Approaches to the recovery of three-dimensional information on a biological object, which are often formulated or implemented initially in an intuitive way, are concisely described here based on physical models of the object and the image-formation process. Both three-dimensional electron microscopy and X-ray tomography can be captured in the same mathematical framework, leading to closely-related computational approaches, but the methodologies differ in detail and hence pose different challenges. The editors of this volume, Gabor T. Herman and Joachim Frank, are experts in the respective methodologies and present research at the forefront of biological imaging and structural biology. Computational Methods for Three-Dimensional Microscopy Reconstruction will serve as a useful resource for scholars interested in the development of computational methods for structural biology and cell biology, particularly in the area of 3D imaging and modeling.

Filamentous fungi have long been known for their ability to produce an enormous range of unusual chemical compounds known as secondary metabolites, many of which have potentially useful antibiotic or pharmacological properties. Recent focus on fungal genomics coupled with advances in detection and molecular manipulation techniques has galvanized a revitalization of this field. Fungal Secondary Metabolism: Methods and Protocols is aimed at providing the key methodologies currently in use and necessary for accessing and exploiting the natural product information provided by the genomes of this large and varied kingdom. Written by active researchers in the field, the chapters deal with all the steps necessary, from optimization of fungal culture conditions for metabolite production, through rapid genome sequencing and bioinformatics, and genetic manipulations for functional analysis, to detection and testing of metabolites. In addition, chapters on basic science address approaches to the genetic regulation, protein biochemistry, and cellular localization of the biosynthetic pathways. Written in the highly 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 laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and hands-on, Fungal Secondary Metabolism: Methods and Protocols encourages new investigators to enter the field and expands upon the expertise and range of skills of those already researching fungal natural products.

The immune system is a complex network in which different cell types and soluble factors interact to efficiently eliminate various kinds of microorganisms as well as aberrant cell clones. The roots of immunologic investigations reach far into the past. In 430 BC, Thucydides reported that survivors of the plague did not present a second time with similar symptoms. The first report of a successful immu- therapy was made by Edward Jenner in 1798 who found a protective effect of cowpox vaccination against human pox. Since then, much knowledge has been accumulated; today, investigations of the molecular mechanisms of immune regulation are of central research interest. The novel insights into gene polymorphisms and gene regulation gathered from this work has improved our knowledge of individual immune reactions and risk factors in overcoming infections. Strategies to use the immune system for cancer treatment have been propelled by the discovery of divergent immunoregulatory cytokines and the introduction of new gene therapy strategies to modify immune responses. Recently, the discovery of various dendritic cells has focused attention on these cell types as central elements of the immune response and to the possibility of dendritic cell expansion, maturation, and consecutive stimulation with immuno- active tumor-specific peptides. Similarly, methods for ex vivo expansion of various stem cell-derived cell types have led to an improved therapeutic management of various benign and malignant diseases.

Molecular farming has been hailed as the "third wave" of genetically-modified organisms produced through biotechnology for the bio-based economy of the future. Unlike products of the first wave, such as herbicide resistant crop plants, which were perceived to benefit only the farmers who used them and the agrochemical companies who developed them, products of molecular farming are designed specifically for the benefit of the consumer. Such products could be purified from food or non-food organisms for a range of applications in industry, as well as animal and human health. Alternatively, the products of this technology could be consumed more directly in some edible format, such as milk, eggs, fruits or vegetables. There is a rapidly-growing interest Qn the part of the public as well as in the medical community in the role food plays in health, especially in the immunophysiological impact of food over and above the role of basic nutrition.

Pulmonary embolism is a common but vexing illness. This book provides a contemporary overview of the most important issues from a Western and a Japanese perspective, providing the reader with state-of-the-art knowledge of the epidemiology and molecular biology of the disease. In the Diagnosis section, the relationship between venous thrombosis and pulmonary embolism is explored, and exciting new findings are presented in the fields of echocardiography and magnetic resonance imaging. The Management section focuses on surgical intervention with acute embolectomy as well as updating thromboendarterectomy for chronic pulmonary embolism. The importance of primary and secondary prevention is emphasized in chapters addressing low molecular weight heparin and the inferior vena cava filter. This cutting-edge book is a valuable resource for practicing physicians, researchers, and students in internal medicine, hematology, pulmonary critical care, and vascular medicine.

