This book presents a comprehensive discussion on the heterogeneity existing between different types of stem cells within the same tissue, for several types of cancers, e.g. glioblastoma stem cells. Recent developments have revealed completely different roles of distinct stem cells within the same organ. Thus, Stem Cells Heterogeneity in Cancer provides a timely update us on the current information on stem cells heterogeneity in various tissues. It also provides a solid foundation of the history of stem cells from specific tissues and the current applications of this knowledge in regenerative medicine. When taken as a whole, alongside its companion volumes Stem Cells Heterogeneity - Novel Concepts, and Stem Cells Heterogeneity in Different Organs, these three books present a comprehensive reference on stem cell heterogeneity in various tissues and current and future applications for regenerative medicine. It is essential reading for advanced cell biology students as well as researchers in stem cells and clinicians.

This book focuses on the mechanobiological principles in tissue engineering with a particular emphasis on the multiscale aspects of the translation of mechanical forces from bioreactors down to the cellular level. The book contributes to a better understanding of the design and use of bioreactors for tissue engineering and the use of mechanical loading to optimize in vitro cell culture conditions. It covers experimental and computational approaches and the combination of both to show the benefits that computational modelling can bring to experimentalists when studying in vitro cell culture within a scaffold. With topics from multidisciplinary fields of the life sciences, medicine, and engineering, this work provides a novel approach to the use of engineering tools for the optimization of biological processes and its application to regenerative medicine. The volume is a valuable resource for researchers and graduate students studying mechanobiology and tissue engineering. For undergraduate students it also provides deep insight into tissue engineering and its use in the design of bioreactors. The book is supplemented with extensive references for all chapters to help the reader to progress through the study of each topic.

Leading researchers are specially invited to provide a complete understanding of the key topics in these archetypal multidisciplinary fields. In a form immediately useful to scientists, this periodical aims to filter, highlight and review the latest developments in these rapidly advancing fields.

This volume details a comprehensive and extensive set of protocols for the study of autophagy in vitro and in vivo. Chapters focus on mammals, various model organisms, and provide protocols for the study of autophagy-related processes outside of the canonical autophagy pathways. 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. Authoritative and cutting-edge, Autophagy: Methods and Protocols aims to ensure successful results in the further study of this vital field.

Recent advances in protein structural biology, coupled with new developments in human genetics, have opened the door to understanding the molecular basis of many metabolic, physiological, and developmental processes in human biology. Medical pathologies, and their chemical therapies, are increasingly being described at the molecular level. For single-gene diseases, and some multi-gene conditions, identification of highly correlated genes immediately leads to identification of covalent structures of the actual chemical agents of the disease, namely the protein gene products. Once the primary sequence of a protein is ascertained, structural biologists work to determine its three-dimensional, biologically active structure, or to predict its probable fold and/or function by comparison to the data base of known protein structures. Similarly, three-dimensional structures of proteins produced by microbiological pathogens are the subject of intense study, for example, the proteins necessary for maturation of the human HIV virus. Once the three-dimensional structure of a protein is known or predicted, its function, as well as potential binding sites for drugs that inhibit its function, become tractable questions. The medical ramifications of the burgeoning results of protein structural biology, from gene replacement therapy to "rational" drug design, are well recognized by researchers in biomedical areas, and by a significant proportion of the general population. The purpose of this book is to introduce biomedical scientists to important areas of protein structural biology, and to provide an insightful orientation to the primary literature that shapes the field in each subject.
The chapters in this volume cover aspects of protein structural biology which have led to the recognition of fundamental relationships between protein structure and function.

Every time a cell divides, a copy of its genomic DNA has to be faithfully copied to generate new genomic DNA for the daughter cells. The process of DNA replication needs to be precisely regulated to ensure that replication of the genome is complete and accurate, but that re-replication does not occur. Errors in DNA replication can lead to genome instability and cancer. The process of replication initiation is of paramount importance, because once the cell is committed to replicate DNA, it must finish this process. A great deal of progress has been made in understanding how DNA replication is initiated in eukaryotic cells in the past ten years, but this is the first one-source book on these findings. The Initiation of DNA Replication in Eukaryotes will focus on how DNA replication is initiated in eukaryotic cells. While the concept of replication initiation is simple, its elaborate regulation and integration with other cell processes results in a high level of complexity. This book will cover how the position of replication initiation is chosen, how replication initiation is integrated with the phases of the cell cycle, and how it is regulated in the case of damage to DNA. It is the cellular protein machinery that enables replication initiation to be activated and regulated. We now have an in-depth understanding of how cellular proteins work together to start DNA replication, and this new resource will reveal a mechanistic description of DNA replication initiation as well.

