Molecular Biology Intelligence Unit – serie

This volume provides broad insights to the most recent discoveries in telomere biology, with current applications in tumour diagnostics and future potentials in therapy. Special features of diverse organisms are presented, with ciliates, the "telomerase discoverer organisms"; yeasts, the "molecular genetisists' toy for eukaryotes"; including plants and insects as well. Twenty-eight chapters were written by a group of research scientists, working in the telomere/telomerase fields today.

This volume aims to extract and summarize all information about CAK by pointing out commonly accepted facts and unresolved issues. It takes the reader from yeast to mammals and describes all areas that CAK is thought to be involved in. This volume is designed to serve newcomers to the field as well as specialists; any person interested in cell growth, signal transduction and cancer will find this a useful tool to own.

This volume provides an exhaustive review of the most current knowledge of the composition, architecture and dynamics of the nuclear envelope. In contrast to other comprehensive works on cellular membranes in general, this book is the first to specifically address the nuclear envelope. Experts in the field relate the different domains of the nuclear envelope, their biogenesis, their composition, their mode of targeting to chromosomes and how they dissociate from chromosomes upon cell division. A wealth of information from several experimental systems is provided, such as dividing somatic cells, embryos and nuclear assembly assays in cell-free extracts, in a wide range of vertebrate and invertebrate organisms ranging from humans to yeast. The book also contains up-to-date reviews on the relationship between mutations in proteins of the nuclear envelope and Emery-Dreifuss muscular dystrophy. The breadth of topics covered in what may seem to be a field as narrow as the nuclear envelope makes this volume a valuable reference.

The volume offers insight into the key research topics that involve caspases. Leading experts from various areas of biology and medicine have compiled this volume so that both the novice and the professional will use this as the main reference for caspases for years to come. The reader will learn about the role of caspases in apoptosis signaling, inflammation and cancer therapy while being updated on the methodology used to study caspases and the efforts of pharmaceutical research in targeting caspases.

The volume assembles current information on the role of ceramide as a signalling molecule in 16 chapters written by leading workers in this area. Specific attention is given to mechanisms of analysis of ceramide and its biophysical properties, on enzymes of ceramide metabolism and down-stream targets of ceramide, on the cross-talk of ceramide signalling with other signalling pathways, and on the role of ceramide in neuronal signalling. Finally, the book closes with a section on the therapeutic implications of ceramide action, in the areas of cannabinoid action, chemotherapy, and atherosclerosis, and illustrates the potential medical significance of delineating the roles of ceramide in cell signalling. This is the first volume specifically devoted to ceramide signalling, and will act as an invaluable resource for basic and medical researchers and graduate students wishing to get a state of the art overview of this rapidly moving field.

In this contribution, several specialists describe the current knowledge on the molecular networks that regulate cell cycle progression, with an emphasis on the G1 phase of the cell cycle. The first part of Regulation of G1 Phase Progression is concerned with the individual molecules that form the network, including cyclins, cyclin-dependent kinases, inhibitors of these kinases and retinoblastoma and p53. The second section describes the signaling cascades by which external factors influence the cell cycle network, including mitogens, the extracellular matrix, nutrients and oxygen radicals. The last section describes the effects of specific external conditions on cell cycle progression and are presented such as serum starvation and subsequent re-addition and stress conditions (heat, osmolarity). The final two chapters describe the relation between cell cycle progression with cell differentiation and with apoptosis.

This book provides information on the molecular interactions between host cell organelles and pathogens, which have developed strategies to survive within infected cells. Chapters are grouped into five sections: I. Endocytosis and phagocytosis. Collectively, the chapters of this section review basic knowledge regarding intracellular organelles are involved in membrane interactions with pathogen-containing vacuoles. II. Professional and non-professional phagocytes. Here the authors describe the major differences between the two host cell types, which can be infected by microorganisms. III. Maturation pathways of bacteria-containing vacuoles. Molecular interactions between vacuoles and intracellular organelles leading to the search of the Holy Grail, the replication niche, are described. IV. Host response. Host cells are able to react against intruders and eventually mount host responses. In these chapters the various types of host response mechanisms against intracellular intruders are reviewed. V. Co-evolution. In these final chapters, the question is addressed of whether knowledge of bacteria-host cell interactions will be acquired fast enough to find the necessary tools for controlling microorganism development.

