SpringerBriefs in Biochemistry and Molecular Biology – serie

This Brief describes the concept and realization of gene therapy for HIV from the unique historic perspective and insight of two pioneers of the clinical applications of stem cell gene therapy for HIV.Gerhard Bauer applied ribozyme-anti-HIV and other vectors to manufacture clinical grade, HIV-resistant hematopoietic stem cells for the first patients that received stem cell gene therapy for HIV, including the first child in the world and the first fully marrow-ablated HIV infected patient. Joseph Anderson developed the most recent and most potent combination anti-HIV lentiviral vectors and pluripotent stem cell applications for HIV gene therapy and tested these in the appropriate in vitro and vivo models, paving the way for novel HIV gene therapy approaches to possibly cure patients.In Gene Therapy for HIV, Bauer and Anderson discuss the unique aspects of this therapy, including its limitations and proper safety precautions and outline a path for a possible functional cure for HIV using stem cell gene therapy based on a cure already achieved with a bone marrow stem cell transplantation performed in Germany using donor stem cells with a naturally arising CCR5 mutation. In addition, the Brief provides a thorough and methodical explanation of the basics of gene therapy, gene therapy vector development, in vitro and in vivo models for HIV gene therapy and clinical applications of HIV gene therapy, including Good Manufacturing Practices.

This SpringerBrief explores unconventional functions of eight different transcription factors and concludes with a discussion of their biological significance and impact, including effects on processes within the cell nucleaus during development and in adult organisms. Chapter One details unconventional functions of the transcription factors  GAGA, HP1, Rb, STAT, ATF-2 and NF-kB.  Surprisingly, all of these transcription factors can be found in association with heterochromatin as well as euchromatin, and in some cases unconventional functions have been demonstrated for these heterochromatin-associated factors. Chapter Two focuses on the unconventional functions of STAT and HP1 and discusses their roles in the promotion of longevity, and in protection from cancer and DNA damage.  Chapter Three explores the biological significance of the findings presented in the first two chapters and considers how global changes in the epigenome brought about by factors such as STAT and HP1 might affect processes within the cell nucleus during development and in adult organisms. This succinct yet thorough SpringerBrief is essential for researchers studying epigenetics, and to instructors of the subject.  It should also appeal to people interested in the control of gene transcription and other processes in the cell nucleus, and to those interested in development.

Gene therapy was conceived during the early and mid part of the 20th century. At first, it was considered a revolutionary biomedical procedure, which could potentially cure any disease for which the molecular bases were understood. Since then, gene therapy has gone through many stages and has evolved from a nearly unrealistic perspective to a real life application. Clinical efficacy in humans was demonstrated at the beginning of this century after its successful application in small-scale clinical trials to cure severe immunodeficiency in children. However, their successes were overshadowed some time later by the occurrence of vector-related leukaemia in a number of treated children. It is in this context that lentiviral vectors have appeared, with improved efficiency and, possibly, increased biosafety. Very recently, the first clinical trials with lentivectors have been carried out with some success. This Brief firstly defines gene therapy, and places lentivectors within this fascinating therapeutic strategy. Then follows a comprehensive description of the development of retroviral and lentiviral vectors and how to specifically target distinct cell types and tissues. The authors also discuss the application of lentivector gene therapy for the treatment of cancer and autoimmune diseases, ending with the application of lentivectors in human gene therapy clinical trials.

Biological O2 sensing probes and measurement techniques were first introduced in the late 80s. In the last 3-5 years they have undergone major development that have made them available and affordable for a broad range of applications in various disciplines of the life and biomedical sciences. These new chemistries and technologies, which are significantly different from the majority of other fluorescence-based probes and detection techniques, have already demonstrated their high utility. This book will provide a systematic overview of the existing and emerging O2 sensing technologies in their different modifications, a practical guide to their rational selection and use, and examples of biological applications/case studies, including details on how to set up and conduct such experiments, troubleshoot and interpret the data.

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.

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 Exterior investigates the diverse facets of the various scales at which we describe protein biophysical and biochemical phenomena. Although these ideas are entirely mathematical, mathematical expositions have been avoided, unless the use of some expressions becomes absolutely obligatory. A first chapter introduce into fractal dimensions, protein exteriors and to methods to study the roughness of surfaces. The main topics covered in the following chapters include: protein-protein interaction interfaces; protein surface-roughness and local shape as well as adhesion on protein and other rough biomolecular surfaces.

