The discovery of microRNAs and its role as gene expression regulators in human carcinogenesis represents one of the most important scientific achievements of the last decade. More recently, other non-coding RNAs have been discovered and its implications in cancer are emerging as well, suggesting a broader than anticipated involvement of the non-coding genome in cancer. Moreover, completely new and unexpected functions for microRNAs are being revealed, leading to the identification of new anticancer molecular targets. This book represents a comprehensive guide on non-coding RNAs and cancer, spanning from its role as cancer biomarkers, to providing the most useful bioinformatic tools, to presenting some of the most relevant discoveries, which indicates how these fascinating molecules act as fine orchestrators of cancer biology.

Systems Biology represents a new paradigm aiming at a whole-organism-level understanding of biological phenomena, emphasizing interconnections and functional interrelationships rather than component parts. The study of network properties, and how they control and regulate behavior from the cellular to organism level, constitutes a main focus of Systems Biology. This book addresses from a novel perspective a major unsolved biological problem: understanding how a cell works and what goes wrong in pathology. The task undertaken by the authors is in equal parts conceptual and methodological, integrative and analytical, experimental and theoretical, qualitative and quantitative, didactic and comprehensive. Essentially, they unravel the spatio-temporal unfolding of interacting mass-energy and information networks at the cellular and organ levels, as well as its modulation through activation or repression by signaling networks to produce a certain phenotype or (patho)physiological response.

Starting with the historical roots, in thirteen chapters this work explores the Systems Biology of signaling networks, cellular structures and fluxes, organ and microorganism functions. In doing so, it establishes the basis of a 21st century approach to biological complexity.

Defining and understanding cellular and molecular mechanisms that are relevant to women's health has become a critical area of scientific pursuit. Until recently, very little effort has been place on defining or understanding critical differences between women and men that may be critical to the overall health of the woman. In 1990, the National Institutes of Health recognized this gap in knowledge resulting in the creation of the Office of Research on Women's Health. One of the purposes of this office was to advance the understanding of health issues from the women's perspective from both a basic and clinical scientific perspective. From a scientific evolution of understanding, the existence of this office is new and thus there has not been enough time for new information to integrate itself in our current scientific thought process. This book will seek to capture and disseminate our current understanding of scientific advancements relevant to women's health and provide the information to a broad audience. The purpose of this work is to discuss recent advancements in basic science across three areas of concern for women's health. In addition, the book will provide "translational" chapters that attempt to place the basic science work in context within our current understanding of the human. Although it is well acknowledge that gender differences exist across organ function which translates into differences in whole body function, until recently little effort has been made to define basic mechanisms within various tissues within the woman. This work will focus on recent scientific findings that are relevant to women's health and to provide novel and relevant information to interested scientists and clinicians.

Within the past two decades, extraordinary new functions for the nucleolus have begun to appear, giving the field a new vitality and generating renewed excitement and interest. These new discoveries include both newly-discovered functions and aspects of its conventional role. The Nucleolus is divided into three parts: nucleolar structure and organization, the role of the nucleolus in ribosome biogenesis, and novel functions of the nucleolus.

Plant Proteomics: Methods and Protocols, Second Edition presents recent advances made in the field of proteomics and their application to plant biology and translational research. In recent years, improvements in techniques and protocols for high-throughput proteomics have been made at all workflow stages, from wet (sampling, tissue and cell fractionation, protein extraction, depletion, purification, separation, MS analysis, quantification) to dry lab (experimental design, algorithms for protein identification, bioinformatics tools for data analysis, databases, and repositories). Divided into nine convenient sections, chapters cover topics such as applications of gel-free, label- or label-free, imaging and targeted approaches to experimental model systems, crops and orphan species, as well as the study and analysis of PTMs, protein interactions, and specific families of proteins, and finally proteomics in translational research. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Plant Proteomics: Methods and Protocols, Second Edition seeks to serve both professionals and novices looking to exploit the full potential of proteomics in plant biology research.

