This book is the latest volume in the highly successful series Comprehensive Biochemistry. It provides a historical and autobiographical perspective of the developments in the field through the contributions of leading individuals who reflect on their careers and their impact on biochemistry. Volume 44 is essential reading for everyone from graduate student to professor, placing in context major advances not only in biochemical terms but in relation to historical and social developments. Readers will be delighted by the lively style and the insight into the lives and careers of leading scientists of their time.
* Contributors are distinguished scientists in the field
* Unique series of personal recollections
* Presents scientific research in a historical perspective

This book focuses on the application of fluorescence to study motor proteins (myosins, kinesins, DNA helicases and RNA polymerases). It is intended for a large community of biochemists, biophysicists and cell biologists who study a diverse collection of motor proteins. It can be used by researchers to gain an insight into their first experiments, or by experienced researchers who are looking to expand their research to new areas. Each chapter provides valuable advice for executing the experiments, along with detailed background knowledge in order to develop own experiments.

Driving further the research on mammalian alkaline phosphatase structure and function, Phosphatase Modulators collects expert contributions into one "how to" manual for basic scientists interested in initiating a drug discovery effort. While this book contains the traditional method chapters and some typical reviews on the structure and known functions of phosphatases, other contributions are meant to discuss approaches and alternatives useful in making "go/no-go" decisions in high throughput screening (HTS) and lead optimization campaigns. Many chapters focus on tissue-nonspecific alkaline phosphatase (TNAP) as well as protein phosphatases. Written for the highly successful Methods in Molecular Biology series, chapters in this volume include the kind of detail and key implementation advice that promotes reproducible results. Step-by-step and practical, Phosphatase Modulators offers a path to understanding many of the facets and complexities associated with undertaking a drug discovery effort and will serve as a roadmap to initiating those efforts.

Phosphorus (P) is a finite resource which is essential for life. It is a limiting nutrient in many ecosystems but also a pollutant which can affect biodiversity in terrestrial ecosystems and change the ecology of water bodies. This book collects the latest information on biological processes in soil P cycling, which to date have remained much less understood than physico-chemical processes. The methods section presents spectroscopic techniques and the characterization of microbial P forms, as well as the use of tracers, molecular approaches and modeling of soil-plant systems. The section on processes deals with mycorrhizal symbioses, microbial P solubilization, soil macrofauna, phosphatase enzymes and rhizosphere processes. On the system level, P cycling is examined for grasslands, arctic and alpine soils, forest plantations, tropical forests, and dryland regions. Further, P management with respect to animal production and cropping, and the interactions between global change and P cycling, are treated.

Experts from around the world review the current field of the immunobiology of heat shock proteins, and provide a comprehensive account of how these molecules are spearheading efforts in the understanding of various pathways of the immune system. This one-stop resource contains numerous images to both help illustrate the research on heat shock proteins, and better clarify the field for the non-expert. Heat shock proteins (HSPs) were discovered in 1962 and were quickly recognized for their role in protecting cells from stress. Twenty years later, the immunogenicity of a select few HSPs was described, and for the past 30 years, these findings have been applied to numerous branches of immunology, including tumor immunology and immunosurveillance, immunotherapy, etiology of autoimmunity, immunotherapy of infectious diseases, and expression of innate receptors. While HSPs can be used to manipulate immune responses by exogenous administration, they appear to be involved in initiation of de novo immune responses to cancer and likely in the maintenance of immune homeostasis.

Poly (ADP-ribose) Polymerases (PARPs) are abundant and ubiquitous proteins that regulate crucial processes of the cell cycle, DNA repair, genomic stability, and transcriptional regulation. Being involved in basic cell functions, PARPs mediate rapid responses to such environmental factors as stress, infection, nutrition and hormonal signals. Whereas PARP inhibitors can suppress tumor growth and proliferation in certain breast, ovarian, and prostate cancers, understanding how PARP controls cellular functions is essential for the development of novel cancer treatments strategies. Divided into three convenient sections, Poly(ADP-Ribose) Polymerase: Methods and Protocols aims to explain how PARP proteins act within the normal development of an organism as well as in pathogenic conditions, seeks to advance the knowledge of developmental pathways regulation, and endeavors to facilitate the development of new therapeutic drugs and methods to target PARP-dependent processes. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Poly(ADP-Ribose) Polymerase: Methods and Protocols serves as an ideal guide to scientists who wish to continue exploring this exciting and progressive research field.

This book aims to bridge the gap in understanding how protein-tyrosine phosphatases (PTPs), which carry out the reverse reaction of tyrosine phosphorylation, feature in cancer cell biology. The expertly authored chapters will first review the general features of the PTP superfamily, including their overall structure and enzymological properties; use selected examples of individual PTP superfamily members, to illustrate emerging data on the role of PTPs in cancer; and will review the current status of PTP-based drug development efforts. Protein Tyrosine Phosphatases in Cancer,from renowned researchers Benjamin Neel and Nicholas Tonks, is invaluable reading for researchers in oncology, stem cell signaling,and biochemistry.

