..The human body is made up of trillions of tiny cells that cannot be seen by the naked eye. The functioning units inside these cells are macromolecules that need to travel in the three-dimensional cell-space to distances ten thousand times their size. This movement is highly ordered, requires energy and takes place on molecular tracks that serve as a sophisticated transport system—somewhat equivalent to the multimodal rail-highway-river networks of large metropolises. All the systems of the human body depend on the efficient delivery of macromolecules to their right destination at the right time—both within and between cells. Breakdown of this traffic system results in a variety of diseases including diabetes, cancer and heart disease, as well as immunological, neurological and developmental disorders. During the last half a century, scientists have made a quantum leap in unraveling the mysteries of trafficking inside cells. The three sections of this book together cover the past, present and future of this rapidly developing and intriguing field.

..Protein transport into the endoplasmic reticulum (ER) is just one aspect of the general cell biology topic of intracellular protein sorting. This larger picture also includes protein transport into other organelles of the eukaryotic cell (chloroplasts, mitochondria, nucleus, peroxisomes), protein export from bacteria, vesicular transport that delivers to its final destination most of what has been transported into the ER, and protein export from the ER that is associated with protein degradation (termed ERAD). Over the years, protein transport into the ER also has become part of the quest to understand the various roles of molecular chaperones under non-stress conditions and of the ribosomal tunnel exit as the decisive site for molecular triage of nascent polypeptide chains.

..Both from a morphological and a functional point of view, the nucleus is central to modern cell biology. Transport of proteins and RNAs between the nucleus and the cytoplasm continues to be a fascinating research topic on its own. Furthermore, it affects many aspects of gene expression and general cellular functions and has far-reaching implications for human health.
..In this book, we cover a wide range of topics from the nuclear transport field. Individual chapters deal with the general concepts of nucleocytoplasmic transport, with various transport pathways like nuclear protein import, mRNA export and tRNA trafficking, and with the molecular mechanisms that govern macromolecular exchange between the two compartments. Others address new technologies that will help to answer open questions in the future. Together, we hope to provide a collection of reviews that should be useful for experts in the field, as well as for a wider audience.

..Cockayne syndrome (CS) is a rare autosomal genetic disorder that was first identified almost 62 years ago by Alfred Cockayne and was named after him. The earliest publication record (PubMed) available is a paper by Marie et al in 1958. Since then 815 research papers including excellent reviews have been published (PubMed, December 2008), yet we are a long way from fully understanding the exact molecular mechanisms of this disease. Ironically, like many other inborn genetic defects, CS is still incurable; the mean life expectancy of the patients is 12.5 years. Major milestones in the study of CS were the discovery that the patients have a defect in DNA repair, the identification of the two complementation groups CSA and CSB, and the finding that CS cells were defective in the specialized pathway of nucleotide excision repair, transcriptional-coupled repair (TCR), that removes certain lesions from actively transcribed DNA. The editor of this book (SIA) has considerable interest in this field; recent studies have revealed a number of new enzymes (unpublished data) that may be responsible for the scavenge of ROS. Our future studies might show if deficiency of any of these newly discovered enzymes (as a result of genetic mutations) may lead to the neurodegeneration and other ROS‑induced diseases. We hope that this book will stimulate both experts and novice researchers in the field with excellent overview of the current status of research and pointers to future research goals. The insights gained may also be valuable for the development of new therapeutic regimens for dealing with the clinical problems raised by this rare but devastating human condition.

..Cell migration is an extremely complex but also a carefully orchestrated process. It involves the constant reconstruction of the cell shape, in order to adapt to an ever‑changing plethora of external and internal stimuli. Time lapse movies of migrating cells often demonstrate a vigorous ruffling activity of the plasma membrane at the cell periphery, specifically at the forefront of the cells. From the film pictures, the motor underlying these activities might seem to be the flow of membranes and the “lipid flow model” for cell migration got a lot of attention during the eighties. The model stated that cell migration is primarily driven by a flow of lipid vesicles from the rear end to the leading end of the cells and it also stated an intimate relation between cell migration and the endocytic cycle. However, this model turned out to be, if not entirely wrong, at least incomplete, since it failed to take into account the activity of the cytoskeleton. We have barely started to recognise the mechanisms underlying the communication between the machinery for membrane dynamics and the regulators of cytoarchitecture. However, it is my sincere hope that this book will help to convince the reader that numerous vital cellular processes occur at the interface between lipid bilayers and proteins.

..This book reviews current understanding of the biological roles of the signal transducer and activator of transcription (STAT) proteins and their dysregulation in diseases. STAT proteins were named after their role as signal transducers and activators of transcription. STAT proteins are highly conserved among species, thus reflecting the importance of these transcription factors in controlling processes such as development, cell growth and homeostasis. STAT1 and STAT2 were the first STAT genes identified in the interferon signal transduction pathways. Since then seven more STATs have been identified including STAT3, STAT4, STAT5A, STAT5B and STAT6. The enormous amount of studies on STAT proteins over the past decade has enhanced our understanding of how STAT proteins at the biochemical and molecular level regulate gene expression.

