘the generalized other’. This trouble is handled by using Alain Touraines concept of the ‘subject’ and arguing that the generalized other is dissolving in de-modernized modernity. In split modernity self-coherence may instead be created by what in the article is called the generalized subject. This concept means a kind of communicative future based evaluation, which has its base in the ‘subject’ opposing the split powers of both the instrumentality of markets and of life-worlds trying to create ‘fundamentalistic’ self-identities. This kind of self is communicative because it also must respect the other as ‘subject’. It exists only in the battle against the forces of the market or a community. It never constructs an ideal city or a higher type of individual. It creates and protects a clearing that is constantly being invaded, to use the words of the old Frenchman himself. Asa kind of test-case it is by the way in the article shown how Becks concept of individualization may be understood in a deeply social and role-sociological way.