Methods in protein sequence analysis constitute important fields in rapid progress. We have experienced a continuous increase in analytical sensitivity coupled with decreases in time necessary for purification and analysis. Several generations of sequencers, liquid/solid/gas-phase, have passed by and returned in other shapes during just over two decades. Similarly, the introduction of HPLC permitted an enormous leap forward in this as in other fields of biochemistry, and we now start to see new major advances in purification/analysis through capillary electrophoresis. Furthermore, progress in the field of mass spectrometry has matched that in chemical analysis and we witness continuous development, now emphasizing ion spray and other mass spectrometric approaches. In short, protein analysis has progressed in line with other developments in modern science and constitutes an indispensable, integral part of present-day molecular biology. Even the available molecular tools, in the form of proteases with different specificities, have increased in number, although we still have far to go to reach an array of "restriction proteases" like the sets of nucleases available to the molecular geneticist. Of course, conferences have been devoted to protein sequence analysis, in particular the MPSA (Methods in Protein Sequence Analysis) series, of which the 8th conference took place in Kiruna, Sweden, July 1-6 1990. Again, we witnessed much progress, saw new instruments, and experienced further interpretational insights into protein mechanisms and functions.

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.

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.

Cell surface molecules are critically important in regulating cell structure and function. Recent advances on the functional role of cell surface molecules, particularly glycoconjugates are presented in this book. Comprising of 22 chapters from the 2011 International Symposium on Biochemical Roles of Eukaryotic Cell Surface Macromolecules, it covers topics on the analysis of glycome, biophysical approaches to study cell surface molecules, glycoconjugate metabolism and its dysregulation, and molecular mechanisms involved in cell-cell and cell-matrix interaction.

The book contains chapters written by leaders in the research on the structure and function of respiratory complex I. It will provide a concise and authoritative summary of the current knowledge on complex I of respiratory chains. This enzyme is central to energy metabolism and is implicated in many human neurodegenerative diseases, as well as in aging. Until recently it was poorly understood on a structural level, and this book will provide a timely reference resource. Such a book was not published previously. The last time a minireview series on complex I were published was in 2001, and since then complex I field changed quite dramatically.

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.

Bioinformation Discovery illustrates the power of biological data in knowledge discovery. It describes biological data types and representations with examples for creating a workflow in Bioinformation discovery. The concepts in knowledge discovery from data are illustrated using line diagrams. The principles and concepts in knowledge discovery are used for the development of prediction models for simulations of biological reactions and events. Advanced topics in molecular evolution and cellular & molecular biology are addressed using Bioinformation gleaned through discovery. Each chapter contains approximately 10 exercises for practice. This will help students to expand their problem solving skills in Bioinformation Discovery. Each chapter concludes with a number of good problem sets to test mastery of the material.

Six decades after the serendipitous discovery of chlorpromazine as an antipsychotic and four decades after the launch of clozapine, the first atypical or second generation antipsychotic, psychopharmacology has arrived at an important crossroad. It is clear that pharmacological research and pharmaceutical development must now focus on complementary or even alternative mechanisms of action to address unmet medical needs, i.e. poorly treated domains of schizophrenia, improved acceptance by patients, better adherence to medication, safety in psychoses in demented patients, and avoiding cardiac and metabolic adverse effects. The first completely novel mechanisms evolving from our insights into the pathophysiology of psychotic disorders, especially the role of glutamatergic mechanisms in schizophrenia, are now under development, and further principles are on the horizon. This situation, in many respects similar to that when the initial second-generation antipsychotics became available, can be rewarding for all. Preclinical and clinical researchers now have the opportunity to confirm their hypotheses and the pharmaceutical industry may be able to develop really novel classes of therapeutics. When we were approached by the publishers of the Handbook of Experimental Pharmacology to prepare a new volume on antipsychotics, our intention was to capture both, the accumulated preclinical and clinical knowledge about current antipsychotics as well as prospects for new and potentially more specific antischizophrenia principles. These efforts should be based on the pathophysiology of the diseases and the affected neurotransmitter systems. Since preclinical research on antipsychotic compounds is only reliable when intimately linked through translational aspects to clinical results, we decided to include clinical science as well. It turned out that that this endeavor could not be covered by a single volume. We thank the editorial board and the publishers for supporting our decision to prepare two volumes: Current Antipsychotics and Novel Antischizophrenia Treatments. These topics cannot really be separated from one another and should be seen as a composite entity despite the somewhat arbitrary separation of contributions into two volumes. The continuing challenges of developing improved and safer antipsychotic medications remain of concern and are discussed in the first volume. The new opportunities for the field to develop and license adjunctive treatments for the negative symptoms and cognitive deficits that are treated inadequately by existing compounds have been incentivized recently and provide the focus for the second volume. We hope these collective contributions will facilitate the development of improved treatments for the full range of symptomatology seen in the group of schizophrenias and other major psychotic disorders. Gerhard Gross, Ludwigshafen, Germany Mark A. Geyer, La Jolla, CA This volume will try to put current therapy - achievements, shortcomings, remaining medical needs - and emerging new targets into the context of increasing knowledge regarding the genetic and neurodevelopmental contributions to the pathophysiology of schizophrenia. Some of the chapters will also deal with respective experimental and clinical methodology, biomarkers, and translational aspects of drug development. Non-schizophrenia indications will be covered to some extent, but not exhaustively.