The Annexins is focused on a specific family of calcium and membrane-binding proteins, annexins, ubiquitously spread within living organisms, including animals, plants and fungi. The volume covers important areas of annexinology. The characterization of structural-functional relationship within the annexin family of proteins, together with emerging transgenic animal models, provides an up-to-date overview of potential physiological roles of annexins. Growing evidence of participation of annexins in human diseases, called annexinopathies, related to disturbances in signal transduction, vesicular traffic, ion homeostasis and energy metabolism within the cell. The book will attract a broad scientific audience, not only scientists interested in annexins, but also others involved in multidisciplinary studies, as well as undergraduate and postgraduate students. It can be used in courses relating to special topics such as calcium homeostasis, calcium-binding proteins, membrane structure and transport properties, various signal transduction pathways, and membrane trafficking.

In vertebrates, the integrin family includes 24 members. As the alpha-chains were sequenced, some were observed to have an inserted domain similar to the A domain in several matrix and complement proteins. This inserted ligand binding domain is interactive and was called the I domain in integrins. More recently structural data have shown that an integrin beta-chain also contains an I domain. Nine of the currently known 18 alpha-chains contain an I domain. This book systematically goes through the current knowledge about these integrins, including the newest additions to the integrin family, the collagen-binding alpha10beta1 and alpha11beta1 integrins. The book discusses ligand binding, signalling properties, knock-out phenotypes and possible involvement in disease. This book comprehensively reviews the current knowledge about I domains in integrins and will serve as a useful reference book for scientists in this field.

The CFTR chloride channel is one of the most well studied transport proteins in biology. Yet there remain many mysteries about the functional properties and biological roles of this ABC transporter. The Cystic Fibrosis Transmembrane Conductance Regulator addresses a select series of `hot' topics that relate to the function of CFTR, and the links between CFTR dysfunction and human disease (i.e., cystic fibrosis). The timeliness of these topics distinguishes this collection from previous volumes of this type. Given the general interest in CFTR, this collection will appeal to a broad readership with interests in CFTR, cystic fibrosis, ion channels and ABC transporters.

Wnt genes code for a family of secreted glycoproteins which fulfil important functions during the development of vertebrates and invertebrates. Wnts regulate as different aspects as differentiation, proliferation, cell migration, and cell polarity. Wnt proteins are able to activate different intracellular signaling cascades. This book describes different aspects of Wnt signaling during development of different species like the mouse, Xenopus, chicken, C. elegans or Drosophila and in different cellular contexts like heart formation or limb bud patterning. By doing such, this book provides, for the first time in printed form, an overview of the function of Wnt proteins during development. This book will be of interest to all professionals in the field of Wnt signaling, signal transduction or animal development.

Translation Mechanisms provides investigators and graduate students with overviews of recent developments in the field of protein biosynthesis that are fuelled by the explosive and synergic growth of structural biology, genomics, and bioinformatics. The outstanding progress in our understanding of the structure, dynamics, and evolution of the prokaryotic and eukaryotic translation machinery, as well as applications in medicine and biotechnology, are described in 26 chapters covering recent discoveries on: -the subtleties of tRNA aminoacylation with natural and unnatural amino acids. -the control of mRNA stability, a key step of gene regulation. -ribosome structure and function, in the era of the atomic-crystal resolution of the ribosome. -the regulation of the biosynthesis of the translational machinery components. -the action of a variety of inhibitors of translation and the prospect for clinical studies.

oltage-gated calcium channels are essential mediators of a range of physiological functions, including the communication between nerve Vcells, the regulation of heart beat, muscle contraction, and secretion of hormones such as insulin. Consequently, these channels are critical phar­ macological targets in the treatment of a variety of disorders, such as epi­ lepsy, hypertension, and pain. Voltage-gated calcium channels have there­ fore been subject to intense study by numerous investigators over the past few decades, and an immense body of work has accumulated. In this book, we provide the first comprehensive overview of our current state of knowl­ edge concerning this exciting field of research. Leading off with a general review of calcium signaling and techniques to measure calcium channel ac­ tivity, the book delves into a provocative overview of the history of the cal­ cium channel field, contributed by one of the key pioneers in the field. Dr. Richard Tsien. This is followed by an in depth review of the biochemical and molecular biological characterization of calcium channel genes by Drs. Catterall and Snutch whose research has resulted in major advances in the calcium channel field. A number of chapters are dedicated towards various aspects of calcium channel structure and function, including channel gat­ ing, permeation, modulation and interactions with members of the exo- totic machinery—contributed by both established leaders and rising stars in the field.

