Microarrays for simultaneous measurement of redundancy of RNA species are used in fundamental biology as well as in medical research. Statistically, a microarray may be considered as an observation of very high dimensionality equal to the number of expression levels measured on it. In "Statistical Methods for Microarray Data Analysis: Methods and Protocols, " expert researchers in the field detail many methods and techniques used to study microarrays, guiding the reader from microarray technology to statistical problems of specific multivariate data analysis. Written in the highly successful "Methods in Molecular Biology " series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory.

Thorough and intuitive, "Statistical Methods for Microarray Data Analysis: ""Methods and Protocols "aids scientists in continuing to study microarrays and the most current statistical methods.

For more than a century, microscopy has been a centerpiece of extraordinary discoveries in biology. Along the way, remarkable imaging tools have been developed allowing scientists to dissect the complexity of cellular processes at the nano length molecular scales. Nanoimaging: Methods and Protocols presents a diverse collection of microscopy techniques and methodologies that provides guidance to successfully image cellular molecular complexes at nanometer spatial resolution. The book's four parts cover: (1) light microscopy techniques with a special emphasis on methods that go beyond the classic diffraction-limited imaging; (2) electron microscopy techniques for high-resolution imaging of molecules, cells and tissues, in both two and three dimensions; (3) scanning probe microscopy techniques for imaging and probing macromolecular complexes and membrane surface topography; and (4) complementary techniques on correlative microscopy, soft x-ray tomography and secondary ion mass spectrometry imaging. Written in the successful format of the Methods in Molecular Biology (TM) series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Nanoimaging: Methods and Protocols highlights many of the most exciting possibilities in microscopy for the investigation of biological structures at the nano length molecular scales.

Quantitative Real-Time PCR: Methods and Protocols focuses on different applications of qPCR ranging from microbiological detections (both viral and bacterial) to pathological applications. Several chapters deal with quality issues which regard the quality of starting material, the knowledge of the minimal information required to both perform an assay and to set the experimental plan, while the others focus on translational medicine applications that are ordered following an approximate logical order of their medical application. The last part of the book gives you an idea of an emerging digital PCR technique that is a unique qPCR approach for measuring nucleic acid, particularly suited for low level detection and to develop non-invasive diagnosis. Written for the Methods in Molecular Biology series, most chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, laboratory protocols and tips on troubleshooting and avoiding known pitfalls. Practical and authoritative, Quantitative Real-Time PCR: Methods and Protocols aims to aid researchers seeking to devise new qPCR-based approaches related to his or her area of investigation.

Membrane proteins play a key role in numerous pathologies such as cancer, cystic fibrosis, epilepsy, hyperinsulinism, and Alzheimer s disease, yet studies on these and other disorders are hampered by a lack of information about the proteins involved. In Heterologous Expression of Membrane Proteins: Methods and Protocols, expert researchers provide an overview of the different heterologous expression systems available to produce these proteins for structural analysis, helping us to understand how these proteins function, and additionally, how their functions can be modified through drug treatment. Chapters examine membrane protein solubilization, purification, and instability in solution, and investigate the strategies that helped to determine the structure of the first heterologously expressed mammalian membrane proteins. Composed in the highly successful Methods in Molecular Biology series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls.

Far-reaching and innovative, Heterologous Expression of Membrane Proteins: Methods and Protocols, is an essential guide for novice and experienced researchers alike, providing detailed methods for existing expression systems alongside cutting-edge strategies for future use in the field."

Computational biology is an interdisciplinary field that applies mathematical, statistical, and computer science methods to answer biological questions, and its importance has only increased with the introduction of high-throughput techniques such as automatic DNA sequencing, comprehensive expression analysis with microarrays, and proteome analysis with modern mass spectrometry. In Computational Biology, expert practitioners present a broad survey of computational biology methods by focusing on their applications, including primary sequence analysis, protein structure elucidation, transcriptomics and proteomics data analysis, and exploration of protein interaction networks. As a volume in the highly successful Methods in Molecular Biology (TM) series, this work provides the kind of detailed description and implementation advice that is crucial for getting optimal results. Authoritative and easy to use, Computational Biology is an ideal guide for all scientists interested in quantitative biology.