There is now compelling evidence that the complexity of higher organisms correlates with the relative amount of non-coding RNA rather than the number of protein-coding genes. Previously dismissed as “junk DNA”, it is the non-coding regions of the genome that are responsible for regulation, facilitating complex temporal and spatial gene expression through the combinatorial effect of numerous mechanisms and interactions working together to fine-tune gene expression. The major regions involved in regulation of a particular gene are the 5’ and 3’ untranslated regions and introns. In addition, pervasive transcription of complex genomes produces a variety of non-coding transcripts that interact with these regions and contribute to regulation. This book discusses recent insights into the regulatory roles of the untranslated gene regions and non-coding RNAs in the control of complex gene expression, as well as the implications of this in terms of organism complexity and evolution.​

Gamma-Glutamyl Transpeptidases (γ-GTs) are members of the N-terminal nucleophile hydrolase superfamily, enzymes that cleave the γ-glutamyl amide bond of glutathione to liberate cysteinylglycine. The released γ-glutamyl group can be transferred to water (hydrolysis) or to amino acids or short peptides (transpeptidation). γ-GT plays a key role in the gamma glutamyl cycle by regulating the cellular levels of the antioxidant glutathione, hence it is a critical enzyme in maintaining cellular redox homeostasis.γ-GT is upregulated during inflammation and in several human tumors, and it is involved in many physiological disorders related to oxidative stress, such as Parkinson’s disease and diabetes. Furthermore, this enzyme is used as a marker of liver disease and cancer. This book covers current knowledge about the structure-function relationship of γ-GTs and gives information about applications of γ-GTs in different fields ranging from clinical biochemistry to biotechnology and biomedicine.​

The book will discuss classes of proteins and their folding, as well as the involvement of bioinformatics in solving the protein folding problem. In vivo and in vitro folding mechanisms are examined, as well as the failures of in vitro folding, a mechanism helpful in understanding disease caused by misfolding. The role of energy landscapes is also discussed and the computational approaches to these landscapes.

Beer is the most popular alcoholic beverage in the world. Yet, behind each glass of beer there is an enormous amount of work invested. If the first image that comes to your mind is the lifting of heavy bags of malt or carrying kegs, guess again! Most of the work involved in brewing is carried out by “microworkers” – yeast and their enzymes! These special helpers are responsible for catalyzing the vast majority of the biochemical reactions occurring in all steps that gradually transform the sugary wort into beer. This book not only provides readers with an overview of the whole biochemical process involved in beer fermentation, but also reviews the latest findings in this delightful field, making it essential reading for both scientists and brewing enthusiasts

This book explores the double coding property of DNA, which is manifested in the digital and analog information types as two interdependent codes. This double coding principle can be applied to all living systems, from the level of the individual cell to entire social systems, seen as systems of communication. Further topics discussed include the ubiquitous problem of logical typing, which reflects our inherent incapacity to simultaneously perceive discontinuity and continuity, the problem of time, and the peculiarities of autopoietic living systems. It is shown that the scientific “truths” that appear to be coherent constructions connecting the scientifically verified observations by the rules of logic are in fact always relative and never absolute.

This book presents the diverse clinical, cellular and molecular manifestations of NF-KB-related genetic diseases. It shows that studying patient-related pathologies affecting the components of the NF-KB signaling pathway offers the opportunity to understand the various functions of NF-KB in humans, complementing studies performed with mouse models. In addition, people treating those patients acquire a deeper understanding of the molecular basis of the pathophysiological processes.

This book has been conceives as a brief introduction to biomembranes physical chemistry for undergraduate students of sciences, and it is particularly dedicated to the lipid-protein membrane interactions. A general introduction is presented in Chapters 1 and 2. The following Chapters, 3 and 4, describe the most accepted theories on lipid-membrane protein interactions as well as the new experimental approaches, in particular, these arose from nano sciences as atomic for microscopy and single molecule force spectroscopy. The book emphasizes the relevance of physical parameters as the lateral surface pressure and the lipid curvature as actors for understanding the physicochemical properties of the biomembranes.