This book is the first comprehensive volume on the "Nramp family", highlighting the physiological importance of Nramp proteins as metal transporters. The molecular knowledge of these membrane proteins is presented from an evolutionary perspective, considering Nramp cellular function and mechanism of transport in key model organisms. The pathological significance of Nramp genetic polymorphism is discussed with emphasis on metal homeostasis and microbial infection. The chapters were contributed by leading investigators, providing a timely state of the art book in this rapidly growing field. The Nramp Family will be useful to a broad community of scientists interested in metal transport and molecular biology. It will be of interest to the research audience in the broad fields of metal ions and molecular medicine.

The B7-CD28 family molecules are probably the most intensively studied receptor-ligand systems in the field of immunology. This is evident from the explosive accumulation of literature, particularly in the last ten years. Recent years have witnessed rapid discoveries and characterization of new receptors and ligands in the family. These new pathways, although still in their infancy, have already brought much excitement to the field. However, until now, there has been no single volume to cover this entire area. This book was created to bring together state-of-the-art information and critical thinking from the leading investigators. This book covers significant territory of this rapidly moving field from structural biology and biochemical signalling to immunological functions and their potential applications in the treatment of human diseases. This handbook and reference guide is for immunologists, health professionals, medical students and graduate students in life science field.

This book is unique in providing pertinent information on the various established roles carbohydrate play in the immune system and how the innate and adaptive immune systems respond to this type of microbial antigens. The editors selected only topics that have established basic and clinical relevance to this field. The topics from basic research are organised like a textbook, in order to guide the readers through complex sets of events that lead to clearance of or to immune responses toward carbohydrate antigens. The book is clear, concise and contains fully annotated summaries of the key basic and practical information on carbohydrate immunology from current literature. These topics are written by investigators from various disciplines (chemistry, medicine, biochemistry, glycobiology and immunology), creating a fine balance in the point of views presented in the book. It explores the challenges and rewards of understanding the importance of carbohydrates and glycoconjugates in health and disease, applying new knowledge from carbohydrate immunology in improving or developing novel sugar-based therapeutics, and vaccines and medicines. This book is most suitable for glycobiologists and immunologists, but many researchers whose interests, background and expertise are in any of the fifteen topics presented in this book will also find it appealing. It is also a valuable resource for postgraduate students, clinicians or anyone else who is curious about the role of carbohydrates in immunology, and would like to see the topics combined under one cover and in relation to each other.

The book focuses on the latest discoveries on calreticulin, calnexin and other endoplasmic reticulum proteins. Calreticulin has been implicated to affect diverse cellular function and play a role in many pathologies including protein folding disorders, cardiac pathologies, cancer and autoimmunity. This book contains contributions from the world leaders in the area of endoplasmic reticulum function, protein folding, Calcium homeostasis and autoimmunity. It raises many intriguing questions about calreticulin, calnexin and the endoplasmic reticulum and gives a unique opportunity to realize the significance of these calcium-binding chaperones. The book is unique in every respect and we are not aware of any other publication focusing on these aspects of endoplasmic reticulum biology. Because of a central role of endoplasmic reticulum, calreticulin and calnexin in virtually all cellular functions, the book should be of interest to everyone in the biological sciences.

