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For most of our existence, humans have manipulated stone into tools that are essential for survival. Generally resistant to degradation, stone tools comprise a large portion of the material culture found at archaeological sites worldwide. Recovery of stone tools during archaeological excavation indicates the location where they were discarded, often tied to where they were used. “Sourcing” refers to attempts to determine the origin of the raw materials used to produce these tools. Knowing the beginning and end points of a tool's use-life, as well as the likely paths it took between those two locations, can offer insight into trade and procurement patterns. The scholars gathered in this volume employ a variety of unique approaches to real-life contexts in multiple geographic regions. These studies illustrate the numerous, robust options available to archaeologists and researchers today, as well as the problems that must be faced and resolved. Part 1 of the book explores technological approaches to sourcing in conjunction with innovative survey strategies. The chapters describe a particular method while often offering suggestions for improving the chemical analysis. Part 2 focuses on region-specific and methodological sourcing applications. In a concluding review, Michael D. Glascock critiques each of the chapters and presents his views, developed across 40 years of work in the field, on sourcing raw materials. Broadly, these contributions demonstrate how knowledge of lithic sources, geologic processes, the nature of variation, and regional availability can provide a more thorough understanding of past peoples.

This open access peer-reviewed volume was inspired by the UNESCO UNITWIN Network for Underwater Archaeology International Workshop held at Flinders University, Adelaide, Australia in November 2016. Content is based on, but not limited to, the work presented at the workshop which was dedicated to 3D recording and interpretation for maritime archaeology. The volume consists of contributions from leading international experts as well as up-and-coming early career researchers from around the globe. The content of the book includes recording and analysis of maritime archaeology through emerging technologies, including both practical and theoretical contributions. Topics include photogrammetric recording, laser scanning, marine geophysical 3D survey techniques, virtual reality, 3D modelling and reconstruction, data integration and Geographic Information Systems. The principal incentive for this publication is the ongoing rapid shift in the methodologies of maritime archaeology within recent years and a marked increase in the use of 3D and digital approaches. This convergence of digital technologies such as underwater photography and photogrammetry, 3D sonar, 3D virtual reality, and 3D printing has highlighted a pressing need for these new methodologies to be considered together, both in terms of defining the state-of-the-art and for consideration of future directions. As a scholarly publication, the audience for the book includes students and researchers, as well as professionals working in various aspects of archaeology, heritage management, education, museums, and public policy. It will be of special interest to those working in the field of coastal cultural resource management and underwater archaeology but will also be of broader interest to anyone interested in archaeology and to those in other disciplines who are now engaging with 3D recording and visualization.

This book primarily covers the general description of foodborne pathogens and their mechanisms of pathogenesis, control and prevention, and detection strategies, with easy-to-comprehend illustrations. The book is an essential resource for food microbiology graduate or undergraduate students, microbiology professionals, and academicians involved in food microbiology, food safety, and food defense-related research or teaching. This new edition covers the significant progress that has been made since 2008 in understanding the pathogenic mechanism of some common foodborne pathogens, and the host-pathogen interaction. Foodborne and food-associated zoonotic pathogens, responsible for high rates of mortality and morbidity, are discussed in detail. Chapters on foodborne viruses, parasites, molds and mycotoxins, and fish and shellfish are expanded. Additionally, chapters on opportunistic and emerging foodborne pathogens including Nipah virus, Ebola virus, Aeromonas hydrophila, Brucella abortus, Clostridium difficile, Cronobacter sakazakii, and Plesiomonas shigelloides have been added. The second edition contains more line drawings, color photographs, and hand-drawn illustrations.

At the end of the last Ice Age, sea level around the world was lower, coastal lands stretched further and the continents were bigger, in some cases landmasses were joined by dry land that has now disappeared beneath the waves. The study of the now submerged landscapes that our ancestors knew represents one of the last barriers for archaeology. Only recently have advances in underwater technology reached the stage where a wealth of procedures is available to explore this lost undersea world. This volume considers the processes behind the rising (and falling) of relative sea-levels and then presents the main techniques available for the study and interpretation of the archaeological remains that have survived inundation. Case studies are used to illustrate particular applications. Finally, a review of projects around the world highlights the varying scale and period of sites concerned. Submerged archaeological sites often include the preservation of fragile materials, such as decorated timbers, that shed rare detail on the communities of prehistory; in other cases the features of the landscape context into which they are set can be extraordinarily well-preserved. This is not a book about shipwrecks but about landscapes now lost beneath the waves. It is written for all archaeologists, whether they work on land or at sea, and for all who are interested in the past; it illustrates the shape of the world as it once was and explains why we need to understand it. It offers an easily accessible introduction to the exciting realm of underwater archaeology.

