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It has been known for a number of years that not only pathogenicity islands but also plasmids and bacteriophages are able to carry genes whose products are involved in pathogenic processes. Accordingly, such elements and their products play an important role in pathogenesis due to the intestinal E. coli as well due to Shigellae. Another interesting aspect which is reflected in different articles is that genomes evolve by acquisition of new pieces of DNA following gene transfer, but also by genome reduction. Different mechanisms include the deletion of sequences or the elimination of functions by the accumulation of point mutations or rearrangements.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases – and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume I untangles the web of these enzymes and their products, and relates them to function in health and disease. Phosphoinositide 3-kinases and 3-phosphatases have received a special focus in volume I, and recent therapeutic developments in human disease are presented along with a historical perspective illustrating the impressive progress in the field.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases – and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume II extends into the role of phosphoinositides in membrane organization and vesicular traffic. Endocytosis and exocytosis are modulated by phosphoinositides, which determine the fate and activity of integral membrane proteins. Phosphatidylinositol(4,5)-bisphosphate is a prominent flag in the plasma membrane, while phosphatidylinositol-3-phosphate decorates early endosomes. The Golgi apparatus is rich in phosphatidylinositol-4-phosphate, stressed cells increase phosphatidylinositol(3,5)-bisphosphate, and the nucleus has a phosphoinositide metabolism of its own. Phosphoinositide-dependent signaling cascades and the spatial organization of distinct phosphoinositide species are required in organelle function, fission and fusion, membrane channel regulation, cytoskeletal rearrangements, adhesion processes, and thus orchestrate complex cellular responses including growth, proliferation, differentiation, cell motility, and cell polarization.

Since the establishment of the DNA structure researchers have been highly interested in the molecular basis of the inheritance of genes and of genetic disorders. Scientific investigations of the last two decades have shown that, in addition to oncogenic viruses and signalling pathways alterations, genomic instability is important in the development of cancer. This view is supported by the findings that aneuploidy, which results from chromosome instability, is one of the hallmarks of cancer cells. Chromosomal instability also underpins our fundamental principles of understanding tumourigenesis: It thought that cancer arises from the sequential acquisition of genetic alterations in specific genes. In this hypothesis, these rare genetic events represent rate-limiting ‘bottlenecks'in the clonal evolution of a cancer, and pre-cancerous cells can evolve into neoplastic cells through the acquisition of somatic mutations. This book is written by international leading scientists in the field of genome stability. Chapters are devoted to genome stability and anti-cancer drug targets, histone modifications, chromatin factors, DNA repair, apoptosis and many other key areas of research. The chapters give insights into the newest development of the genome stability and human diseases and bring the current understanding of the mechanisms leading to chromosome instability and their potential for clinical impact to the reader.

Although creatine was discovered already in the 1830s, it is only in recent years that its crucial role for human health and general well-being has been increasingly realized and appreciated. A number of beneficial health effects have been ascribed to oral creatine supplementation, such as neuroprotective, ergogenic, anti-diabetic, anti-inflammatory, antiviral, or antitumor effects. Creatine may even improve memory and intelligence. In the present book, emphasis is placed on the intricate interplay between creatine and creatine kinase function on one hand, and proper brain function, neurodegenerative disease and/or neuroprotection on the other hand. The book also elaborates on the recently identified inborn errors of creatine biosynthesis and transport, the so-called cerebral creatine deficiency syndromes. The clinical hallmarks of these disorders are mental retardation, epilepsy, autistic-like behaviour, and speech and language delay. In addition, the muscle growth- and strength-promoting effects, the pharmacokinetics and the safety of oral creatine supplementation are discussed. Finally, the present book outlines the emerging'systems biology'approaches for understanding the pleiotropic effects of creatine and creatine kinase, and hypothesizes on the most promising and influential future avenues of research towards creatine-based nutritional strategies for the prevention of neurological disease, and for improving the quality of life in general.

This topic is a new entry in the area of cellular calcium signaling: yet, it now spans the entire area, with discoveries that cover both genetic and acquired pathologies, even offering glimpses in the direction of therapy. Cellular calcium homeostasis, and thus calcium signalling, is mainly regulated by membrane intrinsic proteins and calcium sensor proteins. Both classes may be involved in pathological processes that affect both human and animals, ranging from common and important diseases (e.g. migraine, diabetes, epilepsia, manic depression, infertility, various types of cancer, Alzheimer's disease, muscular dystrophy) to rare genetic conditions (e.g., a number of genetic heart conditions, autoimmune retinopathies, night blindness, hereditary amyloid polyneuropathy, malignant hyperthermia, cerebellar ataxia, atherothrombotic disease). Clearly, the topic has now become not only very large, but also very stimulating. Its extensive critical coverage is likely to eventually stimulate fruitful interdisciplinary discussions.