This volume thoroughly covers HIV-1 antiretrovirals currently in clinical use, together with their advantages and limitations. HIV-1 inhibitor resistance is discussed in detail, and critical assessments as to what will be required of future antiretrovirals in order to halt viral replication, reduce viral resistance, and alter the state of viral latency are presented. Experts at the forefront of HIV-1 research provide overviews of approaches from the fields of virology, chemical biology and structural biology for obtaining small molecule inhibitors that target viral regulatory and structural components at multiple points in the viral lifecycle. The individual chapters will appeal to scientists and clinicians alike.

This book provides an essential update on the startling array of novel insecticidal toxins and drugs produced by the fascinating bacterium Photorhabdus. The respective chapters describe everything from the detailed molecular biology of the 'Toxin complexes' or Tc's to the complexity of insect immune response in relation to both the bacterium and its nematode vector. The volume covers both primary (toxin production and regulation) and secondary (natural product synthesis and regulation) metabolism and emphasises the potential use of toxins and drugs in both agriculture and medicine. It also discusses in detail two totally novel quorum sensing mechanisms and the likely role of LuxR solos in sensing the presence of different bacterial hosts. Lastly, the book explores the unique case of P. asymbiotica, which seems to have evolved the ability to infect both insects and humans. This synthesis proves that Photorhabdus truly does offer a 'gold mine' for the discovery of novel insecticidal proteins and novel natural products with potential uses in agriculture and medicine alike.

The term "electrophoresis" was first used by Michaelis in 1909, to - scribe the migration of colloids in an electric field. The first practical elect- phoresis method was described by Tiselius in 1937. He used a U-tube filled with buffer layered on top of sample; migration could be monitored using Schlieren optics. In zone electrophoresis, the U-tube was replaced by paper, a support material employed simply to prevent or minimize diffusion of ions, so that ions applied in a narrow strip to the paper will separate and remain as relatively discrete zones. Paper was superceded by a variety of other media, - cluding cellulose acetate, hydrolyzed starch (starch gel), agarose, and polyacry- mide. The latter, in addition to being a support medium, has size-sieving properties. From the basic zone electrophoresis, other means of separation have been dev- oped. These include, isoelectric focusing, isotachophoresis, density gradient el- trophoresis, and various forms of immunoelectrophoresis. In some ways Capillary Electrophoresis (CE) has gone full circle back to the original method of Tiselius. In its simplest form, separations occur in a buffer solution within a glass (fused silica) tube and detection occurs as sample moves past an optical window. CE has rapidly developed into a technique that rivals HPLC in its versatility. All the classical electrophoretic separations-zone, IEF, and isotachophoresis-have their counterparts in CE. Excitingly so, and - thoritatively treated in Clinical Applications of Capillary Electrophoresis.

R. VANFURTH Infection is an inseparable part of communal life, and infections are more common and more severe in hospital communi ties because the sick are more easily infected than the healthy. However, even though progress in the medical sciences has meant that many more patients suftering from relatively severe diseases can be helped at present, the use of more sophisticated and complex treatment leads to impairment of the defence mechanisms in more patients than was the case ten to twenty years ago, and these patients are also more prone to develop an infection. Two questions are particularly relevant in this context. 1) Under what conditions do hospital infections occur? Defects of host defence mechanisms are of great importance in this respect. Such defects can be due to the disease or to the treatment given to the patient. 2) Which of the host defence mechanisms can be affected by a stay in the hospital? Among the factors involved in the host defence against infections (Table I), a number are especially important in this respect. For instance, venepuncture, indwelling catheters, and surgery all cause a breach in the surface structures. Anaesthesia causes temporary impairment of mechanical factors. Vascularization may be defective -- especial ly in the aged and patients with diabetes mellitus -- and this may complicate the healing of wounds in the skin and mucous membranes after surgery."

