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This thesis presents a method for reliably and robustly producing samples of amyloid-β (Aβ) by capturing them at various stages of aggregation, as well as the results of subsequent imaging with various atomic force microscopy (AFM) methods, all of which add value to the data gathered by collecting information on the peptide’s nanomechanical, elastic, thermal or spectroscopical properties. Amyloid-β (Aβ) undergoes a hierarchy of aggregation following a structural transition, making it an ideal subject of study using scanning probe microscopy (SPM), dynamic light scattering (DLS) and other physical techniques. By imaging samples of Aβ with Ultrasonic Force Microscopy, a detailed substructure to the morphology is revealed, which correlates well with the most advanced cryo-EM work. Early stage work in the area of thermal and spectroscopical AFM is also presented, and indicates the promise these techniques may hold for imaging sensitive and complex biological materials. This thesis demonstrates that physical techniques can be highly complementary when studying the aggregation of amyloid peptides, and allow the detection of subtle differences in their aggregation processes.
Forensic Microscopy: Truth Under the Lenses provides an overview and understanding of the various types of microscopes and their techniques employed in forensic science. The book emphasizes both the theoretical and practical aspects of microscopy to enrich the reader’s understanding of the various tools, techniques, and utility—including strengths and weaknesses—of types of microscopes in analyzing certain forms of evidence. The book begins with the history of microscopes, the basic optics for microscopy, then moves to advanced microscopies such as electron microscopes and atomic force microscopes. In addition to the various types of microscopes and how to use and best utilize them, the book looks at the analysis of specific types of evidence, including hair, fiber, fingerprint, body fluids, tool marks, ink, pollen grains, spores, diatoms, bullets, cartridges, among other evidence types. Since forensic science is an applied, hands-on discipline, the book includes both a theoretical and a practical approach to the topic. Key Features: Addresses simple to advanced microscopy techniques for the effective analyses of trace evidence Pairs chapters on a particular type of microscopy, explaining it thoroughly, before delving into specific usage for forensic applications Presents theories and as well as real-world application of concepts Provides abundant micro-photographs, including graphical representations and flow charts, to illustrate concepts clearly Forensic Microscopy serves as a helpful reference for undergraduate and postgraduate students in forensic science, forensic biology, forensic chemistry and related programs. It is also recommended for research students, academicians, technicians, industry and laboratory professionals working on trace evidence analysis.
This volume presents readers with the latest techniques to study nanoimaging and nanoprobing in application to a broad range of biological systems. The chapters in this book are divided into five parts, and cover topics such as imaging and probing of biomacromolecules including high-speed imaging and probing with AFM; probing chromatin structure with magnetic tweezers; and fluorescence correlation spectroscopy on genomic DNA in living cells. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and through, Nanoscale Imaging: Methods and Protocols is a valuable resource for anyone interested in learning more about this developing and expanding field.
Comprehensive Medicinal Chemistry III, Eight Volume Set provides a contemporary and forward-looking critical analysis and summary of recent developments, emerging trends, and recently identified new areas where medicinal chemistry is having an impact. The discipline of medicinal chemistry continues to evolve as it adapts to new opportunities and strives to solve new challenges. These include drug targeting, biomolecular therapeutics, development of chemical biology tools, data collection and analysis, in silico models as predictors for biological properties, identification and validation of new targets, approaches to quantify target engagement, new methods for synthesis of drug candidates such as green chemistry, development of novel scaffolds for drug discovery, and the role of regulatory agencies in drug discovery. Reviews the strategies, technologies, principles, and applications of modern medicinal chemistry Provides a global and current perspective of today's drug discovery process and discusses the major therapeutic classes and targets Includes a unique collection of case studies and personal assays reviewing the discovery and development of key drugs
Vibrational Spectroscopy in Protein Research offers a thorough discussion of vibrational spectroscopy in protein research, providing researchers with clear, practical guidance on methods employed, areas of application, and modes of analysis. With chapter contributions from international leaders in the field, the book addresses basic principles of vibrational spectroscopy in protein research, instrumentation and technologies available, sampling methods, quantitative analysis, origin of group frequencies, and qualitative interpretation. In addition to discussing vibrational spectroscopy for the analysis of purified proteins, chapter authors also examine its use in studying complex protein systems, including protein aggregates, fibrous proteins, membrane proteins and protein assemblies. Emphasis throughout the book is placed on applications in human tissue, cell development, and disease analysis, with chapters dedicated to studies of molecular changes that occur during disease progression, as well as identifying changes in tissues and cells in disease studies. - Provides thorough guidance in implementing cutting-edge vibrational spectroscopic methods from international leaders in the field - Emphasizes in vivo, in situ and non-invasive analysis of proteins in biomedical and life science research more broadly - Contains chapters that address vibrational spectroscopy for the study of simple purified proteins and protein aggregates, fibrous proteins, membrane proteins and protein assemblies
Frontiers in Nanomedicine offers an up-to-date understanding of nanomaterials to readers having clinical or biomolecular research interests. Scientists, both aspiring and experienced, will find, in each volume, a comprehensive overview of current molecular strategies for using nanoscale materials in medicine. This volume explains the use of nanotechnology in medicine to improve the diagnosis of disease and the role of nanoparticles in targeted drug delivery systems for theranostic applications. This volume also covers the applications of nanoparticles in breast cancer research, liver disease therapy and Alzheimer’s disease treatment.
