This book will deal with heat shock proteins and more generally with stress-related inducible gene expression as a pleiotropic adaptive response to stress. It presents a textbook-like overview of the field not only to heat shock experts, but to physiologists, pharmacologists, physicians, neuropsychologists and others as well. It is intended to be a state-of-the-art and perspective book rather than an up-to-date presentation of recent data. It should provide a basis for new experimental approaches to fields at the edge of the classical heat shock field. Drugs, UV irradiation and environmental toxics will considered as important modulators of the stress response. Radical scavengers such as superoxide dismutases and inducible regulatory proteins of metallic ion status such as ferritin as well as immunophilins and protein disulfide isomerases will be considered within the frame of stress proteins. The potential practical applications of heat shock proteins in toxicology and medicine for the diagnosis, prognosis and eventually therapy of clinical conditions associated with an increased oxidative burden will be outlined. The role of heat shock proteins in the modulation of immune responses will also be included. The book considers heat shock from a broad perspective including fields for which heat-shock may become of importance in the very near future such as cellular responses to environmental stresses and complex stress responses under specific conditions. It was also felt timely to incorporate a whole section on medical and technological applications of stress proteins.

Protein homeostasis, or “Proteostasis”, lies at the heart of human health and disease. From the folding of single polypeptide chains into functional proteins, to the regulation of intracellular signaling pathways, to the secreted signals that coordinate cells in tissues and throughout the body, the proteostasis network operates to support cell health and physiological fitness. However, cancer cells also hijack the proteostasis network and many of these same processes to sustain the growth and spread of tumors. The chapters in this book are written by world experts in the many facets of the proteostasis network. They describe cutting-edge insights into the structure and function of the major chaperone and degradation systems in healthy cells and how these systems are co-opted in cancer cells and the cells of the tumor microenvironment. The chapters also cover therapeutic interventions such as the FDA-approved proteasome inhibitors Velcade and Krypolis as well as other therapies currently under clinical investigation to disarm the ability of the proteostasis network to support malignancy. This compendium is the first of its kind and aims to serve as a reference manual for active investigators and a primer for newcomers to the field. This book is dedicated to the memory of Susan Lindquist, a pioneer of the proteostasis field and a champion of the power of basic scientific inquiry to unlock the mechanisms of human disease. The chapter “Reflections and Outlook on Targeting HSP90, HSP70 and HSF1 in Cancer: A Personal Perspective” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Stresses which arise in bioreactors can influence process performance considerably. Recent molecular biological investigations indicate that stress caused by fluid dynamical effects and extreme values of process variables and toxic substances cause similar responses in the cells. These molecular fundamentals, as well as quantitative evaluation of fluid dynamical stresses and, their effects on microorganisms, animal and plant cells and proteins are treated in this volume.

This book, for the first time, comprehensively assembles and analyzes a large body of information on the role of the fundamental mechanism of the protein biosynthesis pathway, translation, in cancer biology. It systematically explores the function of the translation machinery and its regulation, including cell signaling, in the development, maintenance and progression of human cancer. The work presented here unveils the tremendous potential and applications of this vast and exciting branch of genetic, biochemical and molecular science in cancer medicine and drug development. Chapters contributed by experts in the field take the reader on a journey that starts with a dissection of the translation machinery and its regulation in norm and cancer. Later chapters characterize etiological and pathogenetic roles that translation plays in specific cancer types. Various aspects of diagnostic, prognostic and therapeutic significance of the translation machinery and its control in cancer are discussed. Readers will discover the importance of the process of translation and its regulatory mechanisms in physiology and cancer biology. The chapters and the numerous illustrations included here were contributed by expert scientists and clinicians from renowned academic and clinical establishments in Canada, the United States of America, the United Kingdom, Italy, France, Belgium, Spain, Germany and Australia. The book conveys information and knowledge that may interest a broad range of students and scholars ranging from basic scientists to clinicians and drug developers seeking to better understand the protein synthesis and its aberrations in cancer biology and cancer medicine.

An enduring controversy in evolutionary biology is the genetic basis of adaptation. Darwin emphasized "many slight differences" as the ultimate source of variation to be acted upon by natural selection. In the early 1900’s, this view was opposed by "Mendelian geneticists", who emphasized the importance of "macromutations" in evolution. The Modern Synthesis resolved this controversy, concluding that mutations in genes of very small effect were responsible for adaptive evolution. A decade ago, Allen Orr and Jerry Coyne reexamined the evidence for this neo-Darwinian view and found that both the theoretical and empirical basis for it were weak. Orr and Coyne encouraged evolutionary biologists to reexamine this neglected question: what is the genetic basis of adaptive evolution? In this volume, a new generation of biologists have taken up this challenge. Using advances in both molecular genetic and statistical techniques, evolutionary geneticists have made considerable progress in this emerging field. In this volume, a diversity of examples from plant and animal studies provides valuable information for those interested in the genetics and evolution of complex traits.