The preceding volumes of Cell and Muscle Motility have focused on various aspects of motile systems in both muscle and non muscle cells. These essays have been critical reviews on topics of current interest and, hopefully, have provided a base from which future investigations may develop. During the past decade, however, much attention in the fields of biochemistry and cell biology has focused on motile systems in non muscle cells. Our current under- standing of the three-dimensional organization of the cytoplasm involve three major fibrous proteins which are collectively known as the cytoskeletal system. These polymorphic cytoskeletal proteins are microtubules (25-nm diameter), microfilaments (6-nm diameter), and intermediate filaments (lO-nm diame- ter). Microtubules consist of tubulin and several well-characterized micro- tubule associated proteins (MAPs) including MAP , MAP , tau, and others. l 2 Microfilaments consist of actin and associate with actin-binding proteins in- cluding a-actinin, filamin, myosin, tropomyosin, vinculin, and others. Inter- mediate filaments (lO-nm filaments) consist of at least five different tissue- specific classes, including desmin or skeletin (muscle), prekeratin (epithelial), vimentin (mesenchymal), neurofilament (nerve), and glial acidic fibrillary protein (astrocytes). These major fibrous proteins apparently interact with each other as well as other cytoplasmic components and appear to be inti- mately associated with such biological processes as cell shape changes, growth, motility, secretion, cell division, and uptake of materials from the exterior of the cell.

Colorectal cancer has for more than two decades served as the paradigm for the multi-step concept of cancer initiation and progression. Perhaps more than any other organ site, cancer of the colon is extensively characterized at the molecular level. We are now entering a time when molecular classification, rather than histologic classification, of cancer subtypes is driving the development of clinical trials with emerging targeted therapies. The book will focus on the progression from the identification of mutations that drive colorectal cancer initiation and progression to the search for novel therapies to treat the disease.

The Fifth Chinese Peptide Symposium, hosted by Lanzhou University, was held at Lanzhou, China July 14-17, 1998, with 156 participants, including 30 scientists from abroad, representing nine countries. The four-day conference was both intense and spiritually rewarding. Our goal for CPS-98 was to provide a forum for the exchange of knowledge, cooperation and friendship between the international and Chinese scientific communities, and we believe this goal was met. The symposium consisted of 8 sessions with 42 oral and 90 poster presentations, including synthetic methods, molecular diversity and peptide libraries, structure and conformation of peptides and proteins, bioactive peptides, peptide immunology, De Novo design and synthesis of proteins and peptides, ligand-receptor interactions, the chemistry-biology-interface and challenging problems in peptides. The enthusiastic cooperation and excellent contributions were gratifying and the active response of the invited speakers contributed to the success of the symposium. The presentations were of excellent caliber and represented the most current and significant aspects of peptide science. Dr. Kit Lam of the University of Arizona and Dr. Yun-Hua Ye of Peking University were the recipients of "The Cathay Award" sponsored by the H. H. Liu Education Foundation, offered for their seminal contribution in peptide science and the Chinese Peptide Symposium. Four outstanding young scientists were selected by the organizing committee to receive awards sponsored by Haikou Nanhai Pharmaceutical Industry Co. Ltd. (Zhong He Group).

The present book gives an overview on the similarities and differences of the various translation systems. Moreover, it highlights the mechanisms and control of translation in mitochondria and other organelles such as chloroplasts, plastids and apicoplasts in different organisms. Lastly, it offers an outlook on future developments and applications that might be made possible by a better understanding of translation in mitochondria and other organelles. "

In Protein Dynamics: Methods and Protocols, expert researchers in the field detail both experimental and computational methods to interrogate molecular level fluctuations. Chapters detail best-practice recipes covering both experimental and computational techniques, reflecting modern protein 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, Protein Dynamics: Methods and Protocols describes the most common and powerful methods used to characterize protein dynamics.

In Fluorescent Protein-Based Biosensors: Methods and Protocols, experts in the field have assembled a series of protocols describing several methods in which fluorescent protein-based reporters can be used to gain unique insights into the regulation of cellular signal transduction. Genetically encodable fluorescent biosensors have allowed researchers to observe biochemical processes within the endogenous cellular environment with unprecedented spatiotemporal resolution. As the number and diversity of available biosensors grows, it is increasingly important to equip researchers with an understanding of the key concepts underlying the design and application of genetically encodable fluorescent biosensors to live cell imaging. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Fluorescent Protein-Based Biosensors: Methods and Protocols promises to be a valuable resource for researchers interested in applying current biosensors to the study of biochemical processes in living cells as well as those interested in developing novel biosensors to visualize other cellular phenomena.

