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

Economic models and algorithms for distributed systems

Distributed computing paradigms for sharing resources such as Clouds, Grids, Peer-to-Peer systems, or voluntary computing are becoming increasingly popular. While there are some success stories such as PlanetLab, OneLab, BOINC, BitTorrent, and SETI@home, a widespread use of these technologies for business applications has not yet been achieved. In a business environment, mechanisms are needed to provide incentives to potential users for participating in such networks. These mechanisms may range from simple non-monetary access rights, monetary payments to specific policies for sharing. Although a few models for a framework have been discussed (in the general area of a "Grid Economy"), none of these models has yet been realised in practice. This book attempts to fill this gap by discussing the reasons for such limited take-up and exploring incentive mechanisms for resource sharing in distributed systems. The purpose of this book is to identify research challenges in successfully using and deploying resource sharing strategies in open-source and commercial distributed systems.

Microprocessor systems: an introduction

The aim of this book is to provide and introduction to microprocessor systems, their operation and design. It covers those topics needed by engineers and computer scientists who are interested in applying microprocessors in practical situations, namely computer hardware including logic and interfacing, software, in particular high level and assembly language programming, and the design and testing of such systems. The fundamental principles of micrprocessor systems are described and these are illustrated with reference to two microprocessors, the 32-bit MC68020 from Motorola and a single chip microcomputer, the 8051 from Intel; and in addition, interfacing to the general purpose STE bus is described. The details of the processors and the bus are concentrated in three chapters, thus allowing the presentation of the material to be independent of the microprocessors if that is desired, and permitting the specific details to be found easily.

Modula-2 applied

Programming is a skill which requires knowledge of both the basic constructs of the computer language used and techniques employing these constructs. How these are used in any given application is determined intuitively, and this intuition is based on experience of programs already written. One aim of this book is to describe the techniques and give practical examples of the techniques in action - to provide some experience. Another aim of the book is to show how a program should be developed, in particular how a relatively large program should be tackled in a structured manner. These aims are accomplished essentially by describing the writing of one large program, a diagram generator package, in which a number of useful programming techniques are employed. Also, the book provides a useful program, with an in-built manual describing not only how the program works, but also how it does it, with full source code listings. This means that the user can, if required, modify the package to meet particular requirements. A floppy disk is available from the publishers containing the program, including listings of the source code. All the programs are written in Modula-2, using JPI's Top Speed Modula-2 system running on IBM-PCs and compatibles. This language was chosen as it is an ideal language for implementing large programs and it is the main language taught in the Cybernetics Department at the University of Reading. There are some aspects of the Top Speed implementation which are not standard, so suitable comments are given when these occur. Although implemented in Modula-2, many of the techniques described here are appropriate to other languages, like Pascal of C, for example. The book and programs are based on a second year undergraduate course taught at Reading to Cybernetics students, entitled Algorithms and Data Structures. Useful techniques are described for the reader to use, applications where they are appropriate are recommended, but detailed analyses of the techniques are not given.

3D digital elevation model generation

This chapter presents techniques used for the generation of 3D digital elevation models (DEMs) from remotely sensed data. Three methods are explored and discussed—optical stereoscopic imagery, Interferometric Synthetic Aperture Radar (InSAR), and LIght Detection and Ranging (LIDAR). For each approach, the state-of-the-art presented in the literature is reviewed. Techniques involved in DEM generation are presented with accuracy evaluation. Results of DEMs reconstructed from remotely sensed data are illustrated. While the processes of DEM generation from satellite stereoscopic imagery represents a good example of passive, multi-view imaging technology, discussed in Chap. 2 of this book, InSAR and LIDAR use different principles to acquire 3D information. With regard to InSAR and LIDAR, detailed discussions are conducted in order to convey the fundamentals of both technologies.

Construction contracts: law and management. 4th edition

This is a fully revised edition of the UK’s leading textbook on the law governing construction contracts and the management and administration of those contracts. Although the legal principles involved are an aspect of general contract law, the practical and commercial complexities of the construction industry have increasingly made this a specialist area. This new edition has been brought up to date with recent cases and developments in the law as it stands at March 2007. The basic approach of the book has been retained. Rather than provide a commentary on standard-form contracts, our approach is to introduce the general principles that underlie contracts in construction, illustrating them by reference to the most important standard forms currently in use. Some of the common standard-form contracts have been revised since the previous edition, and the text has been revised to take account of these changes. Practitioners (consultants, builders, clients and lawyers) will find this an extremely useful source of reference, providing in-depth explanations for all of the features found in contemporary construction contracts, with reasons. A unique feature of this book is the way that it brings together the relevant principles of law with the practical issues arising in construction cases. It is a key text for construction undergraduates and postgraduates as well as for those taking the RIBA Part III and CIOB Part II examinations.