The author, a world-renowned transplant surgeon, scientist, bioethicist and global health expert, is a Tanzanian born into Swahili culture, with ancestral roots in Arabia, the Caucasus Mountains, and Ethiopia. This memoir chronicles the exploration of his multiple identities, taking the reader on an absorbing journey to Russia, the Ottoman Empire, Zanzibar, South Africa, Idi Amin's Uganda, London, Oxford, the Middle East, the US, Canada, and beyond. We meet slaves, royalty, great heroes, Nobel Prize winners, and mass murderers. It is an impassioned call to resist the polarization that is wrenching apart people of different'races,'cultures and religions. Inspired by Gandhi and Martin Luther King, TheGarment of Destiny is a remarkable journey that explores the many facets of identity, its formation and who controls it. Are we who we are-- or who we are as seen by others?'I believe that there is no clash of civilizations,'Daar says,'because we have one human civilization.'

This book presents a comprehensive overview and analysis of mangrove ecological processes, structure, and function at the local, biogeographic, and global scales and how these properties interact to provide key ecosystem services to society. The analysis is based on an international collaborative effort that focuses on regions and countries holding the largest mangrove resources and encompasses the major biogeographic and socio-economic settings of mangrove distribution. Given the economic and ecological importance of mangrove wetlands at the global scale, the chapters aim to integrate ecological and socio-economic perspectives on mangrove function and management using a system-level hierarchical analysis framework. The book explores the nexus between mangrove ecology and the capacity for ecosystem services, with an emphasis on thresholds, multiple stressors, and local conditions that determine this capacity. The interdisciplinary approach and illustrative study cases included in the book will provide valuable resources in data, information, and knowledge about the current status of one of the most productive coastal ecosystem in the world.

It has been known for a number of years that not only pathogenicity islands but also plasmids and bacteriophages are able to carry genes whose products are involved in pathogenic processes. Accordingly, such elements and their products play an important role in pathogenesis due to the intestinal E. coli as well due to Shigellae. Another interesting aspect which is reflected in different articles is that genomes evolve by acquisition of new pieces of DNA following gene transfer, but also by genome reduction. Different mechanisms include the deletion of sequences or the elimination of functions by the accumulation of point mutations or rearrangements.

The International Life Sciences Institute (ILSI) was creat­ ed to promote cooperative efforts toward solving critical health and safety questions involving foods, drugs, cosmet­ ics, chemicals, and other aspects of the environment. The Officers and Trustees believe that questions regarding health and safety are best resolved when government and industry rely on scientific investigations, analyses, and reviews by independent experts. Further, the scientific aspects of an issue should be examined and discussed on an international basis, separate from the political concerns of individual companies. ILSI is pleased to sponsor this set of monographs on the pathology of laboratory animals. This project will be use­ ful in improving the scientific basis for the application of pathologic techniques to health and safety evaluation of substances in our environment. The world wide distribu­ tion of the authors, editors, and Editorial Board who are creating these monographs strengthens the expectation that international communication and cooperation will al­ so be strengthened.

Main Question: G protein coupled receptors are involved in highly efficient and specific activation of signalling pathways. How do GPCR signalling complexes get assembled to generate such specificity? In order to answer this question, we need to understand how receptors and their signalling partners are synthesized, folded and quality-controlled in order to generate functional proteins. Then, we need to understand how each partner of the signalling complex is selected to join a complex, and what makes this assembly possible. GPCRs are known to be able to function as oligomers, what drives the assembly into oligomers and what will be the effects of such organization on specificity and efficacy of signal transduction. Once the receptor complexes are assembled, they need to reach different locations in the cell; what drives and controls the trafficking of GPCR signalling complexes. Finally, defects in synthesis, maturation or trafficking can alter functionality of GPCRs signalling complexes; how can we manipulate the system to make it function normally again? Pharmacological chaperones may just be part of the answer to this question.