This book reviews a novel and exciting field of cellular and molecular biology called epitranscriptomics, which focuses on changes in an organism's cells resulting from the posttranscriptional modification of cellular RNA. RNA-binding proteins (RBPs) play a crucial role in these posttranscriptional modifications and also support several cellular processes necessary for maintaining RNA homeostasis. Exploring the mechanisms underlying RNA modifications and RBP function is an emerging area of biomedical research, taking the study of gene regulation a step beyond epigenetics. This book reveals that the RNA molecule is not just an information-carrying molecule with some secondary structures. Accordingly, how RNA is modified, regulated, packaged, and controlled is an important aspect. Leading experts address questions such as where the over 170 distinct posttranscriptional RNA modifications are located on the genome, what percentage of mRNAs and noncoding RNAs these modifications include, and how an RNA modification impacts a person's biology. In closing, the book reviews the role of RNA modifications and RBPs in a variety of diseases and their pathogenesis. Addressing some of the most exciting challenges in epitranscriptomics, this book provides a valuable and engaging resource for researchers in academia and industry studying the phenomena of RNA modification.

The observation that neuropeptide Y (NPY) is the most abundant peptide present in the mammalian nervous system and the finding that it elicits the most powerful orexigenic signal have led to active investigations of the properties of the NPY family of hormones, including peptide YY (PYY) and pancreatic polypeptide (PP). Nearly two decades of research have led to the identification of several NPY receptor subtypes and the development of useful receptor selective ligands. Moreover, these investigations have imp- cated NPY in the pathophysiology of a number of diseases, including feeding disorders, seizures, memory loss, anxiety, depression, and heart failure. Vigorous efforts are therefore continuing, not only to understand the bioche- cal aspects of NPY actions, but also toward developing NPY-based treatments for a variety of disorders. To facilitate these efforts, it was decided to produce the first handbook on NPY research techniques as part of the Methods in Molecular Biology Series. In compiling Neuropeptide Y Protocols, I have gathered contributions on techniques considered critical for the advancement of the NPY field from experts in various disciplines. Each chapter starts with a brief introduction, with Materials and Methods sections following. The latter sections are presented in an easy to follow step-by-step format. The last section of the chapter, Notes, highlights pitfalls and the maneuvers employed to overcome them. This information, not usually disseminated in standard research pub- cations, may prove extremely useful for investigators employing these te- niques in NYP research.

Nuclear Receptors focuses on the structural analysis of nuclear receptors from the initial work using isolated protein domains to the more recent exciting developments investigating the conformational shape of full-length receptor complexes. The book also reviews the structure of key nuclear receptor co-regulatory proteins. It brings together, for the first time, a comprehensive review of nuclear receptor structure and the importance of receptor conformation underpinning allosteric regulation by different ligands (hormone, drugs, DNA response elements, protein-protein interactions) and receptor activity. The nuclear receptor superfamily, including receptors for steroid hormones and non-steroid ligands, are pivotal to normal physiology, regulating processes as diverse as reproduction, metabolism, the immune system and brain development. The first members of the family were cloned over 25 years ago, which heralded in the idea of a superfamily of intracellular receptor proteins that bound small molecule ligands: classical steroid hormones, vitamins, fatty acids and other products of metabolism. These signals are then transmitted through multiprotein receptor-DNA complexes, leading to the regulation of target genes, often in a cell-selective manner. The cloning of the receptor cDNAs also ushered in an era of unparalleled analysis of the mechanisms of action of these ligand-activated transcription factors.