A key experiment in biomedical research is monitoring the expression of different proteins in order to detect changes that occur in biological systems under different experimental conditions. The method that is most widely used is the Western blot analysis. While Western blot is a workhorse in laboratories studying protein expression and has several advantages, it also has a number of significant limitations. In particular, the method is semi-quantitative with limited dynamic range. Western blot focuses on a single protein per sample with only a small number of representative samples analyzed in an experiment. New quantitative tools have been needed for some time to at least supplement, & possibly replace, the Western blot. Mass spectrometric methods have begun to compete with Western blot for routine quantitative analyses of proteins. One of these methods is based on the tandem mass spectrometry technique of selected reaction monitoring (SRM), which is also called multiple reaction monitoring (MRM). Selected reaction monitoring is actually an older tandem mass spectrometry technique, first described in the late 70s, that is widely utilized in the quantitative analysis of small molecules like drugs & metabolites. The use of selected reaction monitoring for the quantitative analysis of proteins has a number of advantages. Most importantly, it is fundamentally quantitative with a wide dynamic range. The output of the analysis is a numerical result that can range over several orders of magnitude. Other advantages include sufficient specificity & sensitivity to detect low abundance proteins in complex mixtures. Finally, selected reaction monitoring can be multiplexed to allow the quantitative analysis of relatively large numbers of proteins in a single sample in a single experiment. This Brief will explain both the theoretical & experimental details of the selected reaction monitoring experiment as it is applied to proteins.

This book offers comprehensive information on the polymorphisms of genes encoding pattern recognition receptors (PRRs). Following a short description of the general role of PRRs in the immune system, the structure and function of Toll-like and NOD-like receptors are examined in detail. The main focus is on the role of inherited variation in PRRs and their correlation to cancer and cardiovascular diseases. A review of all epidemiological investigations is included, and a concept of genomic risk markers for the prevention of various diseases is also discussed.

Featuring a diverse array of model organisms and scientific techniques, Sirtuins: Methods and Protocols collects detailed contributions from experts in the field addressing this vital family of genes. Opening with methods to generate sirtuin biology tools, the book continues by covering methods to identify sirtuin substrates, to measure sirtuin activity, and to study sirtuin biology. 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. Comprehensive and easy to use, Sirtuins: Methods and Protocols presents detailed protocols for sirtuin research that can be followed directly or modified to investigate new areas of sirtuin biology.

Christopher Schirwitz's thesis focuses on improving the quality of in situ synthesized high-complexity peptide micro arrays. Micro arrays containing proteins or small protein fragments in the form of peptides have become of great interest in proteomic research. With the help of these microarrays a large number of potential target molecules can be screened for interaction with a probe in a short timeframe. However, protein and peptide micro arrays are still lagging behind oligonucleotide arrays in terms of density, quality and manufacturing costs. A new approach developed at the German Cancer Research Center (DKFZ) has improved the synthesis of high-density peptide arrays. The current technology is capable of producing arrays with up to 40,000 different peptides per square cm by means of micro particle-based solid phase peptide synthesis. However, in situ synthesis approaches bear a conceptual disadvantage: The quality of the peptides is dependent on the efficiency of the synthesis so that peptide fragments are present in the resulting array among the desired full-length peptides. In peptide-protein interaction studies such peptide fragments. The central achievement of this thesis is the development of a new method allowing for the fast one-step purification of entire arrays without loss of resolution or spatial information. Christopher Schirwitz's work has resulted in a number of publications in high ranking journals.

