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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 ge...
Internal crises and external conflict made stability a rare feature of city life in the northern Italian commnities of the Renaissance. 'Negotiating Survival' follows the many twists and turns of strategy and vision that enabled the republic to emerge transformed but intact from the enormous strains created by the Great Schism.
Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging...
Renaissance Florence has often been described as the birthplace of modern individualism, as reflected in the individual genius of its great artists, scholars, and statesmen. The historical research of recent decades has instead shown that Florentines during the Renaissance remained enmeshed in relationships of family, neighborhood, guild, patronage, and religion that, from a twenty-first-century perspective, greatly limited the scope of individual thought and action. The sixteen essays in this volume expand the groundbreaking work of Gene Brucker, the historian in recent decades who has been most responsible for the discovery and exploration of these pre-modern qualities of the Florentine Renaissance. Exploring new approaches to the social world of Florentines during this fascinating era, the essays are arranged in three groups. The first deals with the exceptionally resilient and homogenous Florentine merchant elite, the true protagonist of much of Florentine history. The second considers Florentine religion and Florence's turbulent relations with the Church. The last group of essays looks at criminals, expatriates, and other outsiders to Florentine society.
Maintenance of the information embedded in the genomic DNA sequence is essential for life. DNA polymerases play pivotal roles in the complex processes that maintain genetic integrity. Besides their tasks in vivo, DNA polymerases are the workhorses in numerous biotechnology applications such as the polymerase chain reaction (PCR), cDNA cloning, genome sequencing, nucleic acids-based diagnostics and in techniques to analyze ancient and otherwise damaged DNA. Moreover, some diseases are related to DNA polymerase defects, and chemotherapy through inhibition of DNA polymerases is used to fight HIV, Herpes and Hepatitis B and C infections. We have recently witnessed the discovery of an abundance of novel DNA polymerases in viruses, bacteria, archaea and eukaryotes with specialized properties whose physiological functions are only beginning to be understood. This book summarizes the current knowledge of these fascinating enzymes. It is intended for a wide audience from basic scientists, to diagnostic laboratories and to clinicians who seek a better understanding of these fascinating enzymes.
DNA damage is a major threat to genomic integrity and cell survival. It can arise both spontaneously and in response to exogenous agents. DNA damage can attack most parts of the DNA structure, ranging from minor and major chemical modifications, to single-strand breaks (SSBs) and gaps, to full double-strand breaks (DSBs). If DNA injuries are mis-repaired or unrepaired, they may ultimately result in mutations or wider-scale genome aberrations that threaten cell homeostasis. Consequently, the cells elicit an elaborate signalling network, known as DNA damage response (DDR), to detect and repair these cytotoxic lesions. This Research Topic was aimed at comprehensive investigations of basic and novel mechanisms that underlie the DNA damage response in eukaryotes.
An ever-increasing demand for better drugs, elevated safety standards, and economic considerations have all led to a dramatic paradigm shift in the way that drugs are being discovered and developed. Known as rational drug design, this contemporary process is defined by three main steps: the discovery of lead compounds, surgical manipulation to deve
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This volume gives the latest developments in on the mechanisms of cancer cell resistance to apoptotic stimuli, which eventually result in cancer progression and metastasis. One of the main challenges in cancer research is to develop new therapies to combat resistant tumors. The development of new effective therapies will be dependent on delineating the biochemical, molecular, and genetic mechanisms that regulate tumor cell resistance to cytotoxic drug-induced apoptosis. These mechanisms should reveal gene products that directly regulate resistance in order to develop new drugs that target these resistance factors and such new drugs may either be selective or common to various cancers. If successful, new drugs may not be toxic and may be used effectively in combination with subtoxic conventional drugs to achieve synergy and to reverse tumor cell resistance. The research developments presented in this book can be translated to produce better clinical responses to resistant tumors.