Toxicological and pharmacological effects arise when chemicals interact with biophysiological functions in discrete cell types. There is a continuing need to screen novel compounds for their potential therapeutic effects, and once these have been'discovered'to understand their molecular actions, as the basis of using such compounds safely and for rational drug design. Pharmacology now uses all of the sophisticated molecular research techniques that are available for the development of safer and more efficacious drugs. Histochemistry has been usefully applied to developing new drugs (and assessing chemical safley) and is potentially cost effective. The need to test novel substances for their potential adverse effects has raised many questions. Toxicological pathology has moved away from the cataloging of lesions towards understanding the basis of the events that underly cell injury, especially for those secondary consequences of chemical injury that lead to malignancy and chronic disease. The focal nature of toxicologic lesions de­ mands the use of microtechniques to provide data to help understand these questions. Histochemistry is under-utilized, but offers one of the key ap­ proaches necessary to address the problem of understanding interactions between a cell population and a chemical, the modulation of cellular biochem­ istryor the presence of a lesion in a test animal can be rationalised in terms of species differences that have no relevance to man as opposed to those that are of clinical significance or represent a warning of dire consequences to man.

There should be, and in the best of cases there is, a synergy between basic research and patient care. However, this synergy is hard to develop because the techniques required to be a successful researcher are so different from the skills required to be an outstanding physician. Harold R. Roberts, M.D., of the University of North Carolina at Chapel Hill, is an example of a physician-researcher who has benefited from having his feet in both the world of patient care and the world of the laboratory: he has let clinical problems direct his basic research effort and conversely has adopted research advances in his care of patients. Dr. Roberts's long and continuing career has included many research and clinical advances. He was part of the first group to determine the amino acid sequence of the important thrombin inhibitor hirudin and part of the group that prepared the first cryoprecipitates which were the first alternative to plasma as therapy in hemophilia A. Dr. Roberts has made significant advances in understanding the protein chemistry behind hemophilia B; he was among the first researchers to identify some patients as not being completely deficient but instead as having measurable levels of protein and subsequently demonstrated that this protein was dysfunctional. This important advance led him to a classification scheme for patients into Cross Reacting Material (CRM) positive, negative, and reduced. Dr.

Headspace gas analysis is an analytical technique that has been successfully applied to food flavors for over 20 years but has experienced a resurgence of interest and innovation in recent years. In its truest form, headspace analysis represents the direct collection and analysis of the mixture of vapors in the space immediately above a food or beverage. The technique offers several advantages for workers interested in how a product smells and ultimately tastes. It offers the advantages of speed, simplicity, and, more importantly, represents the aroma profile a consumer is likely to experience just before consuming the product. Since only volatile components are collected, the sample is totally free of nonvolatile residues which commonly plague comparison liquid-liquid extracts of the same product. This is the first book devoted to headspace analysis in foods and beverages in more than 20 years. The publication contains chapters on the basic theory of headspace analysis, as well as the theory and application of newly developed headspace techniques, such as solid phase micro extraction, SPME and electronic noses. New concentrating and desorption techniques are described in addition to a raft of food applications including tomato and citrus juices, alcoholic beverages, baguettes, dairy products, lipids, grill flavoring, baked potato, and meat. Chapters on off-flavors as well as aroma-food matrix interactions are also included.'This is the bible of headspace analysis. If you are involved in, or planning on becoming involved, or want to learn more about, this incredible subject, then buy this book immediately!'– Aubrey Parsons, governing council member, International Union for Food Science and Technology

The International Life Sciences Institute (ILSI) was estab­ lished to stimulate and support scientific research and edu­ cational programs in nutrition, toxicology, and food safe­ ty; and to encourage cooperation in these programs among scientists from universities, industry, and government in order to facilitate the resolution of health and safety issues. The officers and trustees of ILSI believe that questions re­ garding health and safety are best resolved when govern­ ment and industry rely on scientific investigations, analy­ ses, and reviews by independent experts. This process is furthered by the examination and discussion of issues on an international basis. ILSI is pleased to sponsor this set of monographs on the pathology of laboratory animals. This project collectively brings together the most comprehensive information on non-neoplastic and neoplastic lesions that occur in com­ monly used laboratory animals. The international compo­ sition of the authors, editors, and editorial board who have contributed to these monographs strengthens our expecta­ tions that understanding and cooperation will be strength­ ened worldwide through this series.