Cell to Organ: Electromechanical Activation.- 1 Regulation of Intracellular Calcium in Cardiac Muscle.- 2 Neuromodulation of Calcium Current by Extracellular ATP in Isolated Ventricular Myocytes.- 3 Intracellular Calcium and Myocardial Function during Ischemia.- 4 Intracellular Signaling in Vascular Smooth Muscle.- 5 Myocardial Energetics.- 6 Mechanisms of Endocardial Endothelium Modulation of Myocardial Performance.- 7 Calcium Kinetic and Mechanical Regulation of the Cardiac Muscle.- 8 Cellular Responses to Electrical Stimulation: A Study Using a Model of the Ventricular Cardiac Action Potential.- 9 Excitation-Contraction Coupling and Contractile Protein Function in Failing and Nonfailing Human Myocardium.- Mechanics and Microcirculation.- 10 Estimation of Myocardial Mechanical Properties with Dynamic Transverse Stiffness.- 11 Intramyocardial Mechanical States: Vessel-Interstitium-Muscle Interface.- 12 Myocardial Mechanics and Coronary Flow Dynamics.- 13 Modeling of Coronary Capillary Flow.- Microstructure: Mechanics and Microcirculation.- 14 Models for Coronary Pressure-Flow Relationships.- 15In VivoMyocardial Microcirculation: Evaluation with a Whole-Body X-Ray CT Method.- 16 Endocardial Coronary Microcirculation of the Beating Heart.- 17 Distribution and Control of Coronary Microvascular Resistance.- 18 Theoretical Analysis of Coronary Blood Flow and Tissue Oxygen Pressure-Control.- Microcirculation and Metabolic Transport.- 19 Adenosine Coronary Vasodilation during Hypoxia Depends on Adrenergic Receptor Activation.- 20 Chaos in Cardiac Signals.- 21 Intramyocardial Fluid Transport Effects on Coronary Flow and Left Ventricular Mechanics.- 22 Metabolic Protection of Post-Ischemic Phosphorylation Potential and Ventricular Performance.- 23 Metabolic and Mechanical Control of the Microcirculation.- Remodeling of Muscle and Vessels.- 24 Asymmetrical Changes in Ventricular Wall Mass by Asynchronous Electrical Activation of the Heart.- 25 Ventricular Remodeling after Myocardial Infarction.- 26 Arterial Remodelling after Percutaneous Transluminal Balloon Angioplasty.- 27 Structural and Functional Remodeling of Poststenotic Arteries in the Rat.- 28 Myocardial Collagen and Its Functional Role.- Cardiac Function and Circulation.- 29 Ventricular-Arterial Interaction: Cardiac Effects of Mean versus Pulsatile Arterial Load.- 30 The Veins and Ventricular Preload.- 31 Why Smaller Animals Have Higher Heart Rates.- 32 Feedback Effects in Heart-Arterial System Interaction.- Integrated Analysis.- 33 The Relationship between Altered Load and Impaired Diastolic Function in Conscious Dogs with Pacing Induced Heart Failure.- 34 Interactions: The Integrated Functioning of Heart and Lungs.- 35 Carotid-Cardiac Interaction: Heart Rate Variability during the Unblocking of the Carotid Artery.- 36 Right and Left Ventricle Interaction and Remodeling in Congenital Heart Disease.- 37 Macroscopic Three-Dimensional Motion Patterns of the Left Ventricle.- 38 Cardiovascular Flow Velocity Measurements by 2D Doppler Imaging for Assessment of Vascular Function.- The Editors.- Contributors.

Understanding an individual's genetic makeup is the key to creating personalized drugs with greater efficacy and safety, and pharmacogenomics aims to study the complex genetic basis of inter-patient variability in response to drug therapy. Based upon the success of its first edition, the second edition of Pharmacogenomics: Methods And Protocols aims to continue providing readers with high-quality content on the most innovative and commonly adopted technologies in the field of pharmacogenomics as presented by experts in the field. Broken into several sections, this detailed volume examines techniques for interrogating variation in human genes and genomes, functional assessment of genetic variation, both in vitro and in vivo, as well as tools for translation and implementation of pharmacogenetic markers. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to the respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Comprehensive and thoroughly updated, Pharmacogenomics: Methods And Protocols, Second Edition serves as an essential reference and an invaluable source on the latest information in this field.

A compendium of readily reproducible and novel methods to manipulate DNA viruses and characterize their varied biological properties. The authors emphasize techniques for viral detection and genetics, but also include methods for structure determination, gene expression, replication, pathogenesis, complex cellular models, recombinant genetics, and computational/systems approaches. Wide-ranging and highly practical, DNA Viruses: Methods and Protocols will stimulate new directions in virology research with its novel strategies for engineering viral vectors in gene therapy, and its advanced approaches for detecting viruses in human disease.

Infectious diseases caused by bacteria remain a leading cause of death worldwide. Many of the antibiotics developed to combat bacterial infections have been rendered almost impotent due to the rapid evolution and spread of antibiotic resistance. A common and major resistance mechanism, the efflux system, enables bacteria to extrude structurally divers antimicrobials, facilitating survival in toxic environments. This book reviews the most important current research and summarizes the most spectacular discoveries in the field.