This book offers significant coverage on different aspects of cancer from risk factors to the mechanisms leading to tumor progression and metastasis. Although tremendous progress has been made in cancer research and treatment, cancer metastasis remains a major unmet clinical need. The life and death of many cancer patients hangs on the degree of metastasis. This book provides new perspectives for diagnosis and cancer therapy. It includes new technologies and a new basis for current cancer therapies. To guarantee the high quality of this book, important topics are included and rigorously discussed in a simple and authentic way. The book addresses important challenges governing tumor progression and metastasis and brings new responses to both diagnosis and therapy. This book is a great source of knowledge and will be useful for researchers, medical doctors, oncologists, graduate and medical students, continued medical educators, health care providers, and all individuals interested in understanding cancer and its challenges.
Peptide Catalysts, including Catalytic Amyloids, Volume 697 in this esteemed series, highlights new advances in the field, with this new volume presenting interesting topics on Screening of oxidative behaviors in catalytic amyloid assemblies, Catalytic amyloids derived for natural proteins, AFM-IR studies of catalytic amyloids, MD structural studies of catalytic amyloids, Characterization of crystalline, amyloid-like amino acid assemblies, Computational modeling of supramolecular peptide assemblies, and Assembly and activity of short prion-inspired peptides. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in Methods in Enzymology series - Updated release includes the latest information on Peptide Catalysts, including Catalytic Amyloids
Bio-Nanoimaging: Protein Misfolding & Aggregation provides a unique introduction to both novel and established nanoimaging techniques for visualization and characterization of misfolded and aggregated protein species. The book is divided into three sections covering: - Nanotechnology and nanoimaging technology, including cryoelectron microscopy of beta(2)-microglobulin, studying amyloidogensis by FRET; and scanning tunneling microscopy of protein deposits - Polymorphisms of protein misfolded and aggregated species, including fibrillar polymorphism, amyloid-like protofibrils, and insulin oligomers - Polymorphisms of misfolding and aggregation processes, including multiple pathways of lysozyme aggregation, misfolded intermediate of a PDZ domain, and micelle formation by human islet amyloid polypeptide Protein misfolding and aggregation is a fast-growing frontier in molecular medicine and protein chemistry. Related disorders include cataracts, arthritis, cystic fibrosis, late-onset diabetes mellitus, and numerous neurodegenerative diseases like Alzheimer's and Parkinson's. Nanoimaging technology has proved crucial in understanding protein-misfolding pathologies and in potential drug design aimed at the inhibition or reversal of protein aggregation. Using these technologies, researchers can monitor the aggregation process, visualize protein aggregates and analyze their properties. - Provides practical examples of nanoimaging research from leading molecular biology, cell biology, protein chemistry, biotechnology, genetics, and pharmaceutical labs - Includes over 200 color images to illustrate the power of various nanoimaging technologies - Focuses on nanoimaging techniques applied to protein misfolding and aggregation in molecular medicine
The Handbook of Computational Neurodegeneration provides a comprehensive overview of the field and thus bridges the gap between standard textbooks of research on neurodegeneration and dispersed publications for specialists that have a narrowed focus on computational methods to study this complicated process. The handbook reviews the central issues and methodological approaches related to the field for which the reader pursues a thorough overview. It also conveys more advanced knowledge, thus serving both as an introductory text and as a starting point for an in-depth study of a specific area, as well as a quick reference source for the expert by reflecting the state of the art and future prospects. The book includes topics that are usually missing in standard textbooks and that are only marginally represented in the specific literature. The broad scope of this handbook is reflected by five major parts that facilitate an integration of computational concepts, methods and applications in the study of neurodegeneration. Each part is intended to stand on its own, giving an overview of the topic and the most important problems and approaches, which are supported by examples, practical applications, and proposed methodologies. The basic concepts and knowledge, standard procedures and methods are presented, as well as recent advances and new perspectives.