In 1996 the International Committee for Taxonomy of Viruses (ICTV) recognized the name Nidovirales, as the formal name for Coronaviridae and A rteriviridae. In recognition of this change, and in response to the wishes of our colleagues we named this meeting for the first time'The International Symposium of Nidoviruses'. The meeting in the wooded environment of Lake Harmony, Pennsylvania, provided a stimulating opportunity for assessing the progress made in the field since the last meeting in Segovia Spain in 1997. Over 150 scientists from academia and industry attended the meeting. The meeting hosted senior members of the Nidovirus community, some of whom have been studying the subject for over 20 years, as well as younger scientists, the next generation of Nidoviro10gists. The traditional informal format, the shared meals, the social activities and the relatively inexpensive venue made the meeting a popular adventure. In her opening remarks Susan Weiss showed pictures from previous meetings, reminding us how young we used to look. Neal Nathanson was our keynote speaker at the opening night, giving an overview on how viral pathogenesis studies helped in shaping the evolution of viral research and vaccine development. The scientific program of the meeting was divided into 9 sessions including lO keynote presentations. The meeting opened with a session on epidemiology, evolution and genome structure. Sasha Gorbalenya shared with us insights gained from comparative sequence analysis, emphasizing the unifying traits among nidovriuses, but also pointed out the remaining'black holes'.

Advances in biochemistry, cell biology, genome-wide mutagenesis - coupled with molecular technology, including gene microarray and transgenic and knock-out animals - have been instrumental in understanding the cellular processes and molecular pathways of self-tolerance and autoimmune diseases. The molecular definition of these pathways and processes has led to novel treatments for certain auto-immune diseases that are based on the pathogenesis of diseases rather than on broad-spectrum immunosuppression. This book reviews many of these current developments and proposes future novel approaches for understanding the pathogenesis of auto-immune diseases and designing novel therapy. This book covers three major areas of auto-immunity: the basic mechanisms of immunological tolerance, pathogenesis of auto-immune diseases, and some novel therapies. This book should be useful for immunologists, molecular biologists, rheumatologists, and clinical scientists.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases – and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume II extends into the role of phosphoinositides in membrane organization and vesicular traffic. Endocytosis and exocytosis are modulated by phosphoinositides, which determine the fate and activity of integral membrane proteins. Phosphatidylinositol(4,5)-bisphosphate is a prominent flag in the plasma membrane, while phosphatidylinositol-3-phosphate decorates early endosomes. The Golgi apparatus is rich in phosphatidylinositol-4-phosphate, stressed cells increase phosphatidylinositol(3,5)-bisphosphate, and the nucleus has a phosphoinositide metabolism of its own. Phosphoinositide-dependent signaling cascades and the spatial organization of distinct phosphoinositide species are required in organelle function, fission and fusion, membrane channel regulation, cytoskeletal rearrangements, adhesion processes, and thus orchestrate complex cellular responses including growth, proliferation, differentiation, cell motility, and cell polarization.

A very early step in microbial colonization and pathogenesis is that involving recog­ nition of the host by the microbe. In the final analysis such recognition is due to interaction between specific molecules on the two sides, without which host and microbe would ignore each other. It is therefore exciting to learn the rules that govern host-microbe interaction at to a large extent determines whether or not we are infected by the molecular level, which influenza virus, leishmanias, staphylococci and other pathogens. This book is a compendium of the addresses delivered at a symposium on molecular interaction at Porvoo, Finland in August 1991. Realizing that there are no a priori differ­ ences in receptor recognition in viruses, eukaryotic parasites and bacteria, we freely inter­ mingled these microbes at the symposium, and in this book. We found the interdisciplinary discussions and comparisons both educative and stimulating. Thus the book is divided into parts that focus on host cell receptors, on microbial recognition molecules and molecules that mediate microbial interaction with a host cell receptor and, briefly, on the molecular events that follow. Although many microbes and many cellular receptors are missing from the book -owing to the limited duration and size of the symposium -the articles presented here constitute an impressive body of examples of how initial host-microbe interaction can come about. We believe that as such the book is a useful and interesting overview of the mechanisms and principles involved in these interactions.

