Synthetic mRNA is an attractive tool for mammalian cell reprogramming that can be used in basic research, as well as in clinical applications. Present mRNA in vitro synthesis is a rather simple procedure, which delivers a high yield of quality product. Various modifications may be introduced into the mRNA by changing the sequence of the DNA template, by modifying the reaction of transcription, or by post-transcriptional modification. mRNA, as a transfection agent, has several advantages over DNA, as mRNA expression is not dependent on nuclear entry and occurs directly in the cytosol. Synthetic Messenger RNA and Cell Metabolism Modulation: Methods and Protocols covers the typical main methods, such as mRNA synthesis, modifications, and delivery. Examples of cell reprogramming and analysis in the fields of immunotherapy and stem cell research are also included. Written in the successful Methods in Molecular Biology (TM) 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, Synthetic Messenger RNA and Cell Metabolism Modulation: Methods and Protocols will be of interest to researchers, clinicians, and biotech companies interested in mRNA-mediated cell reprogramming.

Heart disease is the leading cause of death in developed countries. Recent experimental advances featuring cellular, molecular, and genetic tools and technologies offer the potential for new therapeutic strategies directed toward remediation of inherited and acquired heart diseases. Whether these recent basic science advances will ultimately translate to clinical efficacy for patients with heart disease is unknown and is important to ascertain. Cardiac Cell and Gene Transfer: Principles, Protocols, and Applications is designed to provide the reader with up-to-date coverage of a myriad of specific methodo- gies and protocols for gene and cell transfer to the myocardium. Each chapter features a "Notes" section that provides useful "how to" problem-solving insights that are often left unstated in standard published protocols. Cardiac Cell and Gene Transfer: Principles, Protocols, and Appli- tions addresses principles and applications of cell and gene transfer to the heart, including protocols for vector production and purification. Detailed step-by-step methods and applications for first/second-generation adenoviral vectors, adeno-associated vectors, gutted adenoviral vectors, and lentiviral vectors are included. Additionally, detailed methods for cardiac cell grafting and transplantation are provided, and these chapters highlight the prospects of cell-based therapies for cardiac repair. The book also covers specific in vivo techniques for cardiac gene transfer, and specifies subsequent cellular and organ-level physiological assessment techniques and protocols. Accordingly, this book is designed for basic science and clinical researchers in the academic, pharmaceutical, and biotechnology sectors of the cardiovascular community.

All physicians practicing medicine encounter patients suffering from cardiovascular disease. This book has been outlined in such a way that vascular surgeons, general internists, neurologists and cardiologists should be able to use it. The book covers the complete scope of cardiac diseases in addition to chapters on hypertension and atherosclerosis. In many patients there is a family history of cerebrovascular accidents, myocardial infarction or peripheral arterial disease. Also in patients reporting collaps, palpitations and arrhythmias the family is crucial and can provide clues to a genetic cause of the disease. This book is published to guide physicians in the process of determining whether a genetic component is likely to be present. Furthermore, information is provided what the possibilities and limitations of DNA diagnostic techniques are. Finally, the importance of newly identified categories of potential patients, i. e. gene carriers without symptoms or any inducible sign of disease, is highlighted. For some patients a genetic diagnosis is essential to determine appropriate therapy and for counseling? In some other diseases DNA diagnostic tools are available but the relevant for the patients may be less clear. In other families the search for a disease causing gene is ongoing and the possibilities to find genes and to unravel the pathophysiology of the disease is limited by the lack of patients. To give insight into the current state of genetic diagnostics, the authors have classified the cardiovascular diseases.