This volume aims to provide protocols on a wide range of biochemical methods, analytical approaches, and bioinformatics tools developed to analyze the proteome. 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, Proteomics: Methods and Protocols aims to ensure successful results in the further study of this vital field.

Genetics of Prion Disease, by S. Lloyd, S. Mead and J. Collinge. Atypical Prion Diseases in Humans and Animals, by M. A. Tranulis, S. L. Benestad, T. Baron and H. Kretzschmar. Chronic Wasting Disease, by S. Gilch, N. Chitoor, Y. Taguchi, M. Stuart, J. E. Jewell and H. M. Schatzl. Transgenic Mouse Models and Prion Strains, by G. C. Telling. Neuroprotective and Neurotoxic Signaling by the Prion Protein, by U. K. Resenberger, K. F. Winklhofer and J. Tatzelt. Prion Seeded Conversion and Amplification Assays, by C. D. Orru and B. Caughey. Prion Protein and Its Conformational Conversion: A Structural Perspective, by W. K. Surewicz and M. I. Apostol. Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations, by M.W. van der Kamp and V. Daggett. Chemical Biology of Prion Protein: Tools to Bridge the In Vitro/Vivo Interface, by R. Seidel and M. Engelhard. The PrP-Like Proteins Shadoo and Doppel, by D. Westaway, N. Daude, S. Wohlgemuth and P. Harrison. Fungal Prions: Structure, Function and Propagation, by M. F. Tuite, R. Marchante and V. Kushnirov."

Intermediate filaments are a large family of proteins that are the cytoskeletal elements involved in a number of skin, liver, neuromuscular, cardiac, eye and hair diseases. Intermediate filament genes are regulated in a tissue-and cell type-specific manner and their polymerized protein products protects the cells and tissue they are part of against a variety of mechanical and nonmechanical stresses. This book provides a comprehensive resource of methodology essentials, describing a variety of essential tools and assays for studying intermediate filaments. The book provides user-friendly advice and protocols covering all aspects of intermediate filaments including protein isolation and structure, protein and gene regulation, relationship to disease and apoptosis, and associated proteins. Both mammalian and non-mammalian systems and animal models are covered, making this book a must-have for any investigator wishing to study IF genes or their protein products.
* Covers intermediate filaments from crystallography, protein chemistry, cell and molecular biology, microrheology, gene regulation, to animal models and human disease
* Practical and user-friendly with detailed "how-to-protocols and "tricks of the trade"
* Includes detailed tables of useful reagents, vendors and web links

Real-time PCR (RT-PCR) technology is highly flexible and many alternative instruments and fluorescent probe systems have been developed recently. The decreased hands-on time, increased reliability, and improved quantitative accuracy of RT-PCR methods have contributed to the adoption of RT-PCR for a wide range of new applications. This essential manual presents a comprehensive guide to the most up-to-date technologies and applications, as well as providing an overview of the theory of this increasingly important technique. Renowned experts in the field describe and discuss the latest PCR platforms, fluorescent chemistries, validation software, data analysis, and internal and external controls. This timely and authoritative volume also discusses a wide range of RT-PCR applications including clinical diagnostics, biodefense, RNA expression studies, validation of array data, mutation detection, food authenticity and legislation, NASBA, molecular halotyping, and much more. Real-Time PCR: Current Technology and Applications will be an essential book for all laboratories using PCR.

This detailed book provides technical approaches to tackle a variety of questions related to intracellular lipid transport in order to improve our understanding at different scales of how lipids are accurately displaced between organelles, across long distances or at membrane contact sites, or within cellular membranes. The volume begins with methodologies to measure the movement of varied lipid species between or in organelle membranes, inside eukaryotic cells, including plant cells, or in bacteria, and continues in vitro or in silico approaches aiming to define, more from a biochemical and structural standpoints, how lipid transfer proteins (LTPs) or flippases/scramblases precisely function. 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 laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Intracellular Lipid Transport: Methods and Protocols serves as an ideal guide for researchers seeking to shed light on diverse aspects of this critical and often elusive cellular process.