Biochemical Pathways and Environmental Responses in Plants, Part A, Volume 676 in the Methods in Enzymology series highlights new advances in the field with this new volume presenting interesting chapters on topics such as Structure, function, and engineering of plant polyketide synthases, A sensitive LC-MS/MS assay for enzymatic characterization of methylthioalkylmalate synthase involved in glucosinolate side-chain elongation, Assaying formate-tetrahydrofolate ligase with monoglutamylated and polyglutamylated substrates using a fluorescence-HPLC based assay, An Approach to Nearest Neighbor Analysis of Pigmented Protein Complexes by Using Chemical Crosslinking in Combination with Mass Spectrometry, and much more. Other chapters cover Biochemical characterization of plant aromatic aminotransferases, Functional Analysis of Phosphoethanolamine N-methyltransferase (PMT) in Plants and Parasites, A structure-guided computational screening approach for predicting plant enzyme-metabolite interactions, Plant metacaspase: an example of microcrystal structure determination and analysis, Biocatalytic system for comparative assessment of functional association of cytochrome P450 monooxygenases with their redox partners, Dirigent Protein Family Function and Structure, and more.

Proteoglycans are some of the most elaborate macromolecules of mammalian and lower organisms. The covalent attachment of at least five types of glycosami- glycan side chains to more than forty individual protein cores makes these molecules quite complex and endows them with a multitude of biological functions. Proteoglycan Protocols offers a comprehensive and up-to-date collection of prepa- tive and analytical methods for the in-depth analysis of proteoglycans. Featuring st- by-step detailed protocols, this book will enable both novice and experienced researchers to isolate intact proteoglycans from tissues and cultured cells, to establish the composition of their carbohydrate moieties, to generate strategies for prokaryotic and eukaryotic expression, to utilize methods for the suppression of specific proteoglycan gene expression and for the detection of mutant cells and degradation products, and to study specific interactions between proteoglycans and extracellular matrix proteins as well as growth factors and their receptors. The readers will find concise, yet comprehensive techniques carefully drafted by leading experts in the field. Each chapter commences with a general Introduction, followed by a detailed Materials section, and an easy-to-follow Methods section. An asset of each chapter is the extensive notation that includes troubleshooting tips and practical considerations that are often lacking in formal methodology papers. The reader will find this section most valuable because it is clearly provided by experienced scientists who have first-hand knowledge of the techniques they outline. In addition, most of the chapters are well illustrated with examples of typical data generated with each method.

Transcriptome Profiling: Progress and Prospects assists readers in assessing and interpreting a large number of genes, up to and including an entire genome. It provides key insights into the latest tools and techniques used in transcriptomics and its relevant topics which can reveal a global snapshot of the complete RNA component of a cell at a given time. This snapshot, in turn, enables the distinction between different cell types, different disease states, and different time points during development. Transcriptome analysis has been a key area of biological inquiry for decades. The next-generation sequencing technologies have revolutionized transcriptomics by providing opportunities for multidimensional examinations of cellular transcriptomes in which high-throughput expression data are obtained at a single-base resolution. Transcriptome analysis has evolved from the detection of single RNA molecules to large-scale gene expression profiling and genome annotation initiatives. Written by a team of global experts, key topics in Transcriptome Profiling include transcriptome characterization, expression analysis of transcripts, transcriptome and gene regulation, transcriptome profiling and human health, medicinal plants transcriptomics, transcriptomics and genetic engineering, transcriptomics in agriculture, and phylotranscriptomics.

For bacteria ..."the times are achanging..". The genomes of over 60 different bacteria have now been sequenced, and we know a lot about the important research organism Escherichia coli, the important industrial organism Bacillus subtilis, and about important plant and human pathogens. It will not take long before we know all the gene products and their functions of a few of these bacteria. Some of us already begin to think about a digital model E. coli or Bacillus cell. For that end we need to know all the physiological activities and metabolic routes of the cell. But in addition we like to know how things work at the molecular level and how protein and membranes as well as other (macromolecular) structures work together to carry out specific cell functions.

Protein Secretion Pathways in Bacteria describes all the known folding and targeting routes of inner and outer membrane proteins as well as of proteins that are secreted by several specific export routes. The book gives detailed molecular information about the structures that are important for the different mechanisms involved. This is a valuable contribution to the understanding of how rather simple and yet complex bacterial cells work.

Plant secondary metabolism is an economically important source of fine chemicals, such as drugs, insecticides, dyes, flavours, and fragrances. Moreover, important traits of plants such as taste, flavour, smell, colour, or resistance against pests and diseases are also related to secondary metabolites. The genetic modification of plants is feasible nowadays. What does the possibility of engineering plant secondary metabolite pathways mean? In this book, firstly a general introduction is given on plant secondary metabolism, followed by an overview of the possible approaches that could be used to alter secondary metabolite pathways. In a series of chapters from various authorities in the field, an overview is given of the state of the art for important groups of secondary metabolites. No books have been published on this topic so far. This book will thus be a unique source of information for all those involved with plants as chemical factories of fine chemicals and those involved with the quality of food and ornamental plants. It will be useful in teaching graduate courses in the field of metabolic engineering in plants.