The genome sequences of several pseudomonads have become available in recent years and researchers are beginning to use the data to make new discoveries about this bacterium. This concise volume reviews the most current and topical aspects of Pseudomonas molecular biology and genomics and is aimed at a readership of research scientists, graduate students and other specialists. Renowned international authors have contributed chapters on diverse topics including taxonomy, genome diversity, oligonucleotide usage, polysaccharides, pathogenesis, virulence, biofilms, antibiotic resistance and iron uptake. In addition an entire chapter is devoted to the genetic tools being developed to take full advantage of the wealth of information generated by the genome sequencing efforts. This book is essential reading for anyone involved in Pseudomonas research.

Complex molecular mechanisms involving microbiology and immunology define the host-pathogen relationship. These mechanisms can be the basis for new drugs and vaccine design. 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. knowledge of bacteria-host cell interactions will be acquired fast enough to find the necessary tools for controlling microorganism development. This comprehensive book should appeal to scientists interested in cell biology, microbiology and immunology, as well as to clinically-oriented investigators concerned with infectious diseases.

This volume is divided in four sections; covering genome wide approaches, techniques for characterize of paRNA structural features are described, selecting pa-RNA, and paRNA therapeutic potential. Chapters describe how siRNAsdirected against paRNAs can be applied in vivo to modulate transcription of important genes controlled by paRNAs. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Promoter Associated RNA: Methods and Protocols aims to demonstrate paRNAs as new class of regulatory molecules, to further investigate and value as tools for fine transcriptional tuning.

sCongenital heart disease is the leading cause of infant death and affects approximately one in every 100 babies born in the United States. The study of cardiovascular development has acquired new momentum in last twenty years due to the advancement of modern molecular biology and new available equipments and techniques. In Cardiovascular Development: Methods and Protocols expert researchers in the field in the field detail many of the methods which are now commonly used in the field of cardiovascular development research. These include methods and technique for using different organisms for cardiovascular developmental research, using cell and molecular biology methods to study cardiovascular development, as well as other available techniques for cardiovascular development research. Written in the highly 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 laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Cardiovascular Development: Methods and Protocols seeks to aid scientists in understanding new state-of-the-art techniques in the field of cardiovascular development research including in vivo imaging and Bioinformatics.

In Osteoporosis and Osteoarthritis expert investigators detail modern tools to enhance discovery in bone and cartilage biology and promote translational research in osteoporosis and osteoarthritis. New chapters describe methods to generate induced pluripotent stem cells, perform high-throughput chromatin analysis, assess loads on bone cells in vivo and in vitro, use state-of-the art imaging techniques to measure articular cartilage thickness and biochemical properties, and establish animal models of osteoarthritis and bone healing. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their 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. Authoritative and practical, Osteoporosis and Osteoarthritis shares successful techniques that can be applied to the study of either disease.

ZIP Metal Ion Transporters, Volume 684 in the Methods in Enzymology series, highlights new advances in the field with this new volume presenting interesting chapters on a variety of topics, including Biochemistry, Biophysics and Structural Biology, Structure determination of a bacterial ZIP in lipidic cubic phase, Cell-based metal transport assay for animal and plant ZIPs, Measurement of metal binding affinity and transport activity in ZIP transporters using spectroscopic methods, Considerations in production of the (prokaryotic) ZIP family transporters for structural and functional studies, Metal-protein interactions investigated using model systems: thermodynamic, spectroscopic and computational methods, and more. Additional chapters cover Getting Zinc Into and Out of Cells, In-silico modeling of ZIP9 (TBD), Cellular Function and Regulation, Methods to visualize zinc transporter proteins of the SLC39A family in cells, Assessing metal ion transporting activity of ZIPs: intracellular zinc and iron detection, In vitro studies for studying manganese transport and homeostasis, and much more.

Molecular Sieves- Science and Technology will cover, in a comprehensive manner, the science and technology of zeolites and all related microporous and mesoporous materials. Authored by renowned experts, the contributions will be grouped together topically in such a way that each volume of the book series will be dealing with a specific sub-field. Volume 3 deals with the most widely employed techniques for the post-synthesis modificaton of molecular sieves. Among the topics covered in considerable detail are ion exchange, both in the more conventional variant in aqueous suspension and in the solid-state variant, the various methods for dealumination of zeolites, and the techniques for introducing metallic, ionic, oxidic and sulfidic clusters into the cages and channels of microporous materials.