This book provides a conceptual and computational framework to study how the nervous system exploits the anatomical properties of limbs to produce mechanical function. The study of the neural control of limbs has historically emphasized the use of optimization to find solutions to the muscle redundancy problem. That is, how does the nervous system select a specific muscle coordination pattern when the many muscles of a limb allow for multiple solutions? I revisit this problem from the emerging perspective of neuromechanics that emphasizes finding and implementing families of feasible solutions, instead of a single and unique optimal solution. Those families of feasible solutions emerge naturally from the interactions among the feasible neural commands, anatomy of the limb, and constraints of the task. Such alternative perspective to the neural control of limb function is not only biologically plausible, but sheds light on the most central tenets and debates in the fields of neural control, robotics, rehabilitation, and brain-body co-evolutionary adaptations. This perspective developed from courses I taught to engineers and life scientists at Cornell University and the University of Southern California, and is made possible by combining fundamental concepts from mechanics, anatomy, mathematics, robotics and neuroscience with advances in the field of computational geometry. Fundamentals of Neuromechanics is intended for neuroscientists, roboticists, engineers, physicians, evolutionary biologists, athletes, and physical and occupational therapists seeking to advance their understanding of neuromechanics. Therefore, the tone is decidedly pedagogical, engaging, integrative, and practical to make it accessible to people coming from a broad spectrum of disciplines. I attempt to tread the line between making the mathematical exposition accessible to life scientists, and convey the wonder and complexity of neuroscience to engineers and computational scientists. While no one approach can hope to definitively resolve the important questions in these related fields, I hope to provide you with the fundamental background and tools to allow you to contribute to the emerging field of neuromechanics.

Based on an intensive qualitative study of a diverse group of 51 older widowers, this unique book sets widowhood within the context of life experience and identifies characteristics and patterns of behaviour that contribute to widowers' success, or lack of it, in adjusting satisfactorily to their circumstances. The authors shed light on widowers' specific needs and on the services needed to help widowers develop greater self-reliance. Among the topics discussed are models of resilience, marriage and illness of the spouse, caregiving and communication, death of the wife, grief and adjustment, living alone and remarriage, life values carried forward, adult children and other social support, and cohorts and the future. The authors conclude with a consideration of trends that may influence the next generation's experience of widowhood. This excellent volume offers expert guidance on the needs and care of the nearly invisible population of older widowers.

RNA technologies are the driving forces of modern medicine and biotechnology. They combine the fields of biochemistry, chemistry, molecular biology, cell biology, physics, nanotechnology and bioinformatics. The combination of these topics is set to revolutionize the medicine of tomorrow. After more than 15 years of extensive research in the field of RNA technologies, the first therapeutics are ready to reach the first patients. Thus we are witnessing the birth of a very exciting time in the development of molecular medicine, which will be based on the methods of RNA technologies. This volume is the first of a series. It covers various aspects of RNA interference and microRNAs, although antisense RNA applications, hammerhead ribozyme structure and function as well as non-coding RNAs are also discussed. The authors are internationally highly respected experts in the field of RNA technologies.

This detailed volume will focus on the phenomenon of RNA interference by providing comprehensive coverage of various techniques for in vivo micro/siRNA imaging including the design and synthesis of specific imaging agents and tools, the development of imaging methodologies, and their interpretation. An essential element in the development and optimization of these therapies is the ability to measure the bioavailability and functionality of the RNA/oligonucleotide molecule after administration into the body. Noninvasive imaging provides the necessary set of tools to accomplish this in authentic physiologic environments and across time. 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. Authoritative and practical, RNA Imaging: Methods and Protocols serves physicians, scientists, and graduate students who are either new to the field of RNA-based imaging and its associated therapeutic applications or who wish to be apprised of recent advances in the state of the art.

International Review of Cytology presents current advances and comprehensive reviews in cell biology--both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.
Key Features
* Authored by some of the foremost scientists in the field
* Provides up-to-date information and directions for future research
* Valuable reference material for advanced undergraduates, graduate students and professional scientists

Laser microdissection techniques have revolutionized the ability of researchers in general, and pathologists in particular, to carry out molecular analysis on specific types of normal and diseased cells and to fully utilize the power of current molecular technologies including PCR, microarrays, and proteomics. In second edition of Laser Capture Microdissection: Methods and Protocols, experts in the field provide the reader with practical advice on how to carry out tissue-based laser microdissection successfully in their own laboratory using the different laser microdissection systems that are available and to apply a wide range of molecular technologies. The individual chapters encompass detailed descriptions of the individual laser based micro-dissection systems. The downstream applications of the laser microdissected tissue described in the book include PCR in its many different forms as well as gene expression analysis including application to microarrays and proteomics. Written in the highly successful Methods in Molecular Biology (TM) 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, Laser Capture Microdissection: Methods and Protocols, Second Edition is an ideal resource for researchers striving to move forward our understanding of normal physiology and pathology.