The meeting on experimental hepatocarcinogenesis which took place in Spa, Belgium at the end of May 1987 was the Second European Meeting. About 100 scientists, mostly from Europe but also from the United States, met there for three days in a very friendly atmosphere to exchange knowledge and ideas on experimental and human liver carcinogenesis. The main topics discussed during the meeting included general reviews on hepatocarcinogenesis, experimental models of hepa­ tocarcinogenesis, biology of hepatocarcinogenesis, and in vitro studies in hepatocarcinogenesis. They are all covered by the various chapters of this proceedings volume, which reflects the present state of knowledge in this important field of cancer research. The final aim of that research is to understand the basic mechanisms of carcinogenesis. The liver offers a parti­ cularly interesting tool to reach such a goal. Indeed, its biochemistry, its morphology, and its physiology are very diverse, but relatively well known. Various protocols have been developed to produce hepatocellular carcinomas or other malignant tumors. Their appearance is most often preceded by phenotypically altered foci and nodules which have been isolated and characterized. The major cell populations of normal, neoplastic, and malignant livers have been cultivated.

High-fidelity chromosomal DNA replication underpins all life on the planet. In humans, there are clear links between chromosome replication defects and genome instability, genetic disease and cancer, making a detailed understanding of the molecular mechanisms of genome duplication vital for future advances in diagnosis and treatment. Building on recent exciting advances in protein structure determination, the book will take the reader on a guided journey through the intricate molecular machinery of eukaryotic chromosome replication and provide an invaluable source of information, ideas and inspiration for all those with an interest in chromosome replication, whether from a basic science, translational biology and medical research perspective.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases – and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume I untangles the web of these enzymes and their products, and relates them to function in health and disease. Phosphoinositide 3-kinases and 3-phosphatases have received a special focus in volume I, and recent therapeutic developments in human disease are presented along with a historical perspective illustrating the impressive progress in the field.

Transcription factors are the molecules that the cell uses to interpret the genome: they possess sequence-specific DNA-binding activity, and either directly or indirectly influence the transcription of genes. In aggregate, transcription factors control gene expression and genome organization, and play a pivotal role in many aspects of physiology and evolution. This book provides a reference for major aspects of transcription factor function, encompassing a general catalogue of known transcription factor classes, origins and evolution of specific transcription factor types, methods for studying transcription factor binding sites in vitro, in vivo, and in silico, and mechanisms of interaction with chromatin and RNA polymerase.

Comprehensive examination of the current understanding of pathogen adaptation and microevolution.

Endotoxins are potentially toxic compounds produced by Gram-negative bacteria including some pathogens. Unlike exotoxins, which are secreted in soluble form by live bacteria, endotoxins are comprised of structural components of bacteria. Endotoxins can cause a whole-body inflammatory state, sepsis, leading to low blood pressure, multiple organ dysfunction syndrome and death. This book brings together contributions from researchers in the forefront of these subjects. It is divided into two sections. The first deals with how endotoxins are synthesized and end up on the bacterial surface. The second discussed how endotoxins activate TLR4 and, in turn, how TLR4 generates the molecular signals leading to infectious and inflammatory diseases. The way endotoxins interact with the host cells is fundamental to understanding the mechanism of sepsis, and recent research on these aspects of endotoxins has served to illuminate previously undescribed functions of the innate immune system. This volume presents a description of endotoxins according to their genetic constitution, structure, function and mode of interaction with host cells.