The in situ hybridization and PCR technologies are now well-established molecular techniques for studying chromosomal aneuploidy and rearran- ments, gene localization and expression, and genomic organization. Over the last decade, we have seen increasing applications in these fields. By combining the high sensitivity of the PCR reaction and the cytological localization of target sequences, both PRINS and in situ PCR techniques have provided highly powerful complements to FISH for in situ cellular and molecular investigations. Both these approaches have several advantages in terms of sensitivity and specificity, owing to the use of primers and to the fast kinetics of annealing and elongation reactions in situ. In the first edition of PRINS and In Situ PCR Protocols edited by John R. Gosden, experts in the field presented in detail a variety of applications of PRINS and in situ PCR techniques, in a wide range of clinical conditions. Since the publication of this successful reference book, there have been s- nificant improvements in in situ detection techniques. This completely revised and updated second edition presents a compreh- sive selection of new procedures developed in the field of PRINS and in situ PCR technologies. The book has two sections. Part I, Basic Methodology, contains chapters that provide useful protocols for many variations of PRINS and in situ PCR, including a new fast multicolor PRINS method, and protocols for PRINS detection of unique sequences in situ.

This volume explores the technological improvements in protein engineering, expression, purification, and crystallization of several rhodopsin photoactive intermediates, thus increasing our understanding of rhodopsin activation. The first chapters of the book focus on methods developed to study fundamentals of rhodopsin structure and function, starting with improved purification protocols of native and mutated rhodopsin, followed by methods used for rhodopsin reconstitution into lipid bilayers stabilizing rhodopsin function properties, and finally describing recently developed methods to study structural dynamics of rhodopsin activation and its mechanistic properties. Subsequently, chapters underline various techniques that have been developed to visualize the rhodopsin dimer and to study its functional significance. The next few chapters highlight cutting-edge imaging techniques of photoreceptors, rhodopsin trafficking, and its diffusion within signaling membranes. Finally the book concludes with recent developments that could be potentially beneficial in patient treatments, and treatment strategies for retinal degenerative diseases. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Timely and practical, Rhodopsin: Methods and Protocols reaches out to researchers and health practitioners, and provides timely protocol useful for studying structural and functional properties of rhodopsin.

Human Microbiome in Health and Disease, Volume 191, Part A presents updated knowledge on human microbiome as covered by renowned science faculty across the globe. Chapters in this volume include an introduction to human microbiome, Structure, functions and diversity of healthy human microbiome, Role of human microbiome in cancer, Gut microbiota and gastrointestinal cancer, Dysbiosis of human microbiome and metabolic diseases, Gut microbiome and type 2 diabetes, Gut microbiome and non-alcoholic fatty liver disease, Hepatic drug metabolism and intestinal microbiota, Emerging tools for understanding the human microbiome, and Microbiome therapeutics: Opportunity and challenges, and more. These chapters cover the composition, diversity, dynamics and functions of human microbiome in health and disease. This book will form an excellent and informative text on keystone, autochthonous, and exogenous microbiota important for human health in a simple to understand and easy to read format.

Legionellosis is a disease of significant medical and public interest. Legionella is commonly found in aquatic habitats where its ability to survive and to multiply within different protozoa equips the bacterium to be transmissible and pathogenic to humans. In addition, Legionella has become a favored model system to analyze the mechanisms of bacterial survival, acquisition of nutrients, and intracellular replication. Following the recent publication of the genome sequences of four L. pneumophila strains, it is now feasible to investigate the whole genome in silico, the transcriptome via micro arrays, and the proteome by two-dimensional gel electrophoresis. Research in the fields of clinical features, diagnosis, treatment, and epidemiology continues to generate new data. The topics covered by this volume range from the history of the identification of Legionella and clinical disease treatment, to the microbe's gene expression and secretion systems, as well as its strategies for intracellular multiplication and nutrient acquisition. The main focus of the book is the current state of many of the most critical features of Legionella. Internationally renowned authors have contributed chapters describing and discussing the latest research findings with an emphasis on molecular aspects. The editors and authors have produced an excellent book that will be an extremely useful reference source. This comprehensive publication is aimed at readers with teaching or research interests in microbiology, genetics, genomics, infectious diseases, or clinical research.