Mitochondrial cytopathies are mutations in the inherited maternal mitochondrial genome, or the nuclear DNA-mutation. Mitochondrial respiratory chain disorders (RCD) are a group of genetically and clinically heterogeneous diseases, due to the fact that protein components of the respiratory chain are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure and function of mitochondria, including DNA replication, transcription, and translation, all require nuclear encoded genes. Since mitochondria are present in every cell, every tissue, mitochondrial disorder usually affects multiple organs.

This book comprehensively reviews the disease dynamics, distribution, surveillance, epidemiology, diagnosis, control strategies, and management of the desert malaria. It highlights the potential risks of unstable but often exacerbated malaria conflagration as epidemics in the middle of duned desert, a desert oasis, and desert-fringe regions. Further, it reveals the factors inveigled into desert environments due to extensive anthropogenic activities such as canalized irrigation projects, high-yielding new agriculture practices, human concentration, and increased trade. It addresses the impact of irrigation on the malarial dynamics and its coupling to the climate forcing. The book also offers a model for desert transformation into malaria heaven under the changed climatic conditions including high rainfall, humidity, and depletion in temperature. Lastly, it offers insight into malaria epidemiology and disease control in the desert's arid environments. This book is an essential resource for medical entomologists, parasitologists, epidemiologists, and public health researchers.

Hepatic sinusoidal cells such as sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and pit cells play an important role in hemodynamic and metabolic function and are involved in various liver diseases. The frequent involvement of sinusoidal cells in pathologic conditions is explained by the diverse actions of those cells, an understanding of which is essential to clinicians. Generously illustrated, this volume presents results of recent studies on hepatic sinusoidal cells in liver diseases, with an introduction to the structure and function of the various types of sinusoidal cells. The in-depth focus of the book is on the role of hepatic sinusoidal cells in relation to liver injury and regeneration, hepatic sinusoidal microcirculation, alcoholic liver diseases, hepatic fibrosis, liver tumor, liver transplantation, cholestasis, and congenital lipidosis, thus providing a valuable reference source for practitioners and researchers.

New Bacterial Vaccines focuses upon unfulfilled needs for bacterial vaccines. The increase in drug resistance among many bacterial species has increased the need for new bacterial vaccines. This book serves as a comprehensive reference on the major aspects of developing new bacterial vaccines. The distinctive feature of this book is that it focuses upon new vaccines now under development by reviewing key issues for each vaccine target and new technologies being applied to developing new vaccines.
This book should prove useful for students in the life sciences, scientists, developers of vaccines and biotechnology products, clinicians, regulators, and health-care practitioners.

To celebrate the 40th anniversary of the discovery of Natural Killer (NK) cells, this volume focuses on the recent advances in our understanding of NK cell development and differentiation and their acquisition of functional properties, as well as the latest models for NK-cell analysis in mice and applications in clinical medicine. NK cells have travelled a circuitous path from their initial description as 'spontaneous killers' (for some simply an experimental artifact) to being a bona fide subset of innate lymphoid cells with a complementary mode of action in immune defense and an important mediator of immune reactivity in health and disease. Together, these reviews provide a timely and concise picture of the evolution of NK cells as essential agents in immunity and as potent weapons against disease. This book offers an appealing and insightful resource for scientists and clinicians.

James Gray and Ulrich Desselberger have assembled a comprehensive collection of established and cutting-edge methods for studying and illuminating the structure, molecular biology, pathogenesis, epidemiology, and prevention in animal models of infection with rotaviruses, an important cause of infant morbidity and mortality. Presented by experts in the fields of animal and human rotavirus infections and rotavirus vaccine research, these readily reproducible methods detail molecular and other modern techniques, and include relevant background information and various notes to ensure reproducible and robust results. Authoritative and up-to-date, Rotaviruses: Methods and Protocols offers researchers today's benchmark compendium of experimental methods for the investigation of this medically significant virus.