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.

ABPP Methodology: Introduction and Overview, by Matthew B. Nodwell und Stephan A. Sieber Activity-Based Protein Profiling for Natural Product Target Discovery, by Joanna Krysiak und Rolf Breinbauer Photoaffinity Labeling in Activity-Based Protein Profiling, by Paul P. Geurink, Laurette M. Prely, Gijs A. van der Marel, Rainer Bischoff und Herman S. Overkleeft Application of Activity-Based Protein Profiling to the Study of Microbial Pathogenesis, by William P. Heal und Edward W. Tate Functional Analysis of Protein Targets by Metabolomic Approaches, by Yun-Gon Kim und Alan Saghatelian

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.

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.

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.

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

Sequencing projects have revealed the presence of at least several hundred receptor kinases in a typical plant genome. Receptor kinases are therefore the largest family of primary signal transducers in plants, and their abundance suggests an immense signaling network that we have only just begun to uncover. Recent research findings indicate that individual receptor kinases fulfill important roles in growth and development, in the recognition of pathogens and symbionts or, in a few examples, in both growth and defense. This volume will focus on the roles of receptor kinases, their signaling pathways, and the ways in which these important signaling proteins are regulated.

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."

This work presents the most advanced discoveries from translational research laboratories directly involved in identifying molecules and signalling pathways that play an instrumental role in metastasis. In contrast to other works, conventionally focused on a single type of tumour, the various chapters in this book provide a broad perspective of the similarities and discrepancies among the dissemination of several solid malignancies. Through recurrent and overlapping references to molecular mechanisms and mediators, the readers will gain knowledge of the common ground in metastasis from a single source. Finally, an introductory chapter provides a clinical perspective of the problems presented by metastatic tumours for diagnosis and treatment. The work presented here is directed to researchers in tumour biology with a developing interest in metastatic dissemination as well as medical and graduate students seeking to expand and integrate the notions acquired in basic cancer biology and oncology courses.

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

It can be concluded (under the specific experimental procedures em ployed) that: - 1) HCG labelled with 1 - 2 atoms of radioactive iodine did not differ sig nificantly from the unlabelled hormone; 2) The ovary alone exhibited a capacity to affix specifically HCG; 3) The amount of radioactive material in the ovary was directly proport ional to the quantity of labelled HCG injected; 4) When the HCG present in the circulation is bound to an antiserum to HCG, the antigen-antibody complex is not concentrated by the ovary; 5) Circulating labelled HCG decreased to 50% within 30 minutes following a single intravenous injection; 6) There are four different phases of ovarian uptake of HCG, namely: the first phase, when there is only an inflow from the circulation and stor age mainly in the follicular envelopes; the second phase, when there is a greater inflow than outflow; the third phase, when the inflow is equal to the outflow; and the fourth period, when the outflow is bigger than the in flow. REFERENCES 1. Lunenfeld, B. and Eshkol, A. Vitamins and Hormones (1967) 25:165 2. Eshkol, A. In: Recent Research on Gonadotropbio Hormones, eds. E. T. Bell andJ. A. Loraine, Edinburgh, Livingstone (1967), p. 202. 3. Eshkol, A. and Lunenfeld, B. Proc. Tel-Hashomer Hosp. (1967) 6:4. ACKNOWLEOOMEN'IS This work was supported in part by a grant from the Population Council, N. Y., U. S. A. andbyGrantNo."