Direct cell-cell communication is a common property of multicellular organisms that is achieved through membrane channels which are organized in gap junctions. The protein subunits of these intercellular channels, the connexins, form a multigene family that has been investigated in great detail in recent years. It has now become clear that, in different tissues, connexins speak several languages that control specific cellular functions. This progress has been made possible by the availability of new molecular tools and the improvement of basic techniques for the study of membrane channels, as well as by the use of genetic approaches to study protein function in vivo. More important, connexins have gained visibility because mutations in some connexin genes have been found to be linked to human genetic disorders. Connexin Methods and Protocols presents in detail a collection of te- niques currently used to study the cellular and molecular biology of connexins and their physiological properties. The field of gap junctions and connexin research has always been characterized by a multidisciplinary approach c- bining morphology, biochemistry, biophysics, and cellular and molecular biology. This book provides a series of cutting-edge protocols and includes a large spectrum of practical methods that are available to investigate the fu- tion of connexin channels. Connexin Methods and Protocols is divided into three main parts.

Studies on stem cells have been attracting intense scientific and p- lic attention, not only because of controversies surrounding the use of embryonic stem cells but also because of very provocative data that have been emerging on adult stem cells. Much of the public attention and debate has been focused on the possibility that adult stem cells may be used as a substitute for human embryonic stem cells or as a justification for stopping work on them. This has somewhat dim- ished attention on very heated scientific debates that take us to the very heart of how the concept of stem cells is perceived. To this author, the latter debates have not been unlike certain philosophical debates of the last century. Since the seminal studies of Till and McCulloch in the 1960s, the popular paradigm on adult stem cells has been that lineage-restricted stem cells are derived from pluripotent stem cells very early during development. To many, and consistent with much data, the restriction to particular lineages was considered absolute. In other words, there was a sense of determinism in the stem quality of particular stem cells: once they were allocated, they were programmed to specific roles in a given tissue. Furthermore, some adult tissues were considered devoid of detectable stem cell presence or activity.

After a decade of dominance by recombinant DNA technology, the field of molecular and cell biology is witnessing a renewed interest in techniques and approaches that are not driven by DNA acrobatics. In hindsight, this is an inevitable outcome. Deoxyribonucleic acid is not the master; it is only a storage house. If one wishes to know how cells work, the secret is not to be found in DNA, but rather in everything outside DNA. Science based on DNA is useful but does not itself solve the problem. It is most fortunate that at the height of the DNA phenomenon, there remain scientists who continue to probe cells by non-DNA means. Suddenly, people with such expertise are in high demand.
In this volume, some truly original scientists take the time to tell us their stories of innovations-some almost iconoclastic. All of these researchers have pioneered approaches that were long neglected; moreover, each is now in the fruitful phase of great harvests. It is a wonderful lesson for graduate students and postdoctorates that, although not being in the pack might be risky, the reward of such work is sweeter. As in physics, biology needs more young people who think like Richard Feynman - the ultimate iconoclast.
On the surface, the eight chapters of this volume appear to be diverse, but they are not. If our purpose is to understand cells, we must stop the habit of constantly dissecting leaves. Once in a while we have to see which forest we are in. The contributions included herein cannot cover the whole cell, but they give a sufficient flavor to arouse a desire to think more globally about cells. At a time when our field is in danger of being buried by thousands of kinases and phosphatases, these chapters inform our intended audiences that there are other ways - other techniques, other approaches, other thinkings, and other stories. We need all of them to appreciate the holistic aspect of cells, which has been a taboo until now.

Microbial toxins are secondary metabolites that accumulate in the organism and, to a large extent, are metabolically inactive towards the organism that produces them. The discovery of penicillin, a secondary metabolite of Penicillium notatum West (= P. chrysogenum Thom), in 1929 marked a milestone in the development of antibiotics (microbial toxins). In the intensive studies that followed this discovery, scientists chemically characterized several new molecules (toxins) from secondary metabolites of microbes, some having a definite function in causing pathogenesis in plants. Toxins are also known to playa significant role in inciting animal (human) and insect diseases and as plant growth regulators. Many common toxins have also been isolated from different microbes exhibiting a wide spectrum of biological activity. Toxins are broadly divisible into several characteristic groupings - polyketides, oxygen heterocyclic compounds, pyrons, terpenoidS, amino acids - diketopiperazines, polypeptides etc. Recent research has indicated that these toxins play an important role in plant pathogenesis, disease epidemics, plant breeding, biological control of plant pathogens and insect pests, induced resistance, plant-pathogen interactions etc. Toxins produced by weed pathogens are exploited as lead molecules in developing environmentally friendly herbicides.