This book will provide current understandings about two ubiquitously expressed metabotropic GPCRs, G-coupled purinoreceptor type 2 (P2Y) and Takeda G-protein-coupled bile acid receptor 5 (TGR5). G protein coupled receptors (GPCRs) are the largest family of proteins implicated in majority of cellular responses. The two receptor sub-families play a central role in many physiological functions as well as in many pathological conditions. This book offers up-to-date information on the physiological functions, signaling pathways and regulatory mechanisms of P2Y and TGR5 receptors. In addition, this book provides a comprehensive overview about the abnormalities of P2Y/TGR5 receptors and their contribution in the development and progression of pathological conditions. It also covers the currently available natural, chemical and pharmacological agents targeting these two receptor families and their therapeutic implications in P2Y and TGR5 associated disorders. This book is a valuable source for beginners and researchers to follow the rapidly progressing field of these two GPCR subfamily members.

Sox2: Biology and Role in Development and Disease offers a thorough discussion of the important role of Sox2 in cellular and developmental processes, aimed at facilitating greater understanding of how Sox2 functions across different disciplines. The book discusses the basic biology of Sox2 to help establish the critical foundational knowledge necessary for deeper molecular and functional analysis. The book also provides insight into how the Sox2 transcription factor plays a key role in pluripotency induction, maintenance, and development. Helpful as a tool to organize new research projects, the book assists with preparing lessons, seminars, and thesis or research papers, thereby circumventing the need to spend hours searching through journal databases. A single source for the basic biology of Sox2, Sox2: Biology and Its Role in Development and Disease provides information on networks, gene regulation, and regulatory function in a number of cell types and tissues types.

This book shares the latest research and practice-oriented findings in medical sciences with a wide audience. It addresses a range of contemporary issues, often unresolved or contentious, across various medical fields, including advances in the management of hemorrhagic brain stroke. It also discusses metastatic renal cell carcinoma - a global scourge with an extremely poor long-term survival prognosis, the course and sequelae of renal cell carcinoma, as well as advances in targeted molecular therapy with sunitinib, a receptor tyrosine kinase inhibitor. Further, it examines the molecular targeting of proliferative signaling of the epidermal growth factor receptor in the first-line treatment of patients with metastatic non-small-cell lung cancer. Other articles cover clearance of toxins in hemodialyzed patients; the search for diagnostic and therapeutic markers in the connective tissue disease scleroderma; obesity linked to inappropriate dietary habit; clinical problems related to the diagnosis of sensitization to fungi and its role in asthma; and reasons for the perilous trend of avoiding basic vaccinations in children. Lastly, the book explores the rapid developments in e-health technologies that increase access to health services, particularly for the elderly. The book is intended for clinical specialists, researchers, and all allied health professionals from various fields.

This is the second volume in a series on membrane protein transfer. Membrane protein transport underlies the topological disposition of many proteins within cells and it is this disposition that allows for the co-ordination of the central cellular processes, such as metabolism.

Now poised to evaluate the potential in modulating Wnt signaling for therapeutic agendas in cancer, wound healing, and degenerative disease, this book collects protocols from an exciting area of study. The methodologies include using Wnt modulating chemicals in engineering tissues from induced pluripotent and embryonic stem cells, monitoring Wnt transcriptional responses in diverse tissues such as bone and skin, and using specific biochemical markers of Wnt signaling to either screen molecular libraries or evaluate novel reagents. These protocols also leverage unique experimental strengths from five different model organisms. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and authoritative, Wnt Signaling: Methods and Protocols aims to support researchers in understanding Wnt signal transduction in any effort to improve outcomes in regenerative medicine and cancer management.