Insulin-like growth factors are ubiquitously expressed and are crucial for growth and function of almost all cells. Together with their binding proteins and receptors, they form a widely studied biological system involving many proteins and characterized by complex interactions. In addition to its significance in growth and development, the insulin-like growth factor system also has important roles in a wide variety of pathological states. This has led to interest in the therapeutic potential of insulin-like growth factors and their binding proteins as candidate drug targets. This comprehensive book contains contemporary information on both basic science and clinical aspects of IGFs and their regulatory proteins, with emphasis on their relevance to cancer.

aintaining extracellular calcium concentrations within a narrow range is critical for the survival of most vertebrates. PTH, together with vitamin D, responds to hypocalcemia to increase extracellu­ M lar calcium levels, by acting on bone, kidney and intestine. The recent intro­ duction of PTH as a major therapeutic agent in osteoporosis has directed renewed interest in this important hormone and in the physiology of the parathyroid gland. The parathyroid is unique in that low serum calcium stimulates PTH secretion. As hypocalcemia persists, there is also an increase in PTH synthesis. Chronic hypocalcemia leads to hypertrophy and hyper­ plasia of the parathyroid gland together with increased production of the hormone. Phosphate is also a key modulator of PTH secretion, gene expres­ sion and parathyroid cell proliferation. Understanding the biology of the parathyroid as well as the mecha­ nisms of associated diseases has taken great strides in recent years. This book summarizes the molecular mechanisms involved in the function of the para­ thyroid gland. The first chapter reviews the development of the parathyroid gland and the genes involved in this process as identified using genetically manipulated mice. Then the biosynthetic pathway of PTH from gene ex­ pression to its intracellular processing and the sequences in the gene control­ ling its transcription as well as those regulating mRNA processing, stability and translation are described.

Protein Kinase C is a pivotal component of the mechanism that allows a cell to respond to its changing environment. In this book, the most significant advances in recent basic research on Protein Kinase C are explained by active researchers in the field. The first seven chapters provide a comprehensive account of the fundamental structural and biochemical properties of Protein Kinase C. The remaining chapters contain overviews of the function of Protein Kinase C, both in lower organisms and in mammalian cells, the latter with a focus on immune cells and nerve cells. This book is the only recent publication devoted entirely to Protein Kinase C and forms a major point of reference for those active in the field. In addition it will appeal to those with a general interest in biochemistry, cell biology, immunology and neurobiology.

As the first comprehensive overview of the nucleolus since 1985, The Nucleolus covers our current understanding of the cell nucleolus, including its role in ribosome assembly and its additional newly-discovered activities. The eighteen chapters have been written by experts who are actively engaged in research on the nucleolus and have an in depth review of the following topics: - nucleolar ultrastructure and dynamics, - behavior during mitosis, - ribosomal DNA gene and chromatin structure, - pre-ribosomal RNA transcription, - processing and modification, - ribosome assembly, - small nucleolar RNAs, - proteomics and non-traditional functions of the nucleolus.Separate chapters are also provided for yeast and higher eukaryotes on many topics. The Nucleolus will appeal not only to scientists directly engaged in nucleolar research, but also those working in related areas such as gene expression, protein biosynthesis, ribosome structure, transcription, chromatin structure, molecular genetics and the structure and functions of the cell nucleus in general.

Eukaryotic DNA Damage Surveillance and Repair contains chapters from experts in the field of DNA damage detection, repair, and cell cycle control. The work reviews current understanding of how different types of DNA damage are detected and focuses on how these surveillance mechanisms are coupled to processes of DNA repair, cell cycle control, and apoptosis. The title will be of interest to undergraduate/postgraduate students and academics alike.

The Biogenesis of Cellular Organelles represents a comprehensive summary of recent advances in the study of the biogenesis and functional dynamics of the major organelles operating in the eukaryotic cell. This book begins by placing the study of organelle biogenesis in a historical perspective by describing past scientific strategies, theories, and findings and relating these foundations to current investigations. Reviews of protein and lipid mediators important for organelle biogenesis are then presented, and are followed by summaries focused on the endoplasmic reticulum, Golgi, lysosome, nucleus, mitochondria, and peroxisome.