..Ataxia telangiectasia (AT) is an incurable, rare autosomal recessive genetic disorder which affects approximately one in 40,000‑100,000 and the carrier frequency is estimated to be 1:100‑200. In the United Kingdom it affects 1 in 300,000 live births amounting to about 5 or 6 cases per year. Although the medial survival rate of affected persons is between 19‑25 years, due to genetic heterogeneity, the survival rate can be fairly variable. In rare cases, however, patients survive into their third decade. The longest living patient on record died at age 34 years. Although the disease may have been identified earlier, according to PubMed the first published report on AT was in 1958. These authors described the disease to be of a slowly progressive type; the patient suffered from sinopulmonary infection, which must have been due to a deficiency in the immune system, that was discovered later in AT patients. Since this publication, 4720 research papers including a number of excellent reviews have appeared (PubMed data, September, 2008). Results from these studies have provided exciting information on a multiplicity of hitherto unknown complex processes of sensing DNA damage, cell signalling, protein/protein interactions and their post‑translational processing, involving activities from control of redox state to repair of double strand DNA breaks (DSB), with outcomes that include apoptosis and carcinogenesis. Despite a huge volume of research already carried out, we are still some distance away from a complete understanding of the molecular mechanisms of AT, and there is no evidence that interest in this disease is waning. Hence this book should provide both expert and novice researchers in the field with an excellent overview of the current status of research and pointers to future research goals.

..This volume is a timely and comprehensive description of the many facets of DNA and RNA modification-editing processes and to some extent repair mechanisms. Each chapter offers fundamental principles as well as up to date information on recent advances in the field (up to end 2008). They ended by a short ‘conclusion and future prospect’ section and an exhaustive list of 35 to up to 257 references (in average 87). Contributors are geneticists, structural enzymologists and molecular biologists working at the forefront of this exciting, fast-moving and diverse field of researches. This book will be a major interest to PhD students and University teachers alike. It will also serve as an invaluable reference tool for new researchers in the field, as well as for specialists of RNA modification enzymes generally not well informed about what is going on in similar processes acting on DNA and vice-versa for specialists of the DNA modification-editing and repair processes usually not much acquainted with what is going on in the RNA maturation field. The book is subdivided into 41 chapters (740 pages). The common links between them are mainly the enzymatic aspects of the different modification-editing and repair machineries: structural, mechanistic, functional and evolutionary aspects. It starts with two general and historical overview of the discovery of modified nucleosides in DNA and RNA and corresponding modification-editing enzymes. Then follows eleven chapters on DNA modification and editing (mechanistic and functional aspects). Two additional chapters cover problems related to DNA/RNA repair and base editing by C-to-U deaminases, followed by three chapters on RNA editing by C-to-U and A-to-I type of deamination. Discussions about interplay between DNA and RNA modifications and the emergence of DNA are covered in two independent chapters, followed by twenty chapters on different but complementary aspects of RNA modification enzymes and their cellular implications. The last chapter concerns the description of the present state-of-the art for incorporating modified nucleosides by in vitro chemical synthesis. At the end of the book, six appendicies give useful details on modified nucleosides, modification-editing enzymes and nucleosides analogs. This information is usually difficult to obtain from current scientific literature.

..For many years liver surgery has been considered major surgery, which has been often associated with a high complication rate. Although evidence suggests that better results are achieved in specialized centers with a high volume of procedures, nevertheless liver resections are now carried out in most of the general surgery divisions. Beside the fact that I still believe that liver surgery should be a field of trained specialists, in editing this book I have attempted to cover for the general surgeon all the main topics of liver surgery and to review the very latest innovative developments. Eminent surgeons from different countries agreed to contribute their own views, opinions and results in the management of primary and secondary liver tumours. The book covers most of the topics which are essential elements in modern liver surgery: applied anatomy of the liver with its radiological demonstration, prognostic indicators and staging systems, portal vein embolization, vascular occlusion, intraoperative ultrasonic guided surgery, different transection techniques. I thought necessary to give space to the radiologists in an effort to outline the extraordinary advances of interventional radiology, which have taken place in recent years. Particular consideration has been given to the aspect of avoiding and managing complications. There are also new specific contributions such as partial hepatectomy after transplantation, genetics of hepatocellular carcinoma, hepatocyte transplantation, and computer-assisted operations. Since the first report of a laparoscopic liver resection, hepatic resection using minimally invasive surgery has become increasingly more common; therefore emphasis has been given to this alternative approach. Recently introduced innovative contributions in liver transplantation are also described.

..The discovery of leptin, the obese (ob) gene product which is not expressed as a functional protein in ob/ob mice, focused the scientific community’s attention on its role as an anorexic hormone involved in the negative regulation of food intake. Almost 14 years after this breakthrough discovery and over 14,000 leptin‑related publications later, leptin is now known to participate in a wide range of biological functions that include, in addition to its early envisaged function as an adipostat, glucose metabolism, glucocorticoid synthesis, CD4+ T‑lymphocyte proliferation, cytokine secretion, phagocytosis, hypothalamic‑pituitary‑adrenal axis regulation, reproduction, cardiovascular pathology, bone formation, apoptosis and angiogenesis. In short, it is now well‑documented that leptin acts like a cytokine hormone with many pleiotropic effects. Furthermore, in recent years, it has become more and more apparent that many of leptin’s effects are acquired not only through its central action, but also through its systemic action on a peripheral level. This book focuses mainly on the relatively novel aspects of leptin’s actions.

..Leptin’s involvement in early postnatal imprinting has led to new insight into developmental programming. This highly novel aspect of leptin’s action is reviewed extensively in the final chapter of this book by the Auckland group, Vickers, Krechowec, Gluckman and Breier. In the last five years, it has been shown that at least in rodents, leptin acts as an important neurotrophic factor promoting the early postnatal maturation of neural pathways within the hypothalamus. The authors review experimental evidence, originating largely from their own work, which shows that therapeutic intervention with leptin in the rodents’ early postnatal life can potentially reverse or substantially ameliorate the consequences of developmental malprogramming, and that this effect is highly influenced by both gender and postnatal diet.