The Fifteen American Peptide Symposium (15APS) was held in Nashville, Tennessee, on June 14-19, 1997. This biennial meeting was jointly sponsored by the American Peptide Society and Vanderbilt University. The attendance of 1,081 participants from 37 countries was lower than the two previously held Symposia. However, the number of participating countries was the largest. Thus, it was gratifying to see that this meeting retained both its international flavor and participant loyalty at a time when there are many more symposia held each year on similar subjects. The scientific program, thanks to the insights and efforts of the Program Committee as well as Dr. Peter Schiller, the President of the American Peptide Society, was extraordinarily rich, diverse, and exciting. It was comprised of 124 oral and 550 poster presentations. Three prominent format changes were installed. First, the Symposium started on Saturday instead of Sunday. Second, the program opened on Saturday afternoon with a Mini-symposium by the Young Investigators to give them an early start and attention. Finally, 40 short and definitive reports were given in two parallel sessions. The expanded format permitted an unprecedented number of lectures and enabled wider participation by the attending delegates.

In the late 1980s, Peptide Societies were established in Europe, the United States, and Japan, and more recently, in the Asian and the Pacific Rim regions including Australia, China, and Korea. At the time of the establishment of the American, European and Japanese Peptide Societies, the International Liaison Organizing Committee representing these Peptide Societies, along with the Australian Peptide Society, began discussions for holding international confer ences which would supercede or be held in lieu of the numerous individual meetings, held by the peptide societies of each individual country or region. The representative of the Chinese Peptide Society participated in these discus sion in the International Liaison Organizing Committee at the meeting of the American Peptide Symposium in Nashville, in June 1997. After lengthy discus sions over several years, we agreed to organize and host the International Peptide Symposium in Japan. The First International Peptide Symposium (IPS'97) was held on November 30-December 5, 1997, in Kyoto, and was co sponsored by four Peptide Societies. The attendance at this Symposium was 550 participants, including representatives from 32 different countries. We were very pleased with this outcome and anticipate an even larger attendance for forthcoming Symposia in future years. The revolution and advances in science and technology during the past two decades has caused traditional peptide chemistry to expand to peptide science, spreading from physical science to biology, pharmacology, and medicine.

This book summarizes present knowledge of different mechanisms involved in the development of positive and negative consequences of cardiac adaptation. Particular attention is paid to the still underestimated adaptive cardiac responses during development, to adaptation to the frequently occurring pressure and volume overload as well as to cardiac changes, induced by enduring exercise and chronic hypoxia. Cardiac Adaptations will be of great value to cardiovascular investigators, who will find this book highly useful in their cardiovascular studies for finding solutions in diverse pathological conditions; it will also appeal to students, fellows, scientists, and clinicians interested in cardiovascular abnormalities.

Since its ?rst description in 1942 in both serum and cerebrospinal ?uid, transthyretin (TTR) has had an eventful history, including changes in name from "prealbumin" to "thyroxine-binding prealbumin" to "transthyretin" as knowledge increased about its functions. TTR is synthesised in a wide range of tissues in humans and other eutherian mammals: the liver, choroid plexus (blood- cerebrospinal ?uid barrier), retinal pigment epithelium of the eye, pancreas, intestine and meninges. However, its sites of synthesis are more restricted in other vertebrates. This implies that the number of tissues synthesising TTR during vertebrate evolution has increased, and raises questions about the selection pressures governing TTR synthesis. TTR is most widely known as a distributor of thyroid hormones. In addition, TTR binds retinol-binding protein, which binds retinol. In this way, TTR is also involved with retinoid distribution. More recently, TTR has been demonstrated to bind a wide variety of endocrine disruptors including drugs, pollutants, industrial compounds, heavy metals, and some naturally occurring plant ?avonoids. These not only interfere with thyroid hormone delivery in the body, but also transport such endocrine disruptors into the brain, where they have the potential to accumulate.