This succinct volume addresses the production of inactive, potentially toxic proteins in the absence of correct protein folding and the resultant neurodegenerative diseases. Other topics include intrinsic disorder in protein structure and function and the effects of molten globules on protein toxicity. This concise and yet thorough text also discusses using toxin structure as a model for studying structural and functional aspects of protein chemistry. Protein Toxins in Modeling Biochemistry, a SpringerBrief, is essential reading for advanced researchers, scientists and advanced graduate students interested in protein chemistry and related areas of biochemistry and molecular science.

This book explores key applications of phage biotechnology and reviews recent advances in phage display technologies. The applications covered were selected on the basis of their significance and representativeness in the field. The small size and enormous diversity of bacteriophages make them ideal candidates for numerous applications across many industries. Since the discovery of phages and the advent of phage display systems, considerable attention has been focused on the development of novel therapeutic and industrial applications. Recent studies combine the genomic flexibility of phages with phage display systems in order to generate modified phages for targeted delivery.

The book describes the individual steps necessary for biomacromolecular fragments analysis, as well as a list of essential software tools. For each step, it also shows corresponding web-based tools in detail and provides practical examples of their use.All tools and databases mentioned in the examples are available free of charge, platform-independent, web-based, user-friendly and do not require a prior IT background to be fully used.

Gap-junction proteins, connexins are important cellular entities that regulate various facets of cellular physiology. The connexins constitute large family of proteins. The present book provides basic overview about various aspects of connexin proteins. The book has tried to touch the fundamental aspects of connexin family. This book will be useful to broad audience that includes under-and post-graduate students, research scholars, clinicians, etc. The reference section at the end of the book will be helpful for those who seek to know deeper details about this family of proteins.

This book is intended as a reference guide for graduate students, postgraduate students and researchers with a basic knowledge of protein chemistry who would like to know more about the biomedical applications of natural proteins to promote healthier lives. The book is divided into ten chapters, each of which explains different natural proteins and their established biomedical applications. The first chapter extensively deals with protein based natural fibers and provides an overview of all protein based fibers currently available.  In turn, chapter two mainly focuses on the biomedical applications of a special class of proteins called Heat Shock Proteins; the biomedical applications of silkworm pupae proteins are dealt in chapter three. Chapter four examines an interesting use of Eri silk fibroin as a biomaterial for Tissue Engineering, while chapter five discusses the key experimental details involved in converting Tasar silk sericin into self-assembled nanoparticles. Chapter six offers brief descriptions of bioactive proteins with respect to their sources, synthesis and applications. Chapter seven is dedicated to Interleukine-8 and its role in human life, while chapter eight addresses the importance of natural proteins in infectious diseases. Chapter nine explores the issue of excess intake of dietary proteins and its adverse effects, and finally, chapter ten discusses the efficiency of drug delivery systems made up of gelatin nanocomposites. The book is above all intended as a valuable resource for students and researchers alike, sparking their curiosity with regard to the applications of natural proteins and motivating them to focus their own energies on the discovery or identification of additional natural proteins for diverse biomedical uses.

This Brief provides a concise review of chaperonopathies, i.e., diseases in which molecular chaperones play an etiologic-pathogenic role. Introductory chapters deal with the chaperoning system and chaperoning teams and networks, HSP-chaperone subpopulations, the locations and functions of chaperones, and chaperone genes in humans. Other chapters present the chaperonopathies in general, including their molecular features and mechanistic classification into by defect, excess, or mistake. Subsequent chapters discuss the chaperonopathies in more detail, focusing on their distinctive characteristics: primary or secondary; quantitative and/or qualitative; structural and hereditary or acquired; genetic polymorphisms; gene dysregulation; age-related; associated with cancer, chronic inflammatory conditions, and autoimmune diseases. The interconnections between the chaperoning and the immune systems in cancer development, chronic inflammation, autoimmunity, and ageing are outlined, which leads to a discussion on the future prospects of chaperonotherapy. The latter may consist of chaperone gene and protein replacement/supplementation in cases of deficiency and of gene or protein blocking when the chaperone actively promotes disease. The last chapter presents the extracellular chaperones and details on how the chaperone Hsp60 is secreted into the extracellular space and, thus, appears in the blood of cancer patients with potential to participate in carcinogenesis and chronic inflammation and autoimmunity. Chaperones as clinically useful biomarkers are mentioned when pertinent. Likewise, guidelines for clinical evaluation of chaperonopathies and for their histopathological and molecular identification are provided throughout. The book also provides extensive bibliography organized by chapter and topic with comments.