Since the establishment of the DNA structure researchers have been highly interested in the molecular basis of the inheritance of genes and of genetic disorders. Scientific investigations of the last two decades have shown that, in addition to oncogenic viruses and signalling pathways alterations, genomic instability is important in the development of cancer. This view is supported by the findings that aneuploidy, which results from chromosome instability, is one of the hallmarks of cancer cells. Chromosomal instability also underpins our fundamental principles of understanding tumourigenesis: It thought that cancer arises from the sequential acquisition of genetic alterations in specific genes. In this hypothesis, these rare genetic events represent rate-limiting ‘bottlenecks'in the clonal evolution of a cancer, and pre-cancerous cells can evolve into neoplastic cells through the acquisition of somatic mutations. This book is written by international leading scientists in the field of genome stability. Chapters are devoted to genome stability and anti-cancer drug targets, histone modifications, chromatin factors, DNA repair, apoptosis and many other key areas of research. The chapters give insights into the newest development of the genome stability and human diseases and bring the current understanding of the mechanisms leading to chromosome instability and their potential for clinical impact to the reader.

Knowledge of cholesterol and its interaction with protein molecules is of fundamental importance in both animal and human biology. This book contains 22 chapters, dealing in depth with structural and functional aspects of the currently known and extremely diverse unrelated families of cholesterol-binding and cholesterol transport proteins. By drawing together this range of topics the Editor has attempted to correlate this broad field of study for the first time. Technical aspects are given considerable emphasis, particularly in relation cholesterol reporter molecules and to the isolation and study of membrane cholesterol- and sphingomyelin-rich'raft'domains. Cell biological, biochemical and clinical topics are included in this book, which serve to emphasize the acknowledged and important benefits to be gained from the study of cholesterol and cholesterol-binding proteins within the biomedical sciences and the involvement of cholesterol in several clinical disorders. It is hoped that by presenting this topic in this integrated manner that an appreciation of the fact that there is much more that needs to be taken into account, studied and understood than the widely discussed'bad and good cholesterol'associated, respectively, with the low- and high-density lipoproteins, LDL and HDL.

Lipids are functionally versatile molecules. They have evolved from relatively simple hydrocarbons that serve as depot storages of metabolites and barriers to the permeation of solutes into complex compounds that perform a variety of signalling functions in higher organisms. This volume is devoted to the polar lipids and their constituents. We have omitted the neutral lipids like fats and oils because their function is generally to act as deposits of metabolizable substrates. The sterols are also outside the scope of the present volume and the reader is referred to volume 28 of this series which is the subject of cholesterol. The polar lipids are comprised of fatty acids attached to either glycerol or sphingosine. The fatty acids themselves constitute an important reservoir of substrates for conversion into families of signalling and modulating molecules including the eicosanoids amongst which are the prostaglandins, thromboxanes and leucotrienes. The way fatty acid metabolism is regulated in the liver and how fatty acids are desaturated are subjects considered in the first part of this volume. This section also deals with the modulation of protein function and inflammation by unsaturated fatty acids and their derivatives. New insights into the role of fatty acid synthesis and eicosenoid function in tumour progression and metastasis are presented.

Although creatine was discovered already in the 1830s, it is only in recent years that its crucial role for human health and general well-being has been increasingly realized and appreciated. A number of beneficial health effects have been ascribed to oral creatine supplementation, such as neuroprotective, ergogenic, anti-diabetic, anti-inflammatory, antiviral, or antitumor effects. Creatine may even improve memory and intelligence. In the present book, emphasis is placed on the intricate interplay between creatine and creatine kinase function on one hand, and proper brain function, neurodegenerative disease and/or neuroprotection on the other hand. The book also elaborates on the recently identified inborn errors of creatine biosynthesis and transport, the so-called cerebral creatine deficiency syndromes. The clinical hallmarks of these disorders are mental retardation, epilepsy, autistic-like behaviour, and speech and language delay. In addition, the muscle growth- and strength-promoting effects, the pharmacokinetics and the safety of oral creatine supplementation are discussed. Finally, the present book outlines the emerging'systems biology'approaches for understanding the pleiotropic effects of creatine and creatine kinase, and hypothesizes on the most promising and influential future avenues of research towards creatine-based nutritional strategies for the prevention of neurological disease, and for improving the quality of life in general.

