This work describes the current knowledge of biochemical mechanisms regulating initiation of DNA replication in Escherichia coli, which focuses on the control of activity of the DnaA protein. Examples of direct linkages between DNA replication and other cellular processes are provided. In addition, similarities of the mechanisms of regulation of DNA replication operating in prokaryotic and eukaryotic cells are identified, and implications for understanding more complex processes, like carcinogenesis are suggested.Studies of recent years provided evidence that regulation of DNA replication in bacteria is more complex than previously anticipated. Multiple layers of control seem to ensure coordination of this process with the increase of cellular mass and the division cycle. Metabolic processes and membrane composition may serve as points where integration of genome replication with growth conditions occurs. It is also likely that coupling of DNA synthesis with cellular metabolism may involve interactions of replication proteins with other macromolecular complexes, responsible for various cellular processes. Thus, the exact set of factors participating in triggering the replication initiation may differ depending on growth conditions. Therefore, understanding the regulation of DNA duplication requires placing this process in the context of the current knowledge on bacterial metabolism, as well as cellular and chromosomal structure. Moreover, in both Escherichia coli and eukaryotic cells, replication initiator proteins were shown to play other roles in addition to driving the assembly of replication complexes, which constitutes another, yet not sufficiently understood, layer of coordinating DNA replication with the cell cycle.

This is comprehensive overview of a vital area of scientific enquiry, which covers a broad spectrum of issues. With contributions from some of the key researchers in the field, Adult Stem Cells: Biology and Methods of Analysis offers readers a historical perspective as well as unique insights into cutting-edge thoughts. The volume contextualizes the recent discovery of stem/progenitor cell populations resident in many adult tissues and organs. It confronts the complexities scientists face in trying to validate these cells, while it also describes and critically evaluates the methods currently used to assess stem cell self-renewal. The chapters also seek to distinguish this process from other aspects of cell survival, such as the regulation of life span, senescence, and immortalization at a molecular level. The monograph begins with a section that examine the basic biology of adult stem cells, including chapters on the emerging role of microRNAs in regulating their fate and the molecular mechanisms that govern their self-renewal, the book moves on to analyze the varying methodologies employed in characterizing these elusive elements of our genetic make-up. The second section details in-vivo lineage tracing of tissue-specific stem cells, explores the neural stem cell paradigm, and considers the function of ABC transporters and aldehyde dehydrogenase in adult stem-cell biology. The final section shifts the focus to the life-span regulation and immortalization and features a chapter on the cancer stem cell paradigm. This is an authoritative volume on one of the frontiers of genetic research, and will serve as a valuable resource, not just for established scientists but also for those now entering the field of stem cell biology.

Timing, racing, combating, struggling and targeting are some actions through which cellular fate could be reflected and evaluated. Interaction between cell territory and environment occur during pre-embryonic, fetal development, and post-natal periods. What the researchers observe as the outcome of telomeres behavior is only the peak of an ice mountain within a stormy ocean. Cellular life depends on programmed behavior of telomeres, capable to surprise the cells. Telomeres provide an introduction to the history of our cells which govern the quality of life and status of health. Telomeres as the cooperative territory are capable of stabilizing the chromosomal territory. The status of telomeres reflects the key information, announcing the real age of individuals, and may be a valuable marker for prognosis and predicting cancer. Telomere territory is characterized with a multi-disciplinary manner. Therefore, this book is aimed to offer a wide range of chapters, hoping to be useful for diverse audiences, including hematologists-oncologists, radiotherapists, surgeons, cancer researchers, and all the sectors who affect the macro- and micro- environmental domains. Finally, telomeres are sensitive, cooperative, and trustable targets. It is worth to state that 'telomeres are messengers of NATURE', let's to know them as they are.

The mouse is a perfect model organism to study mammalian, and thus indirectly also human, embryology. Most scientific achievements that have had an important impact on the understanding of basic mechanisms governing embryo development in humans, originated from mouse embryology. Stem cell research, which now offers the promise of regenerative medicine, began with the isolation and culture of mouse embryonic stem cells by Martin Evans (who received the Nobel Prize in medicine in 2007 for this achievement) and Matthew Kaufman. This book provides an overview of mouse development, spanning from oocytes before fertilization to the state-of-the-art description of embryonic and adult stem cells. The chapters, written by the leading specialists in the field, deal with the most recent discoveries in this extremely fast-developing area of research.