Pocket data mining - big data on small devices

Owing to continuous advances in the computational power of handheld devices like smartphones and tablet computers, it has become possible to perform Big Data operations including modern data mining processes onboard these small devices. A decade of research has proved the feasibility of what has been termed as Mobile Data Mining, with a focus on one mobile device running data mining processes. However, it is not before 2010 until the authors of this book initiated the Pocket Data Mining (PDM) project exploiting the seamless communication among handheld devices performing data analysis tasks that were infeasible until recently. PDM is the process of collaboratively extracting knowledge from distributed data streams in a mobile computing environment. This book provides the reader with an in-depth treatment on this emerging area of research. Details of techniques used and thorough experimental studies are given. More importantly and exclusive to this book, the authors provide detailed practical guide on the deployment of PDM in the mobile environment. An important extension to the basic implementation of PDM dealing with concept drift is also reported. In the era of Big Data, potential applications of paramount importance offered by PDM in a variety of domains including security, business and telemedicine are discussed.

'Response and Responsibility: Theories of the Implied Reader in Children's Literature Criticism'

Reader Response Theory remains popular within Children's Literature Criticism. It seems to offer a sensible resolution to the question of whether meaning derives from text or reader. Through a close reading of one example of this criticism, I suggest that its dualisms are constantly collapsing into appeals to singular authority. at various stages the text or the reader is wholly responsible for meaning. I further suggest that the criticism bypasses the question of interpretation through claiming knowledge of a child reader whose opinions and reactions can be unproblematically accessed. We do not have to worry about reading texts, because we can, apparently, know the child's response to them with certainty. Anything other than this claim to certainty is taken to be a failure of responsibility, a wallowing in the subjective, obscure and perverse. My intention is to reinstate reading as the responsibility of criticism.

The engineer under FDIC's conditions of contract for construction

FIDIC has over the years produced standard forms of contracts for the international procurement of projects. A source of continuing criticism of its Red Book concerns the duality in the traditional role of the engineer as the employer's agent and as an independent third party holding the balance fairly between the employer and the contractor. In response to this and other criticisms FIDIC produced a replacement for it in 1999. The role of the engineer under the new Red Book is critically examined in the light of relevant case law, expert commentaries and feedback from two multidisciplinary workshops with international participation. The examination identified three major changes: (1) a duty to act impartially has been replaced by a duty to make fair determination of certain matters; (2) it is open to parties to allow greater control of the engineer by the employer by stating in the appropriate part of the contract powers the engineer must not exercise without the employer's approval; (3) there is provision for a Dispute Adjudication Board (DAB) to which disputes may be referred. Although the duality has not been eliminated completely, the contract is structured flexibly enough to support those who wish to contract on the basis of the engineer acting solely as the agent of the employer.

Responsiveness to change by standard-form contract drafters: A case study of the FIDIC White Book

Purpose – The purpose of this paper is to focus on the Fédération Internationale des Ingénieurs-Conseils (FIDIC) White Book standard form of building contract. It tracks the changes to this contract over its four editions, and seeks to identify their underlying causes. Design/methodology/approach – The changes made to the White Book are quantified using a specific type of quantitative content analysis. The amended clauses are then examined to understand the nature of the changes made. Findings – The length of the contract increased by 34 per cent between 1990 and 2006. A large proportion of the overall increase can be attributed to the clauses dealing with “conflict of interest/corruption” and “dispute resolution”. In both instances, the FIDIC drafting committees have responded to international developments to discourage corruption, and to encourage the use of alternative dispute resolution. Between 1998 and 2006, the average length of the sentences increased slightly, raising the question of whether long sentences are easily understood by users of contracts. Research limitations/implications – Quantification of text appears to be particularly useful for the analysis of documents which are regularly updated because changes can be clearly identified and the length of sentences can be determined, leading to conclusions about the readability of the text. However, caution is needed because changes of great relevance can be made to contract clauses without actually affecting their length. Practical implications – The paper will be instructive for contract drafters and informative for users of FIDIC's White Book. Originality/value – Quantifying text has been rarely used regarding standard-form contracts in the field of construction.

Boots Book-lovers' Library and the novel: The impact of a circulating library market on twentieth-century fiction

In a Report for the Society of Bookmen in 1928, British publishers estimated that between a quarter to two thirds of all the books they published went to four circulating libraries: Boots, Smith’s, Mudie’s, and The Times bookclub. This essay examines the literary impact of one of the largest of these, Boots Book-lovers’ Library (1899-66), which by 1935 had around 400 libraries attached to their high-street pharmacies catering for the tastes of over one million subscribers a year. Compared to the wealth of studies examining the influence of the library market in the Victorian period, the significance of the subscription libraries as key distributors of fiction in the twentieth century is not well known. But private libraries expanded rapidly in the early twentieth century to cater for what Sidney Dark termed a ‘new reading public’, and records in publishers’ archives indicate that authors routinely adapted their unpublished manuscripts in order to meet the perceived demands of this library reader. This article examines the impact of the Boots Book-lovers’ Library market on authors’ practices of writing and revision, and on literary marketing and censorship. It focuses in particular on the author James Hanley (1897-1985), using unpublished correspondence in the Chatto & Windus archive at the University of Reading to demonstrate how the publisher’s sense of the tastes and expectations of the Boots library reader influenced the editorial process.