This book provides a premier resource on understanding the ribosome's essential nature and how it interacts with other proteins and nucleic acids to control protein synthesis. As one of the central foundations in our understanding of the biology at the molecular level, this topic appeals to a wide audience, from bench researcher to clinician. With the advent of atomic scale structures, methods to visualize and separate individual molecules, and the computational power to model the complex interactions of over a million atoms at once, our understanding of how gene expression is controlled at the level of protein translation is now deeply ensconced in the biophysical realm.

Gene function annotation has been a central question in molecular biology. The importance of computational function prediction is increasing because more and more large scale biological data, including genome sequences, protein structures, protein-protein interaction data, microarray expression data, and mass spectrometry data, are awaiting biological interpretation. Traditionally when a genome is sequenced, function annotation of genes is done by homology search methods, such as BLAST or FASTA. However, since these methods are developed before the genomics era, conventional use of them is not necessarily most suitable for analyzing a large scale data. Therefore we observe emerging development of computational gene function prediction methods, which are targeted to analyze large scale data, and also those which use such omics data as additional source of function prediction. In this book, we overview this emerging exciting field. The authors have been selected from 1) those who develop novel purely computational methods 2) those who develop function prediction methods which use omics data 3) those who maintain and update data base of function annotation of particular model organisms (E. coli), which are frequently referred

The phrase "Life, stress and death" connects three terms, but is there a biological basis for that? Are there molecules that are essential to/or mediate these phenomena? This contributory volume "Mortalin Biology: Life, Stress and Death" is a remarkable compilation of the research outcomes on the stress protein mortalin, a member of heat shock 70 family of proteins. The book is unique as it describes mortalin playing essential role in life, stress response and death either from cancer, when it becomes hyperactive or from neuro-degeneration, when it becomes hypoactive. The book provides up-to-date knowledge on mortalin with respect to its discovery, structure, evolutionary conservation, function and signal transduction in different organisms in a simple, but most comprehensive way, that besides offering an enjoyable and in-depth reading, prompts the reader to ask further questions to explore this protein with new ideas, approaches and experiments. Twenty-one chapters by the world leaders on the specific areas of mortalin research throw light on its multi-functionality, potentials for biotechnology, diagnostics and therapeutic values. Avenues of mortalin biology, yet unexplored, hold immense promises for future, and reading this volume provides an easy, enthusiastic and energetic head-on start.

If theoretical physicists can seriously entertain canonical "standard models" even for the big-bang generation of the entire universe, why cannot life scientists reach a consensus on how life has emerged and settled on this planet? Scientists are hindered by conceptual gaps between bottom-up inferences (from early Earth geological conditions) and top-down extrapolations (from modern life forms to common ancestral states). This book challenges several widely held assumptions and argues for alternative approaches instead. Primal syntheses (literally or figuratively speaking) are called for in at least five major areas. (1) The first RNA-like molecules may have been selected by solar light as being exceptionally photostable. (2) Photosynthetically active minerals and reduced phosphorus compounds could have efficiently coupled the persistent natural energy flows to the primordial metabolism. (3) Stochastic, uncoded peptides may have kick-started an ever-tightening co-evolution of proteins and nucleic acids. (4) The living fossils from the primeval RNA World thrive within modern cells. (5) From the inherently complex protocellular associations preceding the consolidation of integral genomes, eukaryotic cell organization may have evolved more naturally than simple prokaryote-like life forms. - If this book can motivate dedicated researchers to further explore the alternative mechanisms presented, it will have served its purpose well.

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.

This book offers a balanced mixture of practice-oriented information and theoretical background as well as numerous references, clear illustrations, and useful data tables. Problems and solutions are accessible via a special website. This new edition has been completely revised and extended; it now includes three new chapters on tandem mass spectrometry, interfaces for sampling at atmospheric pressure, and inorganic mass spectrometry.