Understanding the dynamics of cell and tissue motion forms an essential step in understanding the dynamics of life and biological self-organization. Biological motion is one of the most obvious expressions of self-organization, as it requires autonomous creation and regulated action of forces leading to shape formation and translocation of cells and tissues. The topics of the book include intracellular motility and cytoplasma dynamics (e.g. cell division), single cell movement in varying extracellular media (e.g. chemotaxis or contact guidance), cell aggregation and cooperative motion (e.g. cellular swarms or slugs) and, finally, cell-cell interactions in developing tissues (e.g. embryogenesis or plant movement). The dynamics underlying biological motion are explained, on the one hand, by various methods of image processing and correlation analysis, and on the other hand by using physico-chemical theories, developing corresponding mathematical models and performing continuum field or stochastic simulations. Thus, the study is of an interdisciplinary character typically found in theoretical and mathematical biology. Its presentation is intended to reach a broad audience a " from theoretically interested bioscientists, physicians and biophysicists to applied mathematicians interested in the application of nonlinear dynamical systems and simulation algorithms. The most important feature of the book is that it considers possible synergetic mechanisms of interaction and cooperation on different microscopic levels: on the molecular level of cytoskeletal polymers, membrane proteins and extracellular matrix filaments, as well as on the level of cells and cellular tissues. New results concern the aspects of filament or cell alignment, various modes of force transduction and the formation of global stress fields. The latter aspect of mechanical cell-cell communication is emphasized in order to complement the much more well-studied phenomena of chemical, genetical or electrophysical communication.

This detailed book collects new and updated techniques that will help to improve our understanding of the mechanisms underlying stem cell-derived repair through stem cells of the epidermal and dermal lineages, which have led to the isolation of numerous stem cell-like sub-populations from the epidermis and dermis. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Skin Stem Cells: Methods and Protocols, Second Edition serves as a valuable assemblage of protocols for researchers both already working in the field and those who now wish to newly embark on studies of skin stem cells.

This book is a compilation of past and recent knowledge in the field of emerging drug resistance. The book covers major aspects of drug resistance in bacteria, fungi, malaria, and cancer.Human survival on earth is constantly threatened by disease and syndrome. From the early days, the aim of research in medicine was to find therapeutic agents that can improve the quality of human life. Although humans are dependent on natural compounds from early days their dependence of drugs increased excessively in last century. The advances in chemistry and biology have helped researchers to identify the drugs that have improved treatment of many diseases. The primary factor for treatment of these diseases is dependent on the efficacy of drugs available. The development of resistance to these drugs is one of the major hindrances. Although there are number of books available on this topic, "drug resistance" biology across kingdoms has never been discussed in a coherent way.

This book discusses cancers and the resurgence of public interest in plant-based and herbal drugs. It also describes ways of obtaining anti-cancer drugs from plants and improving their production using biotechnological techniques. It presents methods such as cell culture, shoot and root culture, hairy root culture, purification of plant raw materials, genetic engineering, optimization of culture conditions as well as metabolic engineering with examples of successes like taxol, shikonin, ingenol mebutate and podophylotoxin. In addition, it describes the applications and limitations of large-scale production of anti-cancer compounds using biotechnological means. Lastly, it discusses future economical and eco-friendly strategies for obtaining anti-cancer compounds using biotechnology.

Soil salinity is a key abiotic-stress and poses serious threats to crop yields and quality of produce. Owing to the underlying complexity, conventional breeding programs have met with limited success. Even genetic engineering approaches, via transferring/overexpressing a single 'direct action gene' per event did not yield optimal results. Nevertheless, the biotechnological advents in last decade coupled with the availability of genomic sequences of major crops and model plants have opened new vistas for understanding salinity-responses and improving salinity tolerance in important glycophytic crops. Our goal is to summarize these findings for those who wish to understand and target the molecular mechanisms for producing salt-tolerant and high-yielding crops. Through this 2-volume book series, we critically assess the potential venues for imparting salt stress tolerance to major crops in the post-genomic era. Accordingly, perspectives on improving crop salinity tolerance by targeting the sensory, ion-transport and signaling mechanisms are presented here in volume 1. Volume 2 will focus on the potency of post-genomic era tools that include RNAi, genomic intervention, genome editing and systems biology approaches for producing salt tolerant crops.

This volume is the result of an explosion of molecular-based research on Cilia, which began with the discovery of the universality of intraflagellar transport (IFT) and ciliary genomics/proteomics. The chapters in this book cover topics such as: high resolution imaging and functional characterization of sensory and primary cilia in mammalian cells and zebrafish, methods to study ciliary-mediated chemoresponse in Paramecium, and methods to study centrosomes and cilia in C. elegans and Drosophila. Written in the highly successful Methods in Molecular Biology series format, chapters include introduction to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and cutting-edge, Cilia: Methods and Protocols is broad and covers motile, sensory, and primary cells. It is a valuable resource to anyone interested in entering the field of ciliary biology using model organisms, including flagellate algae, ciliates, planaria, nematodes, insects, zebrafish, and mammalian cells.