Lactoferrin is an iron-binding glycoprotein belonging to the transferrin family. It acts as a defense in host animals against microbes and viruses, since it has a broad spectrum of antimicrobial and antiviral activities. Lactoferrin has been shown to regulate the growth and differentiation of many types of cells. The results of recent studies indicate that lactoferrin is a potent regulator of dermal fibroblasts, and promotes cutaneous wound healing. The collagen gel contraction, a model of wound contraction during wound healing process, and migration of human fibroblasts were enhanced by lactoferrin. LRP-1 (LDL Receptor related Protein-1) acts as a signaling receptor for lactoferrin that mediate fibroblast response to lactoferrin by activating ERK/MAPK signaling pathway. In addition, lactoferrin promotes biosynthesis of extracellular matrix (ECM) component such as type-I collagen and hyaluronan. Hyaluronan is a major component of ECM in connective tissue and promotes wound healing. The promoting effect of lactoferrin on hyaluronan production was accompanied by promotion of HAS2 (hyaluronan synthase 2) expression. These observations suggest that lactoferrin promotes the wound healing by providing an ECM that promotes fibroblast migration. Lactoferrin is also known for its anti-inflammatory and immune modulating properties. According to recent in vivo study, lactoferrin promotes wound repair by promoting the early inflammatory phase of wound healing. Based on this, recombinant human lactoferrin was subsequently tested clinically in a Phase II trial in patients with diabetic ulcers and was found to be effective. Lactoferrin should be further evaluated in patients with diabetic and other types of ulcers.

The book highlights work from many different labs that taught us abnormal HDACs potentially contribute to the development or progression of many human diseases including immune dysfunctions, heart disease, cancer, memory impairment, aging, and metabolic disorders.

Infrared spectroscopy is a new and innovative technology to study protein folding/misfolding events in the broad arsenal of techniques conventionally used in this field. The progress in understanding protein folding and misfolding is primarily due to the development of biophysical methods which permit to probe conformational changes with high kinetic and structural resolution. The most commonly used approaches rely on rapid mixing methods to initiate the folding event via a sudden change in solvent conditions. Traditionally, techniques such as fluorescence, circular dichroism or visible absorption are applied to probe the process. In contrast to these techniques, infrared spectroscopy came into play only very recently, and the progress made in this field up to date which now permits to probe folding events over the time scale from picoseconds to minutes has not yet been discussed in a book. The aim of this book is to provide an overview of the developments as seen by some of the main contributors to the field. The chapters are not intended to give exhaustive reviews of the literature but, instead to illustrate examples demonstrating the sort of information, which infrared techniques can provide and how this information can be extracted from the experimental data. By discussing the strengths and limitations of the infrared approaches for the investigation of folding and misfolding mechanisms this book helps the reader to evaluate whether a particular system is appropriate for studies by infrared spectroscopy and which specific advantages the techniques offer to solve specific problems.

There are nearly 100 000 different protein sequences encoded in the human genome, each with its own specific fold. Understanding how a newly formed polypeptide sequence finds its way to the correct fold is one of the greatest challenges in the modern structural biology. The aim of this thesis is to provide novel insights into protein folding by considering the problem from the point of view of statistical mechanics. The thesis starts by investigating the fundamental degrees of freedom in polypeptides that are responsible for the conformational transitions. This knowledge is then applied in the statistical mechanics description of helix coil transitions in polypeptides. Finally, the theoretical formalism is generalized to the case of proteins in an aqueous environment. The major novelty of this work lies in combining (a) a formalism based on fundamental physical properties of the system and (b) the resulting possibility of describing the folding unfolding transitions quantitatively. The clear physical nature of the formalism opens the way to further applications in a large variety of systems and processes.

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.