Legumes have high potential for improving the nutritional quality of foods, but limited data on their bioactive compounds exists. Results of clinical and epidemiological studies suggest that natural antioxidants can protect us against oxidative stress that is closely associated with cancer and cardiovascular disease. Legumes are a valuable source of bioactive compounds such as phenolic compounds, peptides and non-nutritional factors. They are rich in several important micronutrients, including potassium, magnesium, folate, iron, and zinc, and are an important source of protein in vegetarian diets. They are among the only plant foods that provide significant amounts of the amino acid, lysine. Commonly consumed legumes are also rich in total and soluble fibre as well as in resistant starch. This book provides a comprehensive overview of the antioxidant activity and health aspects of legumes. The international spread of contributors will describe the key factors that influence consumer acceptance of legumes in the diet, as well as the known functional properties of legumes and legume based food products. It will serve as an excellent and up-to-date reference for food scientists, food chemists, researchers in human nutrition, dietetics and the chemistry of natural compounds.

In this thesis, the author investigates the chemistry and application of molecules containing urea and amide bonds. These bonds are some of the strongest known and are fundamental to biological processes. The author describes his discovery that sterically hindered ureas undergo solvolysis at room temperature under neutral conditions. This is a remarkable finding, since ureas are inert under these conditions and a general rule of chemistry is that hindered substrates are less reactive. Remarkably, the author translates these results to the correspondingly sterically hindered amides. This thesis has resulted in a number of outstanding publications in high profile journals. The unique method for breaking urea and amide bonds developed in this study is likely to have far reaching consequences for biological protein manipulation.

TwentyyearshavegonebysinceJackSokatch?rstpublishedhisoutsta- ingTheBiologyofPseudomonasbackin1986.Thiswasfollowedbytwobooks published by the ASM that contained the presentations of the Pseudomonas meetings held in Chicago in 1989 and Trieste in 1991. The earlier volume of these two was edited by Simon Silver, Al Chakrabarty, Barbara Iglewski, and Sam Kaplan, and the later one by Enrica Galli, Simon Silver, and Bernard Witholt. The time was ripe for a series of books on Pseudomonas because of its importance in human and plant pathogenesis, bio?lms, soil and rhizosphere colonization, etc. Efforts were devoted to produce the ?rst three volumes of the series on the biology of Pseudomonas after a meeting with Kluwer staff members in August 2002 during the XI IUMS conference in Paris (France). In less than a year a group of outstanding scientists in the ?eld, after devoting much of their valuable time, managed to complete their chapters for the three volumes of the series. To ensure the high standard of each chapter, renowned scientists participated in the reviewing process. The three books collected part of the "explosion" of new vital information on the genus Pseudomonas.

Knowledge of the extracellular matrix (ECM) is essential to understand cellular differentiation, tissue development, and tissue remodeling. This volume of the series "Biology of Extracellular Matrix" provides a timely overview of the structure, regulation, and function of the major macromolecules that make up the extracellular matrix. It covers topics such as collagen types and assembly of collagen-containing suprastructures, basement membrane, fibronectin and other cell-adhesive glycoproteins, proteoglycans, microfibrils, elastin, fibulins and matricellular proteins, such as thrombospondin. It also explores the concept that ECM components together with their cell surface receptors can be viewed as intricate nano-devices that allow cells to physically organize their 3-D-environment. Further, the role of the ECM in human disease and pathogenesis is discussed as well as the use of model organisms in elucidating ECM function.

Recent developments in computer science enable algorithms previously perceived as too time-consuming to now be efficiently used for applications in bioinformatics and life sciences. This work focuses on proteins and their structures, protein structure similarity searching at main representation levels and various techniques that can be used to accelerate similarity searches. Divided into four parts, the first part provides a formal model of 3D protein structures for functional genomics, comparative bioinformatics and molecular modeling. The second part focuses on the use of multithreading for efficient approximate searching on protein secondary structures. The third and fourth parts concentrate on finding 3D protein structure similarities with the support of GPUs and cloud computing. Parts three and four both describe the acceleration of different methods. The text will be of interest to researchers and software developers working in the field of structural bioinformatics and biomedical databases.