V Pentostam, an uncharacterized complex of Sb and carbohydrate derived from gluconic acid, is concentrated by Leishmania amastigotes via protein binding. Biochemical consequences of the interaction of amastigotes with Pentostam are inhibition of parasite bioenergetics and inhibition of ATP synthesis. REFERENCES 1. J.C. Mottram and G.H. Coombs. Enzyme activities of amastigotes and promastigotes and their inhibition by antimonials and arsenicqls. Exper. Parasitol. 59:151 (1985). 125 2. S.L. Croft, K.D. Neame and C.A. Homewood. Accumulation of [ Sb] sodium stibogluconate by Leishmania mexicana amazonensis and Leishmania donovani in vitro. Compo Biochem. Physiol. 68c:95 (1981). 3. J.D. Berman, J.V. Gallalee, and B.D. Hansen. Leishmania mexicana: uptake of sodium stibogluconate (Pentostam) and pentamidine by parasite and macrophages. Exper. Parasitol. 64:127 (1987). 4. J.D. Berman, D. Waddell and B.D. Hanson. Biochemical meChanisms of the antileishmanial activity of sodium stibogluconate. Antimicrobial Agents Chemotherapy. 27:916 (1985). 5. J.D. Berman, J.V. Gallalee, and J.M. Best. Sodium stibogluconate (Pentostam) inhibition of glucose catabolism via the glycolytic pathway, and fatty acid B-oxidation in Leishmania mexicana amastigotes. Biochem. Pharmacol. 36:197 (1987). 6. D.T. Hart and G.H. Coombs. Leishmania mexicana: Energy metabolism of amastigotes and promastigotes. Exper. Parasitol. 54:397 (1982). 478 EFFECTS OF SINEFUNGIN ON CELLULAR AND BIOCHEMICAL EVENTS IN PROMASTIGOTES OF LEISHMANIA d. donovani Fran~oise Lawrence, and MaIka Robert-Cero Institut de Chimie des Substances Naturelles C.N.R.S.

This volume provides a modern look on the age-old influenza infection and the preventive role of anti-influenza shots. Influenza pandemic outbreaks are unrelenting despite the growing understanding of the molecular basis of viral infection and its spreads. A leap in medical technologies has revolutionized the design of new influenza vaccines. The chapters cover vaccination strategies in various age-groups of people and provide the extensive amount of knowledge on the immune response to influenza vaccination in a spectrum of disease conditions.

In recent years, advanced molecular techniques in diagnostic microbiology have been revolutionizing the practice of clinical microbiology in the hospital setting. Molecular diagnostic testing in general and nucleic acid-based amplification methods in particular have been heralded as diagnostic tools for the new millennium. This third edition covers not only the most recent updates and advances, but details newly invented omic techniques, such as next generation sequencing. It is divided into two distinct volumes, with Volume 1 describing the techniques, and Volume 2 addressing their applications in the field. In addition, both volumes focus more so on the clinical relevance of the test results generated by these techniques than previous editions.

This detailed volume spotlights methods to investigate a variety of virus-host interactions in humans, other mammals, fish, or insects. It explores viruses such as white spot syndrome virus (WSSV), honeybee viruses, Nipah virus, EBV, SVCV, HSV-1, HIV-1, A H1N1, and SARS-CoV-2, as well as applications of techniques such as qPCR, serum antibody responses, 4C analysis, cell membrane fusion, biosensors, computational modelling, quantitative proteomics, and other genetic tools to decipher those viral infections and interactions. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Virus-Host Interactions: Methods and Protocols serves as a valuable resource for researchers both in academia and in the biosciences industry who are engaged in the search for a better understanding of threatening virus-hosts interactions, virus detection, their characterization, and ultimately their taming and control.

Infections caused by fungi have recently attracted the attention of both clinicians and basic researchers given the heavy burden they represent for any health system. The mortality and morbidity rates associated to mycosis are progressively rising simply because some of these diseases are still neglected by health-care workers and due to the changing sensitivity to antifungal drugs displayed by these organisms. In this book, both researchers and clinicians working in the medical mycology field explore the most recent literature about specific mycosis; placing in one concise chapter thoroughly revisions of the current knowledge on virulence factors, recognition by immune cells, immunoevasion, epidemiology, new diagnosis trends and therapeutics. This book is recommended to researchers, physicians and students interested in medical mycology.