This detailed volume focuses on best practices and conditions for maintaining the most commonly used salamander species in the laboratory. Salamanders in Regeneration Research: Methods and Protocols guides readers through experimental manipulations in vivo and in vitro, respectively. With methods on targeting a wide variety of structures, ranging from the limb to the heart and to the brain, and methods for studying genetically modified organisms and tools for mining in the genomic databases. Written in the highly successful Methods in Molecular Biology series format, chapters include introduction 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. Authoritative and up-to-date, Salamanders in Regeneration Research: Methods and Protocols provides a comprehensive collection of methods chapters.

This book presents regenerative strategies for the treatment of knee joint disabilities. The book is composed of four main sections totaling 19 chapters which review the current knowledge on the clinical management and preclinical regenerative strategies. It examines the role of different natural-based biomaterials as scaffolds and implants for addressing different tissue lesions in the knee joint. Section one provides an updated and comprehensive discussion on articular cartilage tissue regeneration. Section two focuses on the important contributions for bone and osteochondral tissue engineering. Section three overview the recent advances on meniscus repair/regeneration strategies. Finally, section four further discusses the current strategies for treatment of ligament lesions. Each chapter is prepared by world know expert on their fields, so we do firmly believe that the proposed book will be a reference in the area of biomaterials for regenerative medicine.

This book describes modern biophysical techniques that enable us to understand and examine dynamic processes of infection at the molecular level. Cutting-edge research articles, laboratory protocols, case studies and up-to-date reviews cover topics such as single-molecule observation of DNA replication repair pathways in E. coli; evolution of drug resistance in bacteria; restriction enzymes as barriers to horizontal gene transfer in Staphylococcus aureus; infectious and bacterial pathogen biofilms; killing infectious pathogens through DNA damage; bacterial surfaces in host-pathogen interactions; bacterial gene regulation by riboswitches; transcription regulation in enterobacterial pathogens; the bacterial flagellar motor; initial surface colonization by bacteria; Salmonella Typhi host restrictions; as well as monitoring proton motive force in bacteria; microbial pathogens using digital holography; mathematical modelling of microbial pathogen motility; neutron reflectivity in studying bacterial membranes; force spectroscopy in studying infection and 4D multi-photon imaging to investigate immune responses. The focus is on the development and application of complex techniques and protocols at the interface of life sciences and physics, which increase the physiological relevance of biophysical investigations.

This volume brings together the skills and protocols of numerous laboratories that are at the heart of investigation into the biology of Tfh cells in both mice and humans. As a volume in the highly successful Methods in Molecular Biology series, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Concise and easy-to-use, T follicular Helper Cells: Methods and Protocols provides scientist with techniques and protocols that have facilitated breakthroughs in Tfh biology and to present them in a way that will enable both new and experienced researchers to continue to move this exciting field forward.

The rapid expansion of the area of free radical biology in the last 25 years has occurred within a framework of assumptions and preconceived notions that has at times directed the course of this movement. The most dominant of these notions has been the view that free radical production is without exception a bad thing, and that the more efficient our elimination of these toxic substances, the better off we will be. The very important observation by Bernard Babior and colleagues in 1973 that activated phagocytes produce superoxide in order to kill micro organisms, served to illustrate that constructive roles are possible for free radicals. For many in the field, however, this merely underscored the deadly nature of oxygen-derived radicals, both from the microbe's point of view and from the host's as well. (Phagocyte-produced superoxide is responsible in part for the tissue injury manifested as inflammation. See Harris and Granger, Chapter 5, and Leff, Hybertson and Repine, Chapter 6.)
Mother Nature, however, has a penchant for being able to make a silk purse from a sow's ear. If one is dealt a bad hand, one must simply make the best of it. After two decades of focusing on the destructive side of free radicals, the last few years have begun to reveal a new and finer perspective on free radical metabolism - a role in regulation of cellular function (see Schulze-Osthoff and Baeuerle, Chapter 2). Evidence from a number of sources suggests that an increase in the oxidative status of cell encourages that cell to grow and divide. Increasing the expression of mangnese superoxide dismutase can suppress the malignant phenotype of melanon cells (see Oberley and Oberley, Chapter 3). Oxidative stress beyond a certain poitosis (from the Greek, literally "to fall apart"). Is this suicide response an evolutionary fail-safe device to curtail tumorogenesis? Does oxidative stress-induced apoptosis account for the loss of immune cells in AIDS (see Flores and McCor Chapter 4)?
This volume attempts to present the spectrum of roles, both good and bad played by active oxygen species as understood at this point in the evolution of this field of free radical biology.