This sixth volume in this established series deals with the biochemical responses of fish to different environmental/ecological factors. Environmental Toxicology captures vital issues affecting the responses of fish to the chemical surroundings of their environment. Chapters included in this volume identify the systems found in fish to deal with xenobiotics, hormonal interactions initiated in the presence of these chemicals, the unique mechanisms used by fish to adjust to the present chemicals, and the new and evolving mixtures of chemicals in their environment. Also included, is a crucial review of the new methods being applied in fish systems to understand the effects of xenobiotics to fish fitness - a key theme in environmental health and critical to the future of fish populations.
* Entirely new topic discussion and most recent volume in the acclaimed series
* Includes chapters detailed on a cellular level
* Introduces discussion of pharmaceutical effects on fish

Michael D. Wendt
Protein-Protein Interactions as Drug Targets

Shaomeng Wang, Yujun Zhao, Denzil Bernard, Angelo Aguilar, Sanjeev Kumar
Targeting the MDM2-p53 Protein-Protein Interaction for New Cancer Therapeutics

Kurt Deshayes, Jeremy Murray, Domagoj Vucic
The Development of Small-Molecule IAP Antagonists for the Treatment of Cancer

John F. Kadow, David R. Langley, Nicholas A. Meanwell, Michael A. Walker, Kap-Sun Yeung, Richard Pracitto
Protein-Protein Interaction Targets to Inhibit HIV-1 Infection
Nicholas A. Meanwell, David R. Langley
Inhibitors of Protein-Protein Interactions in Paramyxovirus Fusion a Focus on Respiratory Syncytial Virus

Andrew B. Mahon, Stephen E. Miller, Stephen T. Joy, Paramjit S. Arora
Rational Design Strategies for Developing Synthetic Inhibitors of Helical Protein Interfaces

Michael D. Wendt
The Discovery of Navitoclax, a Bcl-2 Family Inhibitor

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A direct spinoff of the Advances in Enzyme Regulation journal this internationally acclaimed series reports progress at the cutting edge in the strategic area of regulation at the molecular level. In an integrated presentation of original papers, leading scientists, Nobel Prize winners and other outstanding experts from many countries review the best research produced each year and evaluate what is newest and what promises to be the most important in clinical and basic investigations.
The volumes serve as guideposts and beacons for investigators in planning research and teaching students in basic and clinical fields of endeavour. These books advance the general front of studies on metabolic regulation and the understanding of the molecular biology of control of gene expression by hormones, drugs and growth factors in cancer cells and in clinical situations of diabetes, inborn errors of metabolism and neoplasia.

High quality leads provide the foundation for the discovery of successful clinical development candidates, and therefore the identi?cation of leads is an essential part of drug discovery. The process for the identi?cation of leads generally starts with the screening of a compound collection, either an HTS of a relatively large compound collection (hundreds of thousands to one million plus compounds) or a more focused screen of a smaller set of compounds that have been preselected for the target of interest. Virtual screening methods such as structure-based or pharmacophore-based searches can complement or replace one of the above approaches. Once hits are identi?ed from one or more of these screening methods, they need to be thoroughly characterized in order to con?rm activity and identify areas in need of optimization. Finally, once fully characterized hits are identi?ed, preliminary optimization through synthetic modi?cation is carried out to generate leads. Parallel optimization of all properties, including biological, physicochemical, and ADME is the most ef?cient approach to the identi?cation of leads. Hit characterization is described in the previous chapter. The focus of this chapter is on hit optimization and the identi?- tion of leads. After a general overview of these processes, examples taken from the literature since 2001 will be used to illustrate speci?c points. There are also a number of excellent reviews covering the lead identi?cation process [1-6].

Receptor Tyrosine Kinase: Structure, Functions and Role in Human Disease, for the first time, systematically covers the shared structural and functional features of the RTK family. Receptor Tyrosine Kinases (RTKs) play critical roles in embryogenesis, normal physiology and several diseases. And over the last decade they have become the Number 1 targets of cancer drugs. To be able to conduct fundamental research or to attempt to develop pharmacological agents able to enhance or intercept them, it is essential first to understand the evolutionary origin of the 58 RTKs and their roles in invertebrates and in humans, as well as downstream signaling pathways. The assembly of chapters is written by experts and underscores commonalities between and among the RTKs. It is an ideal companion volume to The Receptor Tyrosine Kinase: Families and Subfamilies, which proceeds, family by family through all of the specific subfamilies of RTKs, along with their unique landmarks.

This volume of Modern Aspects of Electrochemistry reviews the latest developments in electrochemical science and technology related to biomedical and pharmaceutical applications. In particular, this book discusses electrochemical applications to medical devices, implants, antimicrobially active materials, and drug delivery systems.