Ever since my days in veterinary school, I was fascinated with the field of microbiology. I always wondered how such a small microscopic organisms are capable of causing infections in other living organisms; big or small, young or old, and healthy or immunocompromised. The subject captured my imagi- tion. Many of the same microorganisms that cause diseases in animals also infect humans. In recent days, pathogens of animal origin impose even greater concern with increasing threat of avian influenza to cause pandemic, and spread of deadly bovine spongiform encephalopathy (mad cow disease) and many bacterial pathogens such as Listeria, E. coli O157:H7, Salmonella, Yersinia, and Campylobacter. I am especially intrigued by the cunning strategy pat- gens employ for their survival in a host and their exploitation of host cellular machinery to promote their own invasion into the host. Pathogenic mechanism is complex and unraveling that process requires great minds. Today, mic- biologists, cell biologists, and immunologists employing many sophisticated molecular tools are unraveling that secret at a very fast pace. Thus it requires a great deal of efforts to compile and update information in a textbook and it was rather a monumental task. My goal with this book was to paint a bigger picture of pathogenic mechanism of foodborne pathogens, which are responsible for many of modern day outbreaks, and diseases worldwide, and narrate the subject with easy to comprehend illustrations.

A volume within the Subcellular Biochemistry series is an appropriate setting for the first multi-author book devoted to the new family of antioxidant and cell signalling proteins, the peroxiredoxins. Within the antioxidant and cell signalling fields, even the existence of the peroxiredoxins has yet to be appreciated by many; with this book we aim to rectify this situation. We have tried to select diverse chapter topics to cover relevant aspects of the subject and to persuade knowledgeable authors to contribute a manuscript. As almost inevitable, a few authors let us down by failing to respond, others could not submit a manuscript in time for personal reasons. These unfortunately were two of the pioneers, Earl Stadtman and Sue Goo Rhee, but we appreciate that they communicated a lot of details that helped us to reconstruct the early phase of peroxiredoxin enzymology. We have thus compiled a book that competently covers the peroxiredoxin field from its beginnings through to currently relevant topics. In the introductory Chapter 1 we provide a short historical survey of the subject, based upon the early structural and enzymic studies on peroxiredoxins, and then lead into some of our current personal interests, such as the likely continuing contribution of transmission electron microscopy (TEM) for the study of high molecular mass peroxiredoxin complexes and the association of peroxiredoxins with other proteins, and the targeting of drugs against microbial peroxiredoxins, as future therapeutic approaches.

This volume summarizes the new developments that made subcellular proteomics a rapidly expanding area. It examines the different levels of subcellular organization and their specific methodologies. In addition, the book includes coverage of systems biology that deals with the integration of the data derived from these different levels to produce a synthetic description of the cell as a system.

This topic is a new entry in the area of cellular calcium signaling: yet, it now spans the entire area, with discoveries that cover both genetic and acquired pathologies, even offering glimpses in the direction of therapy. Cellular calcium homeostasis, and thus calcium signalling, is mainly regulated by membrane intrinsic proteins and calcium sensor proteins. Both classes may be involved in pathological processes that affect both human and animals, ranging from common and important diseases (e.g. migraine, diabetes, epilepsia, manic depression, infertility, various types of cancer, Alzheimer's disease, muscular dystrophy) to rare genetic conditions (e.g., a number of genetic heart conditions, autoimmune retinopathies, night blindness, hereditary amyloid polyneuropathy, malignant hyperthermia, cerebellar ataxia, atherothrombotic disease). Clearly, the topic has now become not only very large, but also very stimulating. Its extensive critical coverage is likely to eventually stimulate fruitful interdisciplinary discussions.

In this book, a worldwide panel of leading experts discuss the role of inflammation in the pathogenesis of major chronic diseases and the current controversy regarding risk versus benefit of selective cyclooxygenase-2 (COX-2) inhibitors. The authors provide exciting and enlightening perspectives on COX-2 and related molecular targets in the future of medicine, including historical perspectives.