International Review of Cytology presents current advances and comprehensive reviews in cell biology both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.
Key Features
* Authored by some of the foremost scientists in the field
* Provides up-to-date information and directions for future research
* Valuable reference material for advanced undergraduates, graduate students and professional scientists

The endothelins are a remarkable family of signaling peptides: molecular biology predicted the existence of their receptors and synthetic enzymes prior to both the identification of the encoded proteins and the synthesis of antagonists and inhibitors for use as pharmacological tools. Although considerable advances have been made, culminating in the design of endothelin antagonists with the- peutic potential in cardiovascular disease, much remains to be discovered. Tantalizingly, new research frontiers are emerging. To support further progress, Peptide Research Protocols: Endothelin encompasses experimental protocols that interrogate all facets of an endogenous mammalian peptide s- tem, from peptide and receptor expression through synthetic pathway to peptide function and potential role in human disease. Chapters describe the use of molecular techniques to quantify the expression of mRNA for both endothelin receptors and the endothelin-converting enzymes. Peptides, precursors, receptors, and synthetic enzymes may be localized and quantified in plasma, culture supernatants, tissue homogenates, and tissue s- tions using antibodies, while additional information on receptor characterization may be obtained using radioligand binding techniques. Several protocols cover in vitro assays that determine the function of the endothelin peptides in isolated preparations, that characterize new endothelin receptor ligands, or provide inf- mation on the tissue-specific processing of endothelin precursor peptides.

From the 40th annual conference of the International Society on Oxygen Transport to Tissue (ISOTT), held in Bruges, Belgium in August 2012, this volume covers aspects of clinical applications, muscle oxygenation, cancer, measurement technologies, oxygen transport modelling and Near-Infrared Spectroscopy (NIRS), cell metabolism and brain oxygenation. Each topic was presented by one or two invited speakers, and a series of contributed talks.

The dynamics of body metabolism are changed in the disease process and interact with physical activity. The alteration of metabolism and its consequences raise the need for simple and reliable methods for assessment of body composition. The chapters aim to investigate various interacting components converging on metabolic changes in lung and muscle tissues taking into consideration the drug effects. The effects of exercise and nutritional status are dealt with at a great extent.

International Review of Cytology presents current advances and comprehensive reviews in cell biology--both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.

Infertility and assisted reproductive technologies in India lie at the confluence of multiple cultural conceptions. These 'conceptions' are key to understanding the burgeoning spread of assisted reproductive technologies and the social implications of infertility and childlessness in India. This longitudinal study is situated in a number of diverse locales which, when taken together, unravel the complex nature of infertility and assisted conception in contemporary India.

This volume contains 29 engrossing chapters contributed by worldwide, leading research groups in the field of chemical biology. Topics include pre-biology; the establishment of the genetic code; isomerization of RNA; damage of nucleobases in RNA; the dynamic structure of nucleic acids and their analogs in DNA replication, extra- and intra-cellular transport; molecular crowding by the use of ionic liquids; new technologies enabling the modification of gene expression via editing of therapeutic genes; the use of riboswitches; the modification of mRNA cap regions; new approaches to detect appropriately modified RNAs with EPR spectroscopy and the use of parallel and high-throughput techniques for the analysis of the structure and new functions of nucleic acids. This volume discusses how chemistry can add new frontiers to the field of nucleic acids in molecular medicine, biotechnology and nanotechnology and is not only an invaluable source of information to chemists, biochemists and life scientists but will also stimulate future research.

Dendritic cells are vital to induce potent anti-viral immune responses. It will become clear to the reader that dendritic cells often play a dual role during viral infections. On the one hand they are able to mount potent antiviral immune responses, and on the other hand several viruses, including HIV-1, use DC as a vector to be transferred from the periphery to the lymph nodes where they infect their prime target.

Genomic imprinting refers to a recently discovered phenomenon in which the expression pattern of an allele depends on whether that allele was inherited from the mother or the father. This difference in expression strategy correlates with differences in the epigenetic state of the two alleles. These epigenetic differences include DNA methylation at CpG dinucleotides, as well as modifications on the histones associated with the locus. In the simplest possible cases, the promoter region of the imprinted gene is methylated during oogenesis, but not spermatogenesis (or vice versa). This methylation (and its accompanying histone modifications) results in inactivation of the modified allele. Of course, most imprinted genes do not fall into this simplest case. The goal of this book is neither to provide a basic introduction to imprinting, nor to provide a comprehensive survey of the current state of the field (which would necessarily span multiple books). Rather, the book covers on some of the more recent advances, with the goal of drawing attention to some of the emerging subtleties and complexities associated with imprinted genes.