Alzheimer's disease is the most common cause of senile dementia. Since the discovery in 1984 of the amyloid ?-peptide (A?) as the core protein of the senile plaques present in the brains of Alzheimer's disease sufferers, an immense amount of research has gone into mapping out the molecular basis of this debilitating disease. The aim of Alzheimer's Disease: Methods and Protocols is to bring together the main biochemical, cell biological, and molecular biological techniques and approaches that are being used to investigate the molecular basis of Alzheimer's disease. This volume begins with chapters of an introductory/ review nature. Chapter 1 provides a historical introduction to Alzheimer's d- ease with particular emphasis on the central role played by A? and its re- tion to tau. Chapter 2 examines the genetics underlying this neurodegenerative disease, covering the amyloid precursor protein, apolipoprotein E, and the presenilins. Chapter 3 presents an overview of currently available therapeutic agents and prospects for drugs of the future.

In the last 10 years researchers have firmly established key roles for R- related GTPases in almost every aspect of cell biology. In the 1980s the pro- oncogene Ras itself was the focus of interest, though in the 1990s this shifted to the increasing variety of Ras-related proteins. In this new decade much yet needs to be done to establish the role for all the small GTPases now uncovered by the human genome project. In particular, these GTPases need to be und- stood in the appropriate biochemical and cellular contexts. In the process of trying to uncover the role of these versatile proteins, a variety of novel te- niques and methodologies has been developed. These now enable investi- tors to move easily within a diversity of fields ranging from structural studies to real-time in vivo analysis of a GTPase. In recognition of the need for access to key background methodologies, GTPase Protocols: The Ras Superfamily is devoted to techniques that are pr- ently widely used and that will continue to be the standard for researchers worldwide. Each chapter is aimed at supplying detailed methodologies to allow reproduction in any laboratory, while also providing the general pr- ciples on which the methods are based. Some of the techniques grouped in the first section apply broadly to small GTPases, whereas others in Part II are more applicable within each GTPase subfamily.

The last few years have seen an explosion of new information and resources in the areas of plant molecular genetics and genomics. As a result of developments such as high throughput sequencing, we now have huge amounts of information available on plant genes. But how does this help people charged with the task of improving crop species to create products with altered functions or improved characteristics? This volume considers ways in which the new information, resources and technology can be exploited by the plant breeder. Examples in current use will be quoted wherever possible.

The incentive for putting together Volume 4 of this series was to review the wealth of new information that has become available in prokaryotic organisms in protein export and membrane biogenesis. Just in the last several years, protein translocation has now been efficiently reconstituted using defined components and the mechanism by which proteins are moved across membrane bilayers is now being examined at a higher resolution. In addition, because of a new technical breakthrough using osmolytes, it is now possible to reconstitute a number of channel proteins, ATPase, receptors, and transporters. In many cases, it is possible to successfully predict the membrane topology of these types of proteins using both "hydrophobicity analysis" and the "positive inside" rule.
In this volume, two chapters focus on protein translocation across membranes ("Biochemical Analyses of Components Comprising the Protein Translocation Machinery of E. Coli; Protein Translocation Genetics"), while several others on how proteins assemble into the ineer membrane of E. Coli ("Membrane Protein Assembly; Membrane Insertion of Small Proteins: Evolutionary and Functional Aspects; Pigment-Protein Complex Assembly in Rhodobacter sphaeroides and Rhodobacter Capsulatus"). Other sections review recent progress on transporters ("Identification and Reconstitution of Anion Exchange Mechanisms in Bacteria; Helic Packing in the C-Terminal Half of Lactose Permease") and signal transduction ("Mechanism of Transmembrane Signaling in Osmoregulation") as well as the assembly of prints into the outer membrane ("Export and Assembly of Outer Membrane Proteins in E. coli"). Although the emphasis of the book is on proteins, the role of phospholipids in controlling various cell surface processes is reviewed ("Role of Phospholipids in coli Cell Function"). I should point out the reason for the rapid progress in bacteria research is because of the possibility to apply biochemistry and genetics in this organism.