Christopher M. Cheatum and Amnon Kohen, Relationship of Femtosecond-Picosecond Dynamics to Enzyme-Catalyzed H-Transfer. Cindy Schulenburg and Donald Hilvert, Protein Conformational Disorder and Enzyme Catalysis. A. Joshua Wand, Veronica R. Moorman and Kyle W. Harpole, A Surprising Role for Conformational Entropy in Protein Function. Travis P. Schrank, James O. Wrabl and Vincent J. Hilser, Conformational Heterogeneity Within the LID Domain Mediates Substrate Binding to Escherichia coli Adenylate Kinase: Function Follows Fluctuations. Buyong Ma and Ruth Nussinov, Structured Crowding and Its Effects on Enzyme Catalysis. Michael D. Daily, Haibo Yu, George N. Phillips Jr and Qiang Cui, Allosteric Activation Transitions in Enzymes and Biomolecular Motors: Insights from Atomistic and Coarse-Grained Simulations. Karunesh Arora and Charles L. Brooks III, Multiple Intermediates, Diverse Conformations, and Cooperative Conformational Changes Underlie the Catalytic Hydride Transfer Reaction of Dihydrofolate Reductase. Steven D. Schwartz, Protein Dynamics and the Enzymatic Reaction Coordinate.

Remarkably, while G protein-coupled receptors (GPCRs) are highly prevalent in animals and yeast, very few candidate GPCRs have been identified in plants. In G Protein-Coupled Receptor Signaling in Plants: Methods and Protocols, experts in the field describe techniques used in the study of small GTPases and related proteins. Beginning with a chapter on bioinformatics approaches for GPCR discovery, this detailed volume continues with chapters on heterotrimeric G protein subunits, Rab-GTPases, as well as lipid modifications, including myristoylation, acylation, and prenylation. 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. Practical and dependable, G Protein-Coupled Receptor Signaling in Plants: Methods and Protocols aims to aid further studies into the roles of small GTPases which will help elucidate numerous key processes in plants.

The lipid-rich and otherwise challenging nature of many key tissues complicates many aspects of current research, and applications of the unique nature of lipoproteins and their biological effects has engendered unique and vital methodologies. In Lipoproteins and Cardiovascular Disease: Methods and Protocols, experts in the field present a compendium of advanced and classical molecular biology methods targeted towards lipoprotein, atherosclerosis, and vascular biology research, bringing together in a single volume an updated set of protocols and strategies for methods now driving the most recent advances, along with classical methods that are still widely used. Among the many topics covered in this cutting-edge work, the book delves into crucial techniques such as quantitative real-time PCR, microarrays, RT-PCR laser capture microdissection, and tissue-specific gene overexpression, knockout, and knockdown methodologies, including AAV as a liver-directed gene delivery vehicle. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective subjects, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and valuable notes which highlight tips on troubleshooting and avoiding known pitfalls. Comprehensive and easy to use, Lipoproteins and Cardiovascular Disease: Methods and Protocols serves both novices and experts alike as a complete guide for any researcher with an interest in lipoproteins and their significant biological effects.

The dynamic field of flavin and flavoprotein biochemistry has seen rapid advancement in recent years. This comprehensive two volume set provides an overview of all aspects of contemporary research in this important class of enzymes. Topics treated include flavoproteins involved in energy generation, signal transduction and electron transfer (including respiration); oxygen activation by flavoproteins; the biology and biochemistry of complex flavoproteins; flavin and flavoprotein photochemistry/photophysics as well as biotechnological applications of flavoproteins. Recent developments in this field include new structures (including those of large membrane-integral electron transfer complexes containing FMN or FAD), elucidation of the role of flavoproteins in cell signalling pathways (including both phototaxis and the circadian cycle) and important new insights into the reaction mechanisms of flavin-containing enzymes. This volume focusing on complex flavoproteins and physical methods is an essential reference for all researchers in biochemistry, chemistry, photochemistry and photophysics working on flavoenzymes.

Excess of homocysteine, a product of the metabolism of the essential amino acid methionine, is associated with poor health, is linked to heart and brain diseases in general human populations, and accelerates mortality in heart disease patients. Neurological and cardiovascular abnormalities occur in patients with severe genetic hyperhomocysteinemia and lead to premature death due to vascular complications. Although it is considered a non-protein amino acid, studies over the past dozen years have discovered mechanisms by which homocysteine becomes a component of proteins. Homocysteine-containing proteins lose their normal biological function and become auto-immunogenic and pro-thrombotic. In this book, the author, a pioneer and a leading contributor to the field, describes up-to date studies of the biological chemistry of homocysteine-containing proteins, as well as pathological consequences and clinical implications of their formation. This is a comprehensive account of the broad range of basic science and medical implications of homocysteine-containing proteins for health and disease.