Structural Genomics and Drug Discovery: Methods and Protocols focuses on high throughput structure determination methods and how they can be applied to lay the groundwork for structure aided drug discovery. The methods and protocols that are described can be applied in any laboratory interested in using detailed structural information to advance the initial stages of drug discovery. 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, Structural Genomics and Drug Discovery: Methods and Protocols seeks to aid scientists in the further study into structural genomics approach as an efficient initial step toward drug discovery and the methods described will be useful to anyone interested in moving in this direction.

Chromosomes Today, Volume 13 includes the plenary lectures presented at the 13th International Chromosome Conference, covering the most recent advances in the studies on chromosomes. The contributions in this volume were presented by some of the world's leaders in cytogenetic and molecular research and outline the present status of knowledge on the composition, structure, function and evolution of chromosomes, including, among others, the advancement of the human genome project. The use of cytogenetic studies has greatly increased in the last few years, resulting in a progressive improvement in the available methods that has consequently allowed a more detailed analysis of the molecular organization of eukaryotic chromosomes and a precise in situ localisation of specific gene sequences. This volume of Chromosomes Today provides up-to-date information regarding the topics at the forefront of chromosome research: genetic regulation, imprinting, DNA duplication, meiotic pairing, and the regulation of the...

This volume provides a timely and thorough review of the current state of understanding of a fascinating type of cell that is capable of forming many or all cells in the body. In humans and other mammals embryonic stem cells, the immediate offspring of the fertilized egg, are capable of forming any type of cell in the body. Moreover stem cells are present in many different tissues in adults that are capable of dividing and differentiating into the specific cell types that comprise the organ in which they reside.

A major focus of the book is to provide the reader with up-to-date information on the molecular mechanisms that regulate the proliferation, differentiation and survival of stem cells, and how aging and age-related disease impacts on stem cells. Leading authorities detail the properties and therapeutic potential of embryonic stem cells and stem cells of the nervous and immune systems, muscle and bone. Particularly exciting are emerging technologies for using stem cells to treat human age-related diseases including cardiovascular disease, diabetes, neurodegenerative disorders such as Parkinson's and Alzheimer's diseases.

This book will be a valuable reference for developmental biologists and for scientists and clinicians who study and treat a variety of diseases.

International Review of Cytology presents current advances and comprehensive reviews in cell biology--both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.
Key Features
* Authored by some of the foremost scientists in the field
* Provides up-to-date information and directions for future research
* Valuable reference material for advanced undergraduates, graduate students and professional scientists

Precis This book is a treatise about the origin of cancers. I would like to convince readers that the basic tenets of the theory of a stem-cell origin of cancers also constitute a unified theory of cancer. Stem-cell origin of normal (and cancer) cells: Vitruvian version Every truth passes through three stages before it is recognized. In the first it is ridiculed, in the second, it is opposed, in the third, it is regarded as self-evident. - Arthur Schopenhauer v vi Preface Every person has a unique story to tell. My story is about cancer. Cancer touches the lives of countless people. Often enough, it leaves indelible tracks. Many lives have been lost; others are forever changed. For those who confront this deadly scourge, there is a sense of urgency, if not of desperation. For those who face im- nent death, life becomes even more precious and carries a special meaning. As an oncologist, I am touched daily by cancer. I feel its inception, evolution, and aft- math. It seems as though we are fighting an incessant war against cancer at the front line in the trenches. This is my story about cancer. Some people are terrific storytellers. Others have incredible tales to tell.

The medical profession requires extensive training and preparation in order to ensure the success and competency of future doctors and healthcare professionals. With an emphasis on professional development and medical education, current professionals in this field acknowledge the importance of residency programs and training in the professional development of future doctors. Optimizing Medicine Residency Training Programs presents a comprehensive overview of chapters ranging from the history of medicine to opportunities and research for further exploration geared toward the professional development and medical training for the next generation of doctors and healthcare professionals. This publication is an essential reference source for academicians, practitioners, and professionals interested in the education and training of modern medical professionals.