Genetic Regulatory Networks (GRNs) in biological organisms are primary engines for cells to enact their engagements with environments, via incessant, continually active coupling. In differentiated multicellular organisms, tremendous complexity has arisen in the course of evolution of life on earth. Engineering and science have so far achieved no working system that can compare with this complexity, depth and scope of organization. Abstracting the dynamics of genetic regulatory control to a computational framework in which artificial GRNs in artificial simulated cells differentiate while connected in a changing topology, it is possible to apply Darwinian evolution in silico to study the capacity of such developmental/differentiated GRNs to evolve. In this volume an evolutionary GRN paradigm is investigated for its evolvability and robustness in models of biological clocks, in simple differentiated multicellularity, and in evolving artificial developing 'organisms' which grow and express an ontogeny starting from a single cell interacting with its environment, eventually including a changing local neighbourhood of other cells. These methods may help us understand the genesis, organization, adaptive plasticity, and evolvability of differentiated biological systems, and may also provide a paradigm for transferring these principles of biology's success to computational and engineering challenges at a scale not previously conceivable.

Therapeutic applications within regenerative biomedicine has gained tremendous interest from a growing, multidisciplinary community of investigators in recent years, driven by the hope of finding cures for several diseases. Regenerative Medicine and Cell Therapy discusses cutting-edge science in the field of regenerative biomedicine and its therapeutic applications to various medical disorders. The chapters are written by renowned scientists in the specific fields. This will be a useful book for basic and clinical scientists, especially young investigators and stem cell biology students who are newly entering the world of stem cells research. The editors' goal is that the new knowledge and research outlined in this book will help contribute to new therapies for a wide variety of diseases that presently afflict humanity.

Regulating virtually all biological processes, the genome’s 2,654 newly discovered variants of mature microRNAs – short ribonucleic acid molecules found in eukaryotic cells – hold a key role in the body’s toolkit of regenerative and reparative capacities. Identifying how to activate and deliver these specialist molecules may aid in the repair and regeneration of major tissue and organ damage in future therapies. In MicroRNA and Regenerative Medicine, Second Edition, over 50 leading experts address foundational and emerging topics in the field. Concisely summarizing and evaluating key findings from new research and their translational application, contributors examine current and future significance of clinical research in the miRNA area. Coverage encompasses all major aspects of fundamental stem cell and developmental biology, including the uses of miRNA in cell and tissue plasticity, developmental biology, tissue repair, and regeneration. In particular, contributors provide focused coverage of methodologies for regenerative intervention and tissue engineering. Topics new to this edition include proteomic changes during tissue repair and regeneration, horizontal transfer of miRNAs in tissue regeneration, tissue stemness, peripheral nerve regeneration, miRNA as biomarkers, microRNA in pregnancy and embryo development, exogenous and diet derived microRNA in tissue development, ocular microRNA, mitochondrial microRNA, sensory hair cell death and regeneration, and microRNA in senescence.

In "Animal Models for Stem Cell Therapy: Methods and Protocols, "expert researchers in the field detail disease models of hepatic, cardiovascular, neurological diseases, connective and contractile tissue. Chapters focus on a wide range of diseases and application of different kinds of stem cells and reprogrammed tissue cells (iPS).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 key tips on troubleshooting and avoiding known pitfalls.

Authoritative and practical, "Animal Models for Stem Cell Therapy: Methods and Protocols, "covers interest of basic scientists and clinicians to assess the biological as well as the therapeutic potential of stem cell therapy."

From DNA sequences stored on computer databases to archived forensic samples and biomedical records, bioinformation comes in many forms. Its unique provenance the fact that it is 'mined' from the very fabric of the human body makes it a mercurial resource; one that no one seemingly owns, but in which many have deeply vested interests. Who has the right to exploit and benefit from bioinformation? The individual or community from whom it was derived? The scientists and technicians who make its extraction both possible and meaningful or the commercial and political interests which fund this work? Who is excluded or even at risk from its commercialisation? And what threats and opportunities might the generation of 'Big Bioinformational Data' raise? In this groundbreaking book, authors Bronwyn Parry and Beth Greenhough explore the complex economic, social and political questions arising from the creation and use of bioinformation. Drawing on a range of highly topical cases, including the commercialization of human sequence data; the forensic use of retained bioinformation; biobanking and genealogical research, they show how demand for this resource has grown significantly driving a burgeoning but often highly controversial global economy in bioinformation. But, they argue, change is afoot as new models emerge that challenge the ethos of privatisation by creating instead a dynamic open source 'bioinformational commons' available for all future generations.