Members of the Rho family of small GTP-binding proteins (GTPases) are key signal transduction proteins that mediate signals initiated by growth factors, cytokines and cell adhesion proteins. Our knowledge about Rho GTPases has rapidly expanded over the past several years and Rho GTPases is the first book to provide a comprehensive overview of the regulation and functions of this important class of proteins. This book includes several chapters dedicated to the review of various classes of proteins that control the localization and activation state of Rho GTPases. Additional chapters discuss the wide range of biological functions that are controlled by Rho GTPases, including the organization of the actin cytoskeleton, cell proliferation and cell motility. Rho GTPases is essential reading for cell and molecular biologists, biochemists and geneticists. The critical roles of Rho family members in cancer and inflammatory diseases makes Rho GTPases also an invaluable guide for clinical investigators and pharmacologists.

Viral Genome Packaging focuses on the process of genome "packaging" within a pre-formed viral procapsid. The chapters of this book concentrate on the biochemistry, enzymology and structural aspects of the genome packaging machinery. This book defines a broad mechanistic basis for the process across the prokaryotic and eukaryotic border, and for DNA and RNA viruses. The biochemical, biophysical and structural aspects of genome packaging are examined in detail.

In the early 1980s, a few scientists started working on a Xenopus transcription factor, TFIIIA. They soon discovered a novel domain associated with zinc, and named this domain "zinc finger. " Th e number of proteins with similar zinc fingers grew quickly and these proteins are now called C2H2, Cys2His2 or classical zinc finger proteins. To date, about 24,000 C2H2 zinc finger proteins have been recognized. Approximately 700 human genes, or more than 2% of the genome, have been estimated to encode C2H2 finger proteins. From the beginning these proteins were thought to be numerous, but no one could have predicted such a huge number. Perhaps thousands of scientists are now working on C2H2 zinc finger proteins fi-om variou s viewpoints. This field is a good example of how a new science begins with the insight of a few scientists and how it develops by efforts of numerous independent scientists, in contrast to a policy-driven scientific project, such as the Human Genome Project, with goals clearly set at its inception and with work performed by a huge collaboration throughout the world. As more zinc finger proteins were discovered, several subfamilies, such as C2C2, CCHC, CCCH, LIM, RING, TAZ, and FYVE emerged, increasing our understanding of zinc fingers. The knowledge was overwhelming. Moreover, scientists began defining the term "zinc finger" differently and using various names for identical zinc fingers. These complications may explain why no single comprehensive resource of zinc finger proteins was available before this publication.

Selective Sweep deals with the theory and practice of detection of recent adaptive evolution at the genomic level from the patterns of DNA polymorphism. Recent advances in genomic sequencing provide the background for analysis of polymorphic sites in large chromosomal regions or even in whole genome, thus providing the tool for effective identification of loci that are under strong pressure of positive selection. For this reason, the studies of selective sweep, which formerly were of interest mostly to evolutionists, have become widely recognized and appreciated by the large biological community involved in identification of the targets of selection during speciation, host/pathogen interactions, and resistance to chemical agents.

This book will be of undoubted value to biomedical students and teachers, as well as those actively engaged in research on cholesterol metabolism, cancer, and atherosclerosis.

Toll Receptors and the Renaissance of Innate Immunity Elizabeth H. Bassett and Tina Rich Overview n the last few pages of Immunology: The Science of Self-Nonself Discrimination Jan Klein ponders on what he would study if he were to start over in the lab. ^ Dismissing the I antibody, MHC, the T-cell and parasitology, he considers instead the phylogeny of immune reactions, particularly in ancient phyla. As for a favored cell he chooses the macrophage. Describ­ ing it as a ^^MddchenfUr alles," (all purpose kitchen maid) Klein believed that this immunocyte still had secrets to reveal. Toll-Like Receptor (TLR) biology would prove to be one of these secrets. Analyses of the evolution of these receptors (Tolls and TLRs) have also helped us to rethink immune system phylogeny. In the first part of this chapter the history of the discovery of Toll and TLR biology is described. The evolution of the TLR genes and theories of immune function are covered in later sections. The remainder of this book presents work from nine groups active in the field. In the first chapter, "The Function of Toll-Like Receptors", Zlatko Dembic sets the stage by introducing us to many of the components of the immune system and their relationships vis a vis Toll receptors. Zlatko finishes his chapter with a discussion about current immune system models and contributes his own 'integrity model'. Work from the laboratory of Nicholas Gay follows this in "Structures and Motifs Involved in Toll Signaling".