Reports of influenza-like illnesses date back to the Middle Ages, and outbreaks of influenza likely afflicted humans long before that. Over the last half century, influenza virus research has led to the development of two classes of antivirals - ion channel and neuraminidase inhibitors. Recently, a method of the artificial generation of an influenza virus was established. This system has been instrumental in the development of novel influenza vaccines and in the understanding of viral pathogenicity and the functions of viral proteins. Influenza Virus: Methods and Protocols summarizes the current techniques that have made this progress possible, ranging from protocols for virus isolation, growth, and subtyping to procedures for the efficient generation of any influenza virus. Written in the successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Influenza Virus: Methods and Protocols seeks to serve both professionals and novices with the techniques used in numerous laboratories around the world that are, thus, the building blocks that underpin almost all influenza virus research.

When we worked on Down Syndrome brain in the past we have been focus ing on adult brain. This was a major step forwards as most work on Down Syndrome was carried out on fibroblasts or other tissues and, moreover, we introduced proteomics to identify and quantify brain protein expression. We considered evaluation of brain protein expression in Down Syndrome brain by and by more important than gene hunting at the nucleic acid level realiz ing the long unpredictable way from RNA to protein. The availability of fetal samples along with the proteomic appproach stimulated and reinforced studies on Down Syndrome brain. And indeed, it was found out that some observations on aberrant protein expression in adult Down Syndrome brain could not be verified in the fetal samples indi cating that neurodegeneration in adult Down Syndrome brain may have been responsible rather than trisomy 21. Using brains from the early second trimester of gestation led to the generation of a series of clues for the under standing of aberrant wiring of the brain in Down Syndrome and enabled the determination of altered key functions in early life; e. g. undetectably low drebrin was observed in Down Syndrome cortex, an integral constituent and marker for dendritic spines, main effectors of cross-talk between neurons. In addition, evaluation of the nature of the neuronal deficits in terms of neuro transmission markers could be established as well as neuronal density in fetal Down Syndrome cortex."

Providing a true integration of pathology with clinical management, this volume presents a practical, comprehensive text on benign and malignant disease of the adult bladder. Integrating pathology, surgical management, oncology and molecular study in a site-specific manner to include the urethra, urinary bladder, ureter and renal pelvis, The Urinary Tract: A Comprehensive Guide to Patient Diagnosis and Management is the first text in adult bladder disease to closely interweave multiple clinical disciplines into each chapter. For the majority of chapters, a pathologist and urologist or urologic oncologist are paired to provide the greatest integration of information for each disease process.

This book explores the broad and diverse biological and physiological impacts of established and newly discovered cyclic di-nucleotide second messenger signaling systems, while also providing descriptions of the intriguing biochemical characteristics of multiple turnover enzymes and receptors. The respective chapters discuss the commonalities and diversity of cyclic di-GMP, cyclic di-AMP and recently discovered cyclic GMP-AMP signaling systems in manifold Gram-negative and Gram-positive bacteria. The global human pathogens Mycobacterium tuberculosis, Vibrio cholerae, Salmonella typhimurium, Escherichia coli and Streptococcus pneumoniae, the facultative human pathogen Pseudomonas aeruginosa, global plant pathogens as exemplified by Xanthomonas campestris and Burkholderia spp., and the omnipresent probiotic Lactobacilli, as well as environmentally important photoautotrophic cyanobacteria, the multicellular Myxococcus xanthus, and chemolithotrophic Acidithiobacillus are among the representatives of the microbial kingdom that are described. In turn, the various aspects of bacterial physiology affected by these signaling systems- e.g. biofilm formation and dispersal, the cell cycle, motility, virulence, production of antimicrobials, fundamental metabolism and osmohomeostasis - are discussed in detail in the context of different microorganisms. Dedicated chapters focus on the population diversity of cyclic dinucleotide signaling systems, their tendency to be horizontally transferred, the cyclic di-GMP signaling system in the social amoeba Dictyostelium, honorary cyclic (di)nucleotides, and the development of strategies for interfering with cyclic dinucleotide signaling in order to manipulate microbial behavior. Taken together, the chapters provide an authoritative source of information for a broad readership: beginners and advanced researchers from various disciplines; individuals seeking a broad overview of cyclic di-nucleotide signaling; and those who want to learn more about specific aspects. Also featuring reviews with a forward-looking perspective, the book offers a valuable source of inspiration for future research directions.