When Richard Goldschmidt emigrated to the United States in 1936, he had influenced a whole generation of young biologists, and had stimulated their research by his revolutionary ideas. Stern (1967, see p. 21) called him: 'Contributor of permanent parts, some very large; preceptor and critic of his era; designer of frameworks for the future'. In 1958 Goldschmidt's obituary was prefaced by the following statement: 'Der nachstehende Nekrolog erscheint gleichzeitig in Science und Ex- perientia, damit das universale Heimatrecht Richard Goldschmidts zum Ausdruck bringend. Die Leser von Experientia erinnern sich dankbar der verschiedenen genetischen Aufsiitze dieses immer anregenden Geistes, dem unsere Wissenschaft grosse Impulse verdankt.' (Translation: The following obituary appears simultaneously in Science and in Experientia, a symbol of Richard Goldschmidt's right to be called a world citizen. Readers of Experientia will recall with appreciation several of the papers of this highly stimulating author to whom our science owes a great deal. (Experientia 14, 307, 1958). In commemoration of the 20th anniversary of Richard Goldschmidt's death (April 24, 1958) and the 100th anniversary of his birth (April 12, 1878) Experientia presents a contemporary evaluation of several of Goldschmidt's major scientific theories. We believe that some of these theories were far ahead of his time and that the controversies which they aroused are of considerable didactic interest to biologists today. Further- more, they represent an important chapter in the history of biology.

The post-genomic era has brought new challenges and opportunities in all fields of the biology. In this context, several genome engineering technologies have emerged that will help deciphering genes function by as well as improve gene therapy strategies. Genomic modifications such as knock-in, knock-out, knock-down, sequence replacement or modification can today be routinely performed. However, in front of this large palette of methodologies scientists may experience difficulties to gather useful information's scattered within the literature. This book aims to present the state of this field from basic mechanisms of site-directed modifications to their applications in a wide range of organisms such as bacteria, yeast, plants, insects, mammals. It will discuss the problems encountered when using the random integration strategy and present the recent advances made in targeted genome modification. Technologies based on Zinc Finger nucleases, Meganucleases, TALEN, CRE and FLP recombinase, C31 integrase, transposases and resolvases are fully detailed with their strengths and weaknesses. All these information's will help students and experienced researchers to understand and choose the best technology for their own purposes.

The existence of 'cancer stem cells' (CSCs) has been a topic of heated debate for the last few years within the field of cancer biology. Their continuous characterization in a variety of solid tumors has lead to an abundance of evidence supporting their existence. CSCs are believed to be responsible for resistance against conventional treatment regimes of chemotherapy and radiation, ultimately, leading to metastasis and patient demise. To help aid clinicians, pharmaceutical companies and academic labs investigating how to better kill these highly aggressive cells we have summarized the DNA repair mechanism(s) and their role in the maintenance and regulation of both normal and cancer stem cells. Our book represents a comprehensive investigation into the highly effective DNA repair mechanisms of CSCs and what we need to understand in order to develop more advanced therapies to eradicate them from patients. Currently, there are no other published works entirely on DNA repair and Cancer Stem Cells. In addition, our book provides a comprehensive overview of CSC isolation and characterization from a variety of solid tumor types.

Updating and building upon previous editions, "Hematopoietic Stem Cell Protocols, Third Edition" provides up-to-date protocols from leading stem cell researchers. This in-depth volume presents a clear view of the landscape of assays available to the stem cell researcher working in the growing hematopoietic stem cell (HSC) field. A robust and active field, it is supported by an abundance of innovative mouse models and molecular tools for analysis of phenotypes and functions in mouse and human cells. Understanding more about hematopoietic stem cell biology is integral if these versatile cells are to be applied effectively to treat and cure a wide range of blood diseases.An introductory chapter puts the major contributions of the book into the proper perspective. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls.

Essential for the laboratory-based researcher, "Hematopoietic Stem Cell Protocols, Third Edition" is a much needed technical resource in the critically important field of hematopoietic stem cell investigation."