Amyloid-forming proteins are implicated in over 30 human diseases. The proteins involved in each disease have unrelated sequences and dissimilar native structures, but they all undergo conformational alterations to form fibrillar polymers. The fibrillar assemblies accumulate progressively into disease-specific lesions in vivo. Substantial evidence suggests these lesions are the end state of aberrant protein folding whereas the actual disease-causing culprits likely are soluble, non-fibrillar assemblies preceding the aggregates. The non-fibrillar protein assemblies range from small, low-order oligomers to spherical, annular, and protofibrillar species. Oligomeric species are believed to mediate various pathogenic mechanisms that lead to cellular dysfunction, cytotoxicity, and cell loss, eventuating in disease-specific degeneration and systemic morbidity. The particular pathologies thus are determined by the afflicted cell types, organs, systems, and the proteins involved. Evidence suggests that the oligomeric species may share structural features and possibly common mechanisms of action. In many cases, the structure function interrelationships amongst the various protein assemblies described in vitro are still elusive. Deciphering these intricate structure function correlations will help understanding a complex array of pathogenic mechanisms, some of which may be common across different diseases albeit affecting different cell types and systems."

The motivation for us to conceive this series of volumes on regulation was mainly our belief that it would be fun, and at the same time productive, to approach the subject in a way that differs from that of other treatises. We thought it might be interesting and instructive for both author and reader-to examine a particular area of investigation in a framework of many different problems. Cutting across the traditional boundaries that have separated the subjects in past volumes on regulation is not an easy thing to do-not because it is difficult to think of what interesting topics should replace the old ones, but because it is difficult to find authors who are willing to write about areas outside those pursued in their own laboratories. Anyone who takes on the task of reviewing a broad area of interest must weave together its various parts by picking up the threads from many different laboratories, and attempt to produce a fabric with a meaningful design. Finding persons who are likely to succeed in such a task was the most difficult part of our job. In the first volume of this treatise, most of the chapters dealt with the mechanisms of The second volume involved a somewhat regulation of gene expression in microorganisms. broader area, spanning the prokaryotic-eukaryotic border. Topics ranged from phage mor phogenesis to the role of gradients in development. The last volume-Volume 3A-con cerned hormones, as does this volume-Volume 3B.

In this brief, Vladimir Uversky discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). Beginning with an introduction to the concept of protein intrinsic disorder, Uversky then goes on to describe the peculiar amino acid sequences of IDPs, their structural heterogeneity, typical functions and disorder-based binding modes. In the final sections, Uversky discusses IDPs in human diseases and as potential drug targets. This volume provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.

The Symposium on "Protein Metabolism: Infiuence of Growth Hormone, Anabolie Steroids, and Nutrition in Health and Disease" is the fourth in the series of International Symposia sponsored by CIBA Limited, Basle. As in the case of the previous conferences, it was planned and organised with the help of experts in the field concerned. Special thanks are due to Prof. A. QuERIDO and Dr. A. A. H. KAssENAAR who, once the idea of the Symposium had been conceived in the course of joint discussions, embarked upon the project with enthusiasm and inspiration, although they must have known full weil what a great deal of time and trouble the organisation of such a meeting would inevitably cost them. For their untiring efforts, for the judicious manner in which they contrived to select precisely those subjects on which interest is chiefiy centred today, and-last but not least-for their success in finding competent specialists to participate in the proceedings, we wish to assure them of our sincere gratitude. To all the members of the Department of Clinical Endocrinology and Diseases of Metabolism, at the University Hospital in Leyden, who helped in preparing the meeting, we would likewise extend a warm vote of thanks. The fact that the present volume, featuring the papers and discussions of the Symposium, has been published only a few months after the event, was made possible thanks to the co operative help of all who participated.

