Evolutionary History of the P53 Family DNA-binding Domain: Insights from an Alvinella Pompejana Homolog


Book Description

The extremophile Alvinella pompejana, an annelid worm living on the edge of hydrothermal vents in the Pacific Ocean, is an excellent model system for studying factors that govern protein stability. Low intrinsic stability is a crucial factor for the susceptibility of the transcription factor p53 to inactivating mutations in human cancer. Understanding its molecular basis may facilitate the design of novel therapeutic strategies targeting mutant p53. By analyzing expressed sequence tag (EST) data, we discovered a p53 family gene in A. pompejana. Protein crystallography and biophysical studies showed that it has a p53/p63-like DNA-binding domain (DBD) that is more thermostable than all vertebrate p53 DBDs tested so far, but not as stable as that of human p63. We also identified features associated with its increased thermostability. In addition, the A. pompejana homolog shares DNA-binding properties with human p53 family DBDs, despite its evolutionary distance, consistent with a potential role in maintaining genome integrity. Through extensive structural and phylogenetic analyses, we could further trace key evolutionary events that shaped the structure, stability, and function of the p53 family DBD over time, leading to a potent but vulnerable tumor suppressor in humans.




How Life Works


Book Description

A cutting-edge new vision of biology that will revise our concept of what life itself is, how to enhance it, and what possibilities it offers. Biology is undergoing a quiet but profound transformation. Several aspects of the standard picture of how life works—the idea of the genome as a blueprint, of genes as instructions for building an organism, of proteins as precisely tailored molecular machines, of cells as entities with fixed identities, and more—have been exposed as incomplete, misleading, or wrong. In How Life Works, Philip Ball explores the new biology, revealing life to be a far richer, more ingenious affair than we had guessed. Ball explains that there is no unique place to look for an answer to this question: life is a system of many levels—genes, proteins, cells, tissues, and body modules such as the immune system and the nervous system—each with its own rules and principles. How Life Works explains how these levels operate, interface, and work together (most of the time). With this knowledge come new possibilities. Today we can redesign and reconfigure living systems, tissues, and organisms. We can reprogram cells, for instance, to carry out new tasks and grow into structures not seen in the natural world. As we discover the conditions that dictate the forms into which cells organize themselves, our ability to guide and select the outcomes becomes ever more extraordinary. Some researchers believe that ultimately we will be able to regenerate limbs and organs, and perhaps even create new life forms that evolution has never imagined. Incorporating the latest research and insights, How Life Works is a sweeping journey into this new frontier of the life sciences, a realm that will reshape our understanding of life as we know it.




Microbial Sulfur Metabolism


Book Description

This revealing book details recent developments in the study of the relationship between sulfur and the microbial agents that affect its metabolism. In recent years, new methods have been applied to study the biochemistry and molecular biology of reactions of the global sulfur cycle, the microorganisms involved and their physiology, metabolism and ecology. These activities have uncovered fascinating new insights for the understanding of aerobic and anaerobic sulfur metabolism.







25 Years of p53 Research


Book Description

p53 has emerged as a key tumor suppressor and important target for novel cancer therapy. This book, written by world-leading p53 researchers including many of those who have shaped the field over the past 25 years, provides unique insights into the progress of the field and the prospects for better cancer diagnosis and therapy in the future.




Robotic Radiosurgery


Book Description

Covers a wide range of topics on robotic radiosurgery. General topics on robotic radiosurgery include: 9 chapters on history, physics, radiobiology and technology and 24 chapters on CNS, non-CNS and future applications in robotic radiosurgery. Includes 157 figures and 93 tables,




Protein Misfolding, Aggregation and Conformational Diseases


Book Description

The second volume continues to fill the gap in protein review and protocol literature. It does this while summarizing recent achievements in the understanding of the relationships between protein misfoldings, aggregation, and development of protein deposition disorders. The focus of Part B is the molecular basis of differential disorders.




Genomics in Aquaculture


Book Description

Genomics in Aquaculture is a concise, must-have reference that describes current advances within the field of genomics and their applications to aquaculture. Written in an accessible manner for anyone—non-specialists to experts alike—this book provides in-depth coverage of genomics spanning from genome sequencing, to transcriptomics and proteomics. It provides, for ease of learning, examples from key species most relevant to current intensive aquaculture practice. Its coverage of minority species that have a specific biological interest (e.g., Pleuronectiformes) makes this book useful for countries that are developing such species. It is a robust, practical resource that covers foundational, functional, and applied aspects of genomics in aquaculture, presenting the most current information in a field of research that is rapidly growing. Provides the latest scientific methods and technologies to maximize efficiencies for healthy fish production, with summary tables for quick reference Offers an extended glossary of technical and methodological terms to help readers better understand key biological concepts Describes state-of-the-art technologies, such as transcriptomics and epigenomics, currently under development for future perspective of the field Covers minority species that have a specific biological interest (e.g., Pleuronectiformes), making the book useful to countries developing such species




Muscle Biophysics


Book Description

Muscle contraction has been the focus of scientific investigation for more than two centuries, and major discoveries have changed the field over the years. Early in the twentieth century, Fenn (1924, 1923) showed that the total energy liberated during a contraction (heat + work) was increased when the muscle was allowed to shorten and perform work. The result implied that chemical reactions during contractions were load-dependent. The observation underlying the “Fenn effect” was taken to a greater extent when Hill (1938) published a pivotal study showing in details the relation between heat production and the amount of muscle shortening, providing investigators with the force-velocity relation for skeletal muscles. Subsequently, two papers paved the way for the current paradigm in the field of muscle contraction. Huxley and Niedergerke (1954), and Huxley and Hanson (1954) showed that the width of the A-bands did not change during muscle stretch or activation. Contraction, previously believed to be caused by shortening of muscle filaments, was associated with sliding of the thick and thin filaments. These studies were followed by the classic paper by Huxley (1957), in which he conceptualized for the first time the cross-bridge theory; filament sliding was driven by the cyclical interactions of myosin heads (cross-bridges) with actin. The original cross-bridge theory has been revised over the years but the basic features have remained mostly intact. It now influences studies performed with molecular motors responsible for tasks as diverse as muscle contraction, cell division and vesicle transport.




Excitatory Amino Acids


Book Description

In this book emerging questions of current glutamate research are addressed and new pathways which glutamte research may take in the future discussed. Since glutamate antagonists are still the major hope for the therapy of neurodegenerative disorders in humans, research activities dedicated towards the development of such novel drugs are the focus of public attention. The book comments on the most recent discoveries in the field of neuroprotection and neurodegeneration.