Mesenchymal stem cell-derived exosomes are at the forefront of research in two of the most high profile and funded scientific areas - cardiovascular research and stem cells. Mesenchymal Stem Cell Derived Exosomes provides insight into the biofunction and molecular mechanisms, practical tools for research, and a look toward the clinical applications of this exciting phenomenon which is emerging as an effective diagnostic. Primarily focused on the cardiovascular applications where there have been the greatest advancements toward the clinic, this is the first compendium for clinical and biomedical researchers who are interested in integrating MSC-derived exosomes as a diagnostic and therapeutic tool.

Anaerobiosis and Stemness: An evolutionary paradigm provides a context for understanding the many complexities and evolutionary features of stem cells and the clinical implications of anaerobiosis stem cells. Combining theoretical and experimental knowledge, the authors provide a broad understanding of how the absence or low concentration of oxygen can play an influential role in the maintenance and self-renewal of stem cells and stem cell differentiation. This understanding has clinical implications for the fields of regenerative medicine, cancer biology and transplantation, as well as cell engineering and cell therapy. Anaerobiosis and Stemness is an important resource for stem cell and developmental biologists alike, as well as oncologists, cancer biologists, and researchers using stem cells for regeneration.

With a focus on food safety, this book highlights the importance of microbes in sustainable agriculture. Plants, sessile organisms that are considered as primary producers in the ecosystem and communicate with above- and below-ground communities that consist of microbes, insects, and other vertebrate and invertebrate animals, are subjected to various kinds of stress. Broadly speaking, these can be subdivided into abiotic and biotic stresses. Plants have evolved to develop elaborate mechanisms for coping with and adapting to the environmental stresses. Among other stresses, habitat-imposed biotic stress is one serious condition causing major problems for crop productivity. Most plants employ plant-growth-promoting microorganisms (PGPMs) to combat and protect themselves from stresses and also for better growth. PGPMs are bacteria associated with plant roots and they augment plant productivity and immunity. They are also defined as root-colonizing bacteria that have beneficial effects on plant growth and development. Remarkably, PGPMs including mycorrhizae, rhizobia, and rhizobacteria (Acinetobacter, Agrobacterium, Arthrobacter, Azospirillum, Bacillus, Bradyrhizobium, Frankia, Pseudomonas, Rhizobium, Serratia, Thiobacillus) form associations with plant roots and can promote plant growth by increasing plants' access to soil minerals and protecting them against pathogens. To combat the pathogens causing different diseases and other biotic stresses, PGPMs produce a higher level of resistance in addition to plants' indigenous immune systems in the form of induced systemic resistance (ISR). The ISR elicited by PGPMs has suppressed plant diseases caused by a range of pathogens in both the greenhouse and field. As such, the role of these microbes can no longer be ignored for sustainable agriculture. Today, PGPMs are also utilized in the form of bio-fertilizers to increase plant productivity. However, the use of PGPMs requires a precise understanding of the interactions between plants and microbes, between microbes and microbiota, and how biotic factors influence these relationships. Consequently, continued research is needed to develop new approaches to boost the efficiency of PGPMs and to understand the ecological, genetic and biochemical relationships in their habitat. The book focuses on recent research concerning interactions between PGPMs and plants under biotic stress. It addresses key concerns such as - 1. The response of benign microbes that benefit plants under biotic stress 2. The physiological changes incurred in plants under harsh conditions 3. The role of microbial determinants in promoting plant growth under biotic stress The book focuses on a range of aspects related to PGPMs such as their mode of action, priming of plant defence and plant growth in disease challenged crops, multifunctional bio-fertilizers, PGPM-mediated disease suppression, and the effect of PGPMs on secondary metabolites etc. The book will be a valuable asset to researchers and professionals working in the area of microbial-mediated support of plants under biotic stress.