"Directed Evolution Library Creation: Methods and Protocols, Second Edition "presents user-friendly protocols for both proven strategies and cutting-edge approaches for the creation of mutant gene libraries for directed evolution. As well as experimental methods, information on current computational approaches is provided in a user-friendly format that will allow researchers to make informed choices without needing to comprehend the full technical details of each algorithm. Directed evolution has become a fundamental approach for engineering proteins to enhance activity and explore structure-function relationships, and has supported the rapid development of the field of synthetic biology over the last decade. Divided into three convenient sections, topics include point mutagenesis strategies, recombinatorial methods wherein genetic diversity is sourced from multiple parental genes that are combined via either homology-dependent or -independent techniques and a variety of computational methods to guide the design and analysis of mutant libraries. Written in the 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 protocols and notes on troubleshooting and avoiding known pitfalls.

Authoritative and easily accessible, "Directed Evolution Library Creation: Methods and Protocols, Second Edition "will serve as a reliable manual for both novice and experienced protein engineers and synthetic biologists and will enable further technical innovation and the exploitation of directed evolution for a deeper understanding of protein design and function.

This book is written by leading researchers in the fields about the intersection of genetics and metabolomics which can lead to more comprehensive studies of inborn variation of metabolism.

JAK tyrosine kinases and STAT transcription factors constitute a signaling pathway, which is activated by cytokines. By activating gene transcription it regulates essential biological responses to environmental cues. The Jak-Stat pathway is involved in the regulation of cell development, differentiation, proliferation and apoptosis. Improper function may contribute to hematopoietic malignancies and cancer. This book provides comprehensive insights into the latest basic and clinical developments in the field. The first part reviews recent findings and new technologies pertaining to basics of Jak-Stat function. The second part describes the evolution of Jak-Stat signaling and the role of the pathway in invertebrate organisms. The third part focuses on Jak-Stat signaling in hematopoietic cells under both physiological and pathophysiological conditions. Finally, chapters in the fourth section describe the relationship of Jak-Stat signaling to various states of disease, particularly infection, leukemias and solid cancers. The book is intended for all scientists in molecular biology, biochemistry and cell biology dealing with biomedical issues.

Trypanosomes are unicellular protozoa of ancient evolutionary origin that are responsible for several tropical diseases, such as African sleeping sickness. Over the last few decades, research in trypanosome biology has revealed many unique and fascinating features, many of which have helped to establish new paradigms in other biological systems. This applies in particular to studies in gene expression and regulation, which benefit enormously from the trypanosome genome projects and from the new genome-wide approaches recently introduced in trypanosome research. This volume covers the most important aspects of biosynthesis, processing, and functions of RNA in trypanosomes, ranging from transcription to RNA editing, mRNA splicing/translation/turnover, processing of transfer and ribosomal RNA, RNA interference, and current transcriptome-wide analyses. Recent progress in RNA-focused research in trypanosomatids promises to yield novel insights into trypanosome-specific features, as well as to reveal in the process new potential therapeutic strategies for combating these parasitic diseases.

"Biomimetics and Stem Cells: Methods and Protocols" collects a series of approaches to demonstrate the role and value of biomimetics for the better understanding of stem cell behavior and the acceleration of their application in regenerative medicine. Recent advances in tissue engineering are enabling scientists to instruct stem cells toward differentiating into the right phenotypes, in the right place and at the right time. Given these advances, biomimetic environments are being designed to recapitulate, in vitro, the combinations of factors known to guide tissue development and regeneration in vivo and thereby help unlock the full potential of the stem 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.Practical and essential, "Biomimetics and Stem Cells: Methods and Protocols" focuses on the use of biomimetic systems for stem cells in order to aid in moving this vital field of study forward."

This book describes how genomics has revolutionized our scientific understanding of agriculturally important plant-associated bacteria. Each chapter focuses on the genomics of particular bacteria: the first described plant pathogen, "Erwinia amylovora"; phytoplasmas lacking cell walls; fastidious, phloem-restricted liberibacters; "Pseudomonas syringae," which is a genetically tractable model system; "Xanthomonas citri," which causes a disease that can devastate citrus crops and "Pseudomonas fluorescens," which can protect plants from diseases.