This book is a collection of carefully reviewed papers presented during the HP-SEE User Forum, the meeting of the High-Performance Computing Infrastructure for South East Europe s (HP-SEE) Research Communities, held in October 17-19, 2012, in Belgrade, Serbia. HP-SEE aims at supporting and integrating regional HPC infrastructures; implementing solutions for HPC in the region; and making HPC resources available to research communities in SEE, region, which are working in a number of scientific fields with specific needs for massively parallel execution on powerful computing resources. HP-SEE brings together research communities and HPC operators from 14 different countries and enables them to share HPC facilities, software, tools, data and research results, thus fostering collaboration and strengthening the regional and national human network; theproject specifically supports research groups in the areas of computational physics, computational chemistry and the life sciences. The contributions presented in this book are organized in four main sections: computational physics; computational chemistry; the life sciences; and scientific computing and HPC operations.

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This book presents authoritative recent research on Biomedical Informatics, bringing together contributions from some of the most respected researchers in this field. Biomedical Informatics represents a growing area of interest and innovation in the management of health-related data, and is essential to the development of focused computational models. Outlining the direction of current research, the book will be of considerable interest to theoreticians and application scientists alike. Further, as all chapters are self-contained, it also provides a valuable sourcebook for graduate students.

Interest in retinoic acid, the main biologically active derivative of vi- min A or retinol, increased dramatically between 1989 and 1993, following the cloning of nuclear receptors or RARs reported in 1987 (Fig. 1). Important discoveries since then have shown how RARs work as all-trans retinoic ac- dependent heterodimers with related nuclear receptors for 9-cis retinoic acid called RXRs. This has stimulated the development of synthetic analogs s- cific for each type of receptor, and opens the way to develop new methods for regulating pharmacologically the activity ofretinoic acid-dependent pathways of gene activation. The potential for the development of new drugs by the pharmaceutical industry is now a maj or factor driving forward our understa- ing of vitamin A-regulated pathways in animal development and homeostasis. However, apart from the real potential ofretinoid analogs as novel pharma- logical agents, there remains the considerable intellectual challenge of und- standing the way in which vitamin A and its derivatives function in cell development and differentiation. Retinoid Protocols is an attempt to bring together various methodologies that will be vital for rising to this challenge in the future. Retinoid molecular biology has few methods of its own, but is reliant on standard molecular biology methods applied to this particular research area.

Biotechnology is advancing at a rapid pace with numerous applications in medicine, industry, agriculture and environmental remediation. Recognizing this, government, industrial and academic research and development invest ment in biotechnology has expanded rapidly. The past decade has seen the emergence of applications of this technology with a dual-use potential. Mili tary applications focus on four major areas: biomedical technology, such as vaccine development and medical diagnostics; detection of toxins, chemicals and pathogens; material biotechnology; and biological decontamination, in cluding biodegradation and bioremediation. This conference emphasizes the non-medical applications of biotechnol ogy. The first two sessions focus on the synthesis and properties of molecules that may be used in detectors. The traditional approach to detection of chemical and biological agents relied on the development of specific assays or analyses for known agents. Advances in molecular biology have made possible the production of large quantities of toxins which were previously available in minute quantities, and the molecular engineering of toxins and pathogens with specific pharmacologic and physical-chemical properties. In addition to the traditional approaches to detection of specific known compounds, biotechnology now offers generic approaches to detection. Physiological targets, known as receptors, are primary targets for many drugs and toxins. Similarly, pathogens rely on receptors to gain access to cells. These receptors function as sensitive detectors, generating signals which are transduced and amplified."

Advances in Microbial Physiology, Volume 83 in this ongoing serial, highlights new advances in the field with this new volume presenting interesting chapters. Each chapter is written by an international board of authors. Topics of interest in this update include RidA paradigm, Targeting the cell envelope to overcome antimicrobial resistance, Biosynthesis and function of microbial methylmenaquinones, Antibiotic efficacy, Role of central metabolism/bacterial physiology on tolerance to cell wall-acting antibiotics, and Physiology of diazotrophs.

This volume introduces different concepts and methods of detecting RNA in biological material in a variety of model systems. The chapters in this book discuss methods that will answer numerous biological questions that arise in the study of RNAs. Some of the topics covered in this book are single mRNA molecule detection in embryos and neurons; detection of mRNA and associated molecules by ISH-IEM on frozen sections; optimizing molecular beacons for intracellular analysis of RNA; imaging translation dynamics of single mRNA molecules in live cells; preparation of high-throughput sequencing libraries; and capturing RNA binding proteins in embryos and in cell-culture. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, RNA Detection: Methods and Protocols is a valuable resource for novel and experiences scientist in the expanding field of RNAs.