NMR Spectroscopy for Chemical Analysis at Low Magnetic Fields, by Stefan Gloggler, Bernhard Blumich, Stephan Appelt

Dynamic Nuclear Hyperpolarization in Liquids, by Ulrich L. Gunther

NMR with Multiple Receivers, by Eriks Kupce

TROSY NMR Spectroscopy of Large Soluble Proteins, by Yingqi Xu, Stephen Matthews

Solid-State NMR Spectroscopy of Proteins, by Henrik Muller, Manuel Etzkorn, Henrike Heise

Paramagnetic Solid-State Magic-Angle Spinning NMR Spectroscopy, by Guido Pintacuda, Gwendal Kervern"

Small proteins with molecular weights of <25 kDa are involved in major biological processes such as ribosome formation, stress adaption and cell cycle control. The study of the low-molecular-weight proteome has identified many central regulators of biology such as cytokines, chemokines, peptide hormones and proteolytic fragments of larger proteins. Due to the unique features of these proteins, the technical challenges are different from those in "common" proteomics. In The Low Molecular Weight Proteome: Methods and Protocols expert researchers from the field provide protocols for analysis of low molecular weight proteins and peptides, protocols for such methods applied in clinical research and an up-to-date review of quantitative protein profiling by labeling. These include methods suitable for both peptide and protein analysis with focus on methods and application that can be used for small protein analysis. 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, The Low Molecular Weight Proteome: Methods and Protocolsis a useful resource for experienced proteomics practitioners as well as an aid to newcomers who wish to become acquainted with the theory and practice of a wide array of methods in analyzing small proteins or peptides.

Proteins are the cell's workers, their messengers and overseers. In these roles, proteins specifically bind small molecules, nucleic acid and other protein partners. Cellular systems are closely regulated and biologically significant changes in populations of particular protein complexes correspond to very small variations of their thermodynamics or kinetics of reaction. Interfering with the interactions of proteins is the dominant strategy in the development of new pharmaceuticals. Protein Ligand Interactions: Methods and Applications, Second Edition provides a complete introduction to common and emerging procedures for characterizing the interactions of individual proteins. From the initial discovery of natural substrates or potential drug leads, to the detailed quantitative understanding of the mechanism of interaction, all stages of the research process are covered with a focus on those techniques that are, or are anticipated to become, widely accessible and performable with mainstream commercial instrumentation. Written in the highly successful Methods in Molecular Biology 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, Protein Ligand Interactions: Methods and Applications, Second Edition serves as an ideal guide for researchers new to the field of biophysical characterization of protein interactions - whether they are beginning graduate students or experts in allied areas of molecular cell biology, microbiology, pharmacology, medicinal chemistry or structural biology.

Regulated turnover of extracellular matrix (ECM) is an important component of tissue homeostasis. In recent years, the enzymes that participate in, and control ECM turnover have been the focus of research that touches on development, tissue remodeling, inflammation and disease. This volume in the "Biology of Extracellular Matrix" series provides a review of the known classes of proteases that degrade ECM both outside and inside the cell. The specific EMC proteases that are discussed include cathepsins, bacterial collagenases, matrix metalloproteinases, meprins, serine proteases, and elastases. The volume also discusses the domains responsible for specific biochemical characteristics of the proteases and the physical interactions that occur when the protease interacts with substrate. The topics covered in this volume provide an important context for understanding the role that matrix-degrading proteases play in normal tissue remodeling and in diseases such as cancer and lung disease.

The essential question that fractal dimensions attempt to answer is about the scales in Nature. For a system as non-idealistic and complex as a protein, studying scale-invariance becomes particularly important.

"Fractal Symmetry of Protein Interior" investigates the diverse facets of the various scales at which we describe protein biophysical and biochemical phenomena. Following a thorough introduction to fractal dimensions, fractal-dimension-based approaches, that have been employed to study protein interior biophysical properties, are described. The focus is on the question which scales are scale-invariant? Investigations related to scaling of biophysical and biochemical behaviors may one day help us to formulate a fundamental theory about protein biophysics; which, in turn, may help us to understand fundamental principles of proteins."