Topics considered in this volume include the importance of horizontal gene transfer in originating new bacterial strains and species and advances in transcriptomics that allow us to describe the complex regulatory networks critical to plant-microbe interactions. The availability of the "Xanthomonas oryzae" genome has led to new technologies in genome editing, which will revolutionize approaches to genetic engineering, even in eukaryotes. The contributions show how genomics has greatly accelerated progress toward understanding the biology of these bacteria and how that understanding can be translated into novel crop protection methods.

Innate DNA and RNA Recognition: Method and Protocols presents validated experimental strategies to dissect nucleic acid sensing in-vitro and in-vivo sources. 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 practical, Innate DNA and RNA Recognition: Method and Protocols provides a resource for immunologists, molecular biologists, virologists, microbiologists, and researchers studying how the innate immune system handles nucleic acids from endogenous or foreign sources.

Advances in Stem Cell Research discusses recent advances in stem cell science, including therapeutic applications. This volume covers such topics as biomanufacturing iPS cells for therapeutic applications, techniques for controlling stem cell fate decisions, as well as current basic research in such areas as germ line stem cells, genomics and proteomics in stem cell research. It is a useful book for biology and clinical scientists, especially young investigators and stem cell biology students who are newly entering the world of stem cells research. The editors hope that the new knowledge and research outlined in this book will help contribute to new therapies for a wide variety of diseases that presently afflict humanity.

Stem cells have the ability to differentiate into all types of cells within the body, thus have great therapeutic potential for regenerative medicine to treat complicated disorders, like Parkinson s disease and spinal cord injury. There will also be many applications in drug development. However, several roadblocks, such as safety issues and low efficiency of pluripotent stem cell (PSC) line derivation need to be resolved before their clinical application. This thesis focuses on these two areas, so as to find methods to overcome the limitation. It covers deriving embryonic stem cells (ESCs) from several different species and reports an efficient system to generate induced pluripotent stem cells (iPSCs), and the first iPSC mice in the world. The results in this thesis confirm that somatic cells can be fully reprogrammed with the four Yamanaka factors. In addition, we have found that the Dlk1-Dio3 region can be a potential molecular marker to distinguish the fully reprogrammed iPSCs from partially reprogrammed ones. All of these results will help improve the safety of PSCs in the clinical applications and increase the current low induction efficiency of their production."

This text is a comprehensive look at the current knowledge on stem cell application for vision loss, showcasing different types of stem cells (adult, embryonic, iPSCs) for diseases of the front and the back of the eye. It also highlights data obtained in various models from fish to human, as well as from the bionic eye project for vision regeneration. This volume in the Stem Cell Biology and Regenerative Medicine series is essential reading for stem cell biologists, ophthalmologists, advanced and graduate students, in addition to academics and medical staff who work in these disciplines.

There is hardly an area of research developing so quickly and raising so many promises as stem cell research. Adult, embryonic and recently available induced pluripotent stem cells not only foster our understanding of differentiation of endo-, ecto- and mesodermal lineages to all organs of the body, but foremost nourish the hope that cells grown in culture can be used for regeneration of diseased organs such as the heart damaged by myocardial infarction. This book focuses on perspectives of stem cells for regenerative therapy of cardiovascular diseases. Based on the EC consortium INELPY, it reviews the field and disseminates major outcomes of this project. Thus it introduces the reader to this fascinating area of research and incorporates very recent findings interesting to the expert, spanning the field from bench to bedside. The compilation of contributions is unique as there is yet no similar comprehensive overview combining stem cell research with preclinical and clinical evaluation as well as engineering of tissue patches for transplantation. As such it will be an invaluable source of information for all researchers in the stem cell and tissue regeneration field including bioengineers as well as for all clinicians interested in regenerative therapies, especially for ischemic cardiomyopathies.

This book exemplifies experience across the globe in banking of cord blood, mesenchymal, embryonic and induced pluripotent stem cells for clinical use from the United States, Canada, the European Union, Switzerland and Japan to Iran, India and Serbia. The concerns are similar regardless of stem cell type or origin. Implementing core values and common standards depend often on specific circumstances of political and economic setting, which makes flexibility as important as systematic planning. Banking of stem cells is not just building a repository and storing samples. The planning, design, construction and maintenance involve multiple skilled professionals. Stem cell banks are points where technology and medicine converge with ethics, laws and regulations. If properly designed and organized, their utilization will have a broad impact not only on the scientific community and medical professionals but also on the general public.