Liposomes are cellular structures made up of lipid molecules. Important as a cellular model in the study of basic biology, liposomes are also used in clinical applications such as drug delivery and virus studies. Liposomes Part D is a continuation of previous MIE Liposome volumes A, B, and C.
Contents: Antibody or Ligand Targeted Liposomes; environment sensitive liposomes; liposomal oligonucleotides; liposomes in vivo

Thermodynamics was created in the ?rst half of the 19th century as a theory designed to explain the functioning of heat engines converting heat into mechanical work. In the course of time, while the scope of research in this ?eld was being extended to a wider and wider class of energy transformations, thermodynamics came to be considered as a general theory of machines identi?ed with energy transducers. Imp- tant progress in biochemistry in the ?rst half of the 20th century, and in molecular biology in the second half, made it possible to think of treating even living organisms as machines, at least on the subcellular level. However, success in applying thermodynamics to elucidate the phenomenon of life has been rather mitigated. Two reasons seem to be responsible for this unsatisfactory s- uation. Nineteenth century thermodynamics dealt only with simple (homogeneous) systems in complete equilibrium. Although during the 20th century a nonequilibrium thermodynamics was developed, sta- ing with the Onsager theory of linear response and ending with the Prigogine nonlinear theory of dissipative structures, these theories still concern the originally homogeneous systems. Because living organisms are complex systems with a historically frozen spatial and functional structure, a thermodynamics of both nonequilibrium and complex s- tems is needed for their description. The ?rst goal of the present book is to formulate the foundations of such a thermodynamics.

This book presents modern and classic analytical approaches that are crucial for the biochemical and functional characterization of the archetypal protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The distinguishing feature of the book is that it covers, in addition to other methods, some of the uncommon but valuable techniques as well. For example, in-gel visualization of enzyme activity, immunoblotting protocols for native (non-denatured) proteins, and proteins resolved by pH-gradient [IEF-isoelectrofocusing], etc. These expedient methods are relevant and vital for the verification of biochemical properties of GAPDH, or similar protein of interest. This work outlines detailed protocols that are essential to investigate classical (cellular) and recently reported extracellular (secretory) isoforms of GAPDH. Precisely, the book covers techniques pertinent to enzymatic and non-enzymatic analysis of GAPDH that include, but not limited to, electrophoretic mobility shift assay (EMSA), two-dimensional (2D)-immunoblotting, immunofluorescence/confocal microscopy, mass spectrometry, ion-exchange and affinity chromatography. Readers will discover the importance of the experimental methods described in the book as they relate to the evaluation of the role and significance of GAPDH. Furthermore, majority of the methods described in the book have also been validated in the author's laboratory, besides other research groups worldwide, underlining the repeatability and reproducibility of the protocols. Each method begins with an abstract and a brief background emphasizing its application and relevance. This will enable the readers to determine the choice of experimental design according to their research objectives. The book explains the methods systematically with ample illustrations to facilitate quick and easy comprehension of the practical knowledge. Although the book is focused on GAPDH, many of the protocols may be adopted to other proteins or enzymes with minimal modifications. Noteworthy, it is unequivocally established that GAPDH is a multifunctional protein involved in several cellular processes of health & disease conditions. Hence, this book will be a valuable practical guide for young researchers, scientists and clinician-scientists.

This volume continues the in-depth treatment of the topic and covers the RSG protein superfamily including RZ, R4, R7, R12, RhoGEF, and GRK, as well as other heterotrimeric G-protein signaling regulators.
Table of Contents
-RZ Subfamily
-R4 Subfamily
-R7 Subfamily
-R12 Subfamily
-RhoGEF Subfamily
-GRK Subfamily
-Other RGS proteins
-Activators
-Inhibitors
-Other Modulators

This first volume of the Trilogy of Traditional Foods, part of the ISEKI Food Series, covers general and consumer aspects of traditional foods. It offers numerous recipes of traditional foods from across the world, with some chapters providing detailed descriptions on how to mix, cook, bake or store a particular food item in order to produce the desired effect. Traditional Foods; General and Consumer Aspects is divided into six sections. The first section focuses on general aspects of traditional foods and covers the perception of traditional foods and some general descriptions of traditional foods in different countries. This is followed by sections on Traditional Dairy Products, Traditional Cereal Based Products, Traditional Meat and Fish Products, Traditional Beverages and Traditional Deserts, Side Dishes and Oil products from various countries. The international List of Contributors, which includes authors from China, Bulgaria, Portugal, France, Norway, Romania, Slovakia, and Brazil, to name a few, shows its truly international perspective. The volume caters to the practicing food professional as well as the interested reader.

Respiration in plants, as in all living organisms, is essential to provide metabolic energy and carbon skeletons for growth and maintenance. As such, respiration is an essential component of a planta (TM)s carbon budget. Depending on species and environmental conditions, it consumes 25-75% of all the carbohydrates produced in photosynthesis a" even more at extremely slow growth rates. Respiration in plants can also proceed in a manner that produces neither metabolic energy nor carbon skeletons, but heat. This type of respiration involves the cyanide-resistant, alternative oxidase; it is unique to plants, and resides in the mitochondria. The activity of this alternative pathway can be measured based on a difference in fractionation of oxygen isotopes between the cytochrome and the alternative oxidase. Heat production is important in some flowers to attract pollinators; however, the alternative oxidase also plays a major role in leaves and roots of most plants. A common thread throughout this volume is to link respiration, including alternative oxidase activity, to plant functioning in different environments.