It is more evident now than ever before that dynamic organization of human genome into nucleoprotein structure, chromatin confers the unique regulatory mechanisms for most of the cellular phenomena, which include replication, transcription, DNA repair, recombination and also apoptosis. The dynamic nature of the chromatin is regulated by chromatin modifications (epigenetic alterations), remodeling, histone chaperones and functional interactions of different chromatin interacting n- histone proteins. Dysfunction of this highly inter connected machineries disturb the cellular homoeostasis, and thereby causes several diseases. As we advance in our knowledge of chromatin function and also disease mechanisms in more details, their causal relationship is becoming more evident. This has lead to the identification of chromatin function as target for new generation therapeutics. In the light of these advances, it happens to be the right time to explore current insights into various aspect of chromatin and disease connection under one cover. Authors who are actively involved in chromatin research and have made several original contributions to develop latest paradigms in the field have written the chapters of this book. Significantly, the authors'repertoire is truly international. They come from eight different countries of Asia, Europe and America. The book has been divided into three different parts. Part I introduces the reader to the dynamic nature of chromatin structure and its link to diseases. First two chapters in this part deal with the chromatin architecture, chromatin dynamics in the cell cycle and molecular mechanism of chromatin remodeling.

This volume describes the current status of the biology of inositols and phosphoinositides with an emphasis on the development in the area since the publication of volume 26 in 1996 in this series. The progress made in dissecting the genetics, structure and evolution of the seminal enzyme for synthesis of inositol in the biological system has driven the understanding of the enzyme forward. With the current genomic and proteomic tools in place the new role of inositols, inositol phosphates and phosphoinositides in cell signaling or stress response has been explored. These advances are described.

Although most strains of E. coli bacteria are harmless and live in the intestines of healthy humans and animals, several strains can produce powerful toxins and cause severe illness in humans. This versatile pathogen is best known for being transmitted to humans through contaminated foods — such as undercooked meat and unpasteurized fruit juice — and has attracts much attention when serious outbreaks occur. E. coli is capable of causing a wide variety of diseases — from urinary tract infections to meningitis. A considerable amount of media coverage has recently been devoted to one particular strain of E. coli, responsible for an estimated 73,000 cases of infection and 61 deaths in the United States each year. Knowing more about the biology, the evolution, and the genetic basis of this pathogen is crucial to future prevention of infection and illness. Pathogenic E. coli is a unique, comprehensive analysis of the biology and molecular mechanisms that enable this ubiquitous organism to thrive. Leading investigators in the field discuss the molecular basis of E. coli pathogenesis followed by chapters on genomics and evolution. Detailed descriptions of distinct strains reveal the molecular pathogenesis of each and the causes of intestinal and extra-intestinal infections in humans. Pathogenic E. coli concludes with a presentation of virulance factors, common to two or more pathotypes. This unique collection presents timely and vital information on understanding the inner workings of E. coli, which will lend key insights into disease prevention research. - Single source of information of E. coli pathogenesis - Expert authors - Comprehensive coverage - Molecular mechanisms - Biology, evolution and genomics - Recent advances

Pathogenic bacteria have unique biological properties, which enable them to invade a host and cause sickness. The molecular bases of these biological properties are the determinants of pathogenicity, and the research objectives are to recognize them, identify them chemically and relate their structure to function. Most of our present knowledge comes from studies with cultures in vitro. However, there is a rising interest in bacterial behaviour in the infected host and new methods have been developed for studying it. This book describes those methods and shows how they, and a recent surge in conventional studies, are shedding light on the activities of bacterial pathogens in vivo. It discusses bacterial and host factors that operate in vivo to cause illness, showing how phenomena recognized in vitro relate to behaviour in vivo and, if evidence of relevance is not available now, indicating how it might be obtained.

Designed as an upper-level textbook and a reference for researchers, this important book concentrates on central concepts of the bacterial lifestyle. Taking a refreshingly new approach, it present an integrated view of the prokaryotic cell as an organism and as a member of an interacting population. Beginning with a description of cellular structures, the text proceeds through metabolic pathways and metabolic reactions to the genes and regulatory mechanisms. At a higher level of complexity, a discussion of cell differentiation processes is followed by a description of the diversity of prokaryotes and their role in the biosphere. A closing section deals with man and microbes (ie, applied microbiology). The first text to adopt an integrated view of the prokaryotic cell as an organism and as a member of a population. Vividly illustrates the diversity of the prokaryotic world - nearly all the metabolic diversity in living organisms is found in microbes. New developments in applied microbiology highlighted. Extensive linking between related topics allows easy navigation through the book. Essential definitions and conclusions highlighted. Supplementary information in boxes.