This SpringerBrief explores the physiological roles of Skp1-Cullin1-F-box Complex (SCF) and Anaphase Promoting Complex (APC) in normal cells and in tumor formation. These two related, multi-subunit E3 ubiquitin ligase enzymes, APC and SCF are thought to be the major driving forces governing proper cell cycle progression. Defective cell cycle regulation leads to genomic instability and ultimately, cancer development. Selective degradation of key cell cycle regulators by the ubiquitin-proteasome system has been proven to be a major regulatory mechanism for ensuring ordered and coordinated cell cycle progression. The SCF and APC E3 ligases have been characterized to play pivotal roles in regulating the cell cycle progression by timely degrading various critical cell cycle regulators. This Brief reviews recent studies that have shown that deregulation of signaling pathways in which the two ubiquitin ligases are involved causes aberrant cell cycle regulation, in turn leading to tumorigenesis. The text also discusses how SCF and APC may present promising therapeutic targets to treat various cancers.

It was the year of 1969 when this monograph was originally published in Japanese by Professor TADASHI KAWAI, titled as "The Plasma Proteins, Their Fundamental and Clinical Aspects." After I read through the Japanese edition, I was impressed by its rather complete coverage of the subjects and their detailed descriptions. I have felt that this excellent monograph should be distributed not only among our Japanese scien tists but also among many other colleagues throughout the world. I am happy, the refore, to know that the English edition of his monograph, partly revised, is ready to be published at this time. Professor KAWAI received his postgraduate medical training in U.S.A. for seven years, and was certified by the American Board of Pathology in both Anatomical and Clinical Pathology in Fall, 1962. Thus, I believe, he is the most suitable fellow for publishing the English edition of this kind.