The book is dedicated to the topical area of biology and medicine and the role of stress proteins HSP70 in the regulation of intracellular protein homeostasis, signaling transduction and cell protection. The book is divided into chapters, which describe the discovery of HSP70 and its molecular structure, the mechanism of the synthesis and function in normal and damaged cells, examine the role of HSP70 in immunity, cancerogenesis, aging, Alzheimer's disease and cardiac surgery. In this book, the author looks at HSP70 as a factor which prevents the transformation of homeostasis mechanisms of intracellular proteins into a link in the pathogenesis of a disease.

This book intends to be an easy and concise introduction to the field of nuclear magnetic resonance or NMR, which has revolutionized life sciences in the last twenty years. A significant part of the progress observed in scientific areas like Chemistry, Biology or Medicine can be ascribed to the development experienced by NMR in recent times. Many of the books currently available on NMR deal with the theoretical basis and some of its main applications, but they generally demand a strong background in Physics and Mathematics for a full understanding. This book is aimed to a wide scientific audience, trying to introduce NMR by making all possible effort to remove, without losing any formality and rigor, most of the theoretical jargon that is present in other NMR books. Furthermore, illustrations are provided that show all the basic concepts using a naive vector formalism, or using a simplified approach to the particular NMR-technique described. The intention has been to show simply the foundations and main concepts of NMR, rather than seeking thorough mathematical expressions.

This book reviews the main concepts concerning DNA damage due to environmental carcinogens, the effects of DNA damage on DNA replication using a single DNA polymerase or DNA replisome, and the effects of carcinogens on various cell activities. It also introduces the detailed protocols for bypassing DNA damage. As we know, various environmental carcinogens are produced as a result of industry, agriculture, chemical engineering and vehicle exhaust in our daily life. It has been reported that the environmental carcinogens can be connected to tumors and cancer, directly threatening human health. In this regard, DNA replication is highly susceptible to damage. This book provides graduate students and researchers with an overview of the effects of environmental carcinogens on DNA replication and biological activities in cells. It offers important information for research in the areas of biochemistry, cell biology, medicine, toxicology and public health.

Synthetic Biology (SB) is a revolutionary discipline with a vast range of practical applications, but is SB research really based on engineering principles? Does it contributing to the artificial synthesis of life or does it utilise approaches sufficiently advanced to fall outside the scope of biotechnology or metabolic engineering? This volume reviews the development of SB and includes the major milestones of the discipline, the ‘top-down’ and ‘bottom-up’ approaches towards the construction of an artificial cell and the development of the “iGEM” competition. We conclude that SB is an emerging field with extraordinary technological potential, but that most research projects actually are an extension of metabolic engineering since the complexity of living organisms, their tight dependence on evolution and our limited knowledge of the interactions between the molecules, actually make life difficult to engineer.

This book offers an essential introduction for all graduate students and researchers who are working on or interested in mechanotransduction using fruit flies as their model organisms. Designed for accessibility, it follows a simple five-chapter structure, beginning with a general introduction to mechanotransduction in physiology (Chapter 1) and some basic considerations on the principles behind mechanotransduction processes (Chapter 2). In turn, Chapters 3, 4 and 5 focus on mechanoreceptors in Drosophila melanogaster. Chapter 3 explains how the fly’s mechanosensitive cells (i.e. mechanoreceptors) contribute to its daily life, while Chapter 4 explores the ultrastructural and mechanical basis for the working mechanisms of various fly mechanoreceptors. Lastly, Chapter 5 elaborates on the structure, function and physiology of mechanosensitive molecules in fly mechanoreceptors. Accordingly, the book provides an overall framework, helping readers understandmechanosensory transduction, from the physiological level to the molecular level.

This book summarizes the emerging experimental evidence on hair-cell mechanotransduction, and covers hair’s cellular structure, biophysical properties, molecular components and functions. Auditory hair cells convert sound-induced vibration into electrical signals. This biological process, mechanotransduction, is what allows us to hear and communicate in our daily lives. However, our grasp of hair-cell mechanotransduction is still far from complete. Recent advances in molecular genetics and biophysics have helped us gain deeper insights into this process, especially the molecular constituent and operation of the channel complex. This book provides a cutting-edge snapshot for all readers who are interested in or studying how auditory hair cells detect sound.