This volume on enzootic bovine leukosis (EBL) and bovine leukemia virus (BLV) is the second in our series "Developments in Veterinary Virology." Each book in this series is devoted to a major virus disease of agricultural significance. The chapters in each volume are planned to supply information on a range of subjects from pathogenesis of the causative virus to vaccination, eradication, and rules regarding disease control. The present volume on enzootic bovine leukosis and bovine leukemia virus updates the reader on the disease and its causative agent and includes the nucleotide sequence of the BLV genome as well as data on its integration into the DNA of the tumor cell. Insights into diagnosis, veterinary legislation, and the economic aspects of EBL are also provided. Intense research conducted on EBL and BLV during the course of a decade is presented in a most concise and in-depth manner, so as to provide the reader with a comprehensive overview of this economically important disease of cattle. I wish to thank the editors, A. Burny and M. Mammerickx, as well as all the authors, for making this excellent book available at a stage when the knowledge on bovine leukemia virus will also contribute to our understanding of the virus causing human AIDS.

Any branch of biology depends for its progress on the development of new concepts and to a lesser, but sometimes crucial, extent on the elimination of erroneous notions. Understanding the roles of bacteria required first the observation that such minute creatures existed, and subsequently the exper imental demonstrations that their presence was necessary for the occurrence of particular phenomena. In this first volume, the authors review the development of scientific understanding of the role of microbes as agents of diverse natural processes. Notably absent is a separate review of the history of microbes as agents of disease, a his tory available in many other publications. Regrettably absent is a review of the his tory of microbes as agents of inorganic transformations, a serious omission that resulted from the illness of the prospective author late in the preparation of this volume. The topic will of course be treated in later volumes, although not predominantly in a historical manner. Otherwise, the emphasis in this volume is on the history of understanding interrelationships between modes of bacterial existence and the inanimate environment. These relationships were established long be fore multicellular, differentiated or ganisms appeared as potential microbial habitats, and their recognition and elucidation contributed greatly to the widened appreciation of bacterial di versity and the importance of these simpler creatures to the physiochemical conditions of the biosphere."

This detailed volume presents timely and authoritative content offering a comprehensive overview of the current state of the art in fungal diagnostics. Moreover, it addresses on-going developments expected to provide a basis for targeted treatment strategies resulting in improved outcome of invasive mycoses. The knowledge of host-related predisposing factors and stratified treatment options facilitating timely onset of adequate antifungal therapy are critical for successful clinical management and outcome of invasive fungal disease (IFD), requiring not only rapid diagnosis of a fungal infection and identification of the causative species, but also assessment of pathogen/host factors related to pathogenicity, susceptibility, and response to treatment. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Human Fungal Pathogen Identification: Methods and Protocols serves as an ideal reference for researchers investigating the ever-growing worldwide healthcare problems involving fungal infections.

This book focuses on the envelope of Gram-positive bacteria including its composition, the latest discoveries in the mechanisms behind its assembly, and its role in pathogenesis. Furthermore, new applications in biotechnology and vaccine development involving these bacteria are discussed in detail. This concise volume consists of eleven chapters by prominent experts in the field, which review the latest findings and current state of knowledge on a range of diverse yet interlinked aspects. This book is written for all researchers, clinicians and technicians engaged in basic or applied science projects on Gram-positive bacteria.