Cancerremainstobeoneofthemostdevastatingdiseasesworldwidesincelong ago. Thepoorprognosisofcancerislargelyduetometastasis. Metastasisisoften depictedasamultistageprocessinwhichmalignantcellsspreadfromtheprimary locustodistantorgansviacirculation. Whereasgeneticalterationsweresuggested tobeessentialfortransformationofprimarytumorcellsintometastaticphenotype, epigeneticeventsareequallyimportant,whichmaybetriggeredbymetastaticf- torswhereverintheprimarytumorlocus,bloodcirculationandthesecondaryloci. Signaltransductionsinitiatedbythemetastaticfactorsareresponsibleformediating themolecularandcellularprocessesleadingtometastasis. Blockadeoftherelevant molecularpathwaysisoneofthemosteffectivestrategiesforpreventionoftumor metastasis. Clinicaltrialsareunderwaywithpromisingoutcome. Inthisbook, wetakecomprehensive review inregard withthisexciting eld ofcancerresearch. Chapter1takesabriefoverviewofrecentlyidenti edsignal mechanismsforeachstepoftumormetastasisincludingtheinitiationstage,intra- sation,anti-anoikisinbloodcirculation,homing,extravasationand nalsurvivalin themetastaticsite. Chapter2makesacompletedreviewforthemolecularandcel- lareventsinvolvedininitiationofmetastasis. Especially,thesignalingmechanisms formediatingtumorprogressioninducedbysomeimportantmetastaticfactorsare described. InChapters3and4,thecentralrolesofMAPKanditsdownstreameff- torsMAPKAPKplayineachstepoftumormetastasisarewelldelineated. Chapter5 furtherdescribesdetailedlyabouthowGrb2andotheradaptorproteins,upstreamof MAPK cascade, contribute tometastasis. InChapter 6, therole ofreactive o- genspecies(ROS)intumorprogressionarehighlighted. Moreover,thepotential contribution of ROS to cross talk between major signaling cascades that lead to sustainedMAPKactivationareproposedinChapter7. Chapter8takesaninsight intothesignalingmechanismsfordynamictraf ckingandturnoveroffocalad- sionproteinsinregulationoftractionandretractionforces,whichareneededfor celllocomotionandinvasion. Chapter9describestheinvolvementofNotchsign- ingpathwaywhichisnotonlyessentialforembryonicdevelopmentbutalsoplays importantroleintumorprogression. Chapter10reviewedtherecentlyidenti ed cancer- and metastasis-initiating cells involved in tumor progression. Especially, signal pathways that are frequently deregulated in cancer stem/progenitor cells v vi Preface duringcancerprogressionarehighlighted. Chapter11describestheroleoflipid rafts, a special component within membrane lipid domain, in signal transd- tion triggered by growth factor receptors leading to tumor metastasis. Finally, Chapters12,Chapters13,andChapters14presentthesignalingpathwaysresp- sibleformetastaticprogressionofspeci ctumorsincludingovariancancer,uveal melanomaandhepatoma,respectively. WethankallthecontributorsofeveryChapterinthebookincludingJia-RuWu, Chi-TanHu,LaureVoisin,StephanieDuhamel,SylvainMeloche,AlexeyShiryaev, MarijkeVanGhelue,UgoMoens,AlessioGiubellino,PraveenR. Arany,Moulay A. Alaoui-Jamali, Krikor Bijian, Panagiota Toliopoulos, Pingyu Zhang, Patrick A. Zweidler-McKay,MurielleMimeault,SurinderK. Batra,SamirKumarPatra, LydiaW. T. Cheung,CarmanK. M. Ip,AliceS. T. Wong,CecileLaurent,Jerome Couturier,XavierSastre-Garau,LaurenceDesjardins,EmmanuelBarillot,Sophie Piperno-Neumann,SimonSauleandRajagopalN. Aravalli. Wehopethisbookmightstimulatemorecancerbiologiststoemphasizethis eld whichbene tsdevisingmoreeffectivemoleculartargetingstrategiesforprevention ofcancermetastasis. Hualien,Taiwan Wen-ShengWu Chi-TanHu Contents 1 Overview of Signal Transduction in Tumor Metastasis...1 Wen-ShengWuandJia-RuWu 2 Microenvironment Triggers EMT, Migration and Invasion of Primary Tumor via Multiple Signal Pathways ...9 Wen-ShengWuandChi-TanHu 3 The ERK1/2 MAP Kinase Signaling Pathway in Tumor Progression and Metastasis ...25 LaureVoisin,StephanieDuhamel,andSylvainMeloche 4 Mitogen-Activated Protein Kinase-Activated Protein Kinases and Metastasis...41 AlexeyShiryaev,MarijkeVanGhelue,andUgoMoens 5 Grb2 and Other Adaptor Proteins in Tumor Metastasis ...77 AlessioGiubellinoandPraveenR. Arany 6 The Role of ROS Signaling in Tumor Progression...103 Wen-ShengWuandJia-RuWu 7 Signal Cross Talks for Sustained MAPK Activation and Cell Migration Mediated by Reactive Oxygen Species: The Involvement in Tumor Progression...

Application of NMR and Molecular Docking in Structure-Based Drug Discovery, by Jaime L. Stark and Robert Powers NMR as a Unique Tool in Assessment and Complex Determination of Weak Protein-Protein Interactions, by Olga Vinogradova and Jun Qin The Use of Residual Dipolar Coupling in Studying Proteins by NMR, by Kang Chen und Nico Tjandra NMR Studies of Metalloproteins, by Hongyan Li and Hongzhe Sun Recent Developments in 15N NMR Relaxation Studies that Probe Protein Backbone Dynamics, by Rieko Ishima Contemporary Methods in Structure Determination of Membrane Proteins by Solution NMR, by Tabussom Qureshi and Natalie K. Goto Protein Structure Determination by Solid-State NMR, by Xin Zhao Dynamic Nuclear Polarization: New Methodology and Applications, by Kong Hung Sze, Qinglin Wu, Ho Sum Tse and Guang Zhu

-Lignin Structure, Properties, and Applications By H. Hatakeyama, T. Hatakeyama -Tensile Mechanics of -Helical Coil Springs By A. Ikai -Bioactive Polymer/Hydroxyapatite (Nano)composites for Bone Tissue Regeneration By K. Pielichowska, S. Blazewicz"