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Novartis Foundation Symposium 278

Empathy and fairness 

Chair: Chris Frith

This book brings together work from a wide range of disciplines to explain processes underlying empathy and fairness. It approaches the topic of empathy and fairness from different viewpoints, namely those of social cognitive neuroscience, developmental psychology, evolutionary anthropology, economics, and neuropathology.

Published 2006 (back to top) 

Novartis Foundation Symposium 274

Heart failure: molecules, mechanisms and therapeutic targets 

Chair: Seigo Izumo

This book describes the work of leading investigators studying the basic mechanisms of cardiac growth, function and dysfunction. There are also exciting contributions from researchers developing novel therapeutic strategies for cardiac disease. The unique feature is the discussions amongst the contributors, which always return to the same basic problem: how can new data from biological studies be used to design novel therapies for the treatment of cardiac dysfunction following myocardial infarction, hypertension and other disorders?

With its strong emphasis on translational research, this book will appeal to both scientists and clinicians interested in diminishing the impact of the current epidemic of cardiac diseases.

Published 2006 (back to top) 

Novartis Foundation Symposium 265

Stem cells: nuclear reprogramming and therapeutic applications 

Chair: John Gearhart

The nuclear envelope is the boundary between a cell’s nucleus and the surrounding cytoplasm, and consists of inner and outer membranes traversed by the nuclear pores. Stem cells are specialized cells with unique potential for self-renewal and specific cell-type commitment. These cells are uncommitted cells until a particular physiological signal turns them into differentiating and lineage-committed cells with particular physiological functions.

In 1998 investigators isolated embryonic stem cells from human embryos for the first time and were able to grow these in in vitro culture systems. Since then, stem cell-based technologies have received an enormous amount of scientific attention because of their potential for developing novel therapeutic applications. Potential clinical applications range from the production of cardiomyocytes to replace damaged heart tissue, the production of insulin-producing cells for patients with diabetes, and the generation of neurons for the treatment of patients with Parkinson’s disease or spinal cord injury.

Particular attention is paid to the factors that maintain stem cells in a pluripotent state or which drive them to create differentiated and lineage-committed cells in vitro and in vivo. Understanding stem cells at the molecular level is essential to understanding their behaviour in a physiological context. Nuclear reprogramming, the process by which a nucleus acquires developmental potential, is currently a focus of great interest in the scientific community and is covered here. It is relevant to stem cell research in general, and also to research on the cloning of animals by nuclear transfer. 

This book also covers the important ethical issues that are raised by research on stem cells, as well as are the various regulatory regimes which apply in different countries: these are likely to be influential in determining where future stem cell research is carried out.

Published 2005 (back to top) 

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Novartis Foundation Symposium 262
Biology of IGF-1: its interaction with insulin in health and malignant states

Chair: Derek LeRoith

Insulin-like growth factor (IGF-1) is the anabolic effector hormone of growth hormone. In addition to its effect on normal growth it has been linked in recent years with several types of malignancy. These include prostate cancer, ovarian cancer, and colon cancer. However, the nature of this relationship with cancer is uncertain and the linkage itself is controversial.

The IGF-1 receptors and post-signalling pathways are similar to those of insulin in spite of differences in the biological actions of these hormones. Given the similarities, IGF-1 and insulin are often considered together when the link between IGF-1 and cancer is discussed.

The clinical use of long-term growth hormone treatment is increasing, and such treatment leads to raised IGF-1 levels. Increased insulin levels are also more common as the prevalence of obesity and type 2 diabetes increase in the population. Therefore, a careful discussion of the role of IGF-1 and insulin in various cancers is urgently needed. This book arises from a meeting where these issues were examined in detail. Containing contributions from the leading scientists and clinicians in the field, this book should prove essential reading for anyone with a clinical interest in the insulin and the IGFs. 

Published 2004 (back to top)

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Novartis Foundation Symposium 259
Reversible protein acetylation

Chair: Eric Verdin

The reversible acetylation of histone on lysine residues has emerged as a major factor in the regulation of transcription in eukaryotes. All core histone proteins are acetylated and unique functional chromosomal domains are characterized by specific patterns of acetylation within their histone proteins. Functional correlations have been established between the level of acetylation of specific genes and their transcriptional activity. These complex signals are currently being elucidated in the context of the ‘histone code hypothesis’. This model posits that distinct acetylation patterns in histones, along with other post-translational modifications, serve as specific signals recognized by the nuclear transcriptional machinery. 

Histone acetylation is under the control of competing histone acetyltransferases (HATs) and histone deacetylases (HDACs). Both HATs and HDACs are represented by rapidly growing protein families. For example, more than 18 distinct HDACs have been identified in humans so far. These proteins play critical roles in a wide variety of biological functions, including transcriptional regulation, cell cycle and differentiation. The identification and characterization of HATs and HDACs has led to the realization that acetylation is not restricted to histone proteins; a growing number of important biological functions appear to be regulated via acetylation. These include DNA binding (p53), nuclear–cytoplasmic shuttling (NF-κB) and coactivator recruitment (HIV Tat protein). 

Inhibitors have been developed that specifically target either HDACs or HATs. HDAC inhibitors exhibit selective toxicity towards tumour cells and are being developed as potential anticancer drugs. This book arises from the interactions of a multidisciplinary group of scientists involved in the study of acetylation. Work over the past five years is discussed in detail with an emphasis on major unanswered questions. This novel research opens up new and exciting possibilities for drug design. 

Published 2004 (back to top)

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Novartis Foundation Symposium 257
Anaphylaxis

Chair: Stephen Galli

Anaphylaxis is an immediate-type allergic reaction involving the whole organism. It is the most life-threatening allergic condition. Although there are few exact epidemiological data regarding prevalence, estimates regarding insect sting anaphylaxis range between 1–3% in the general population, but much higher values are reported by some authors for food and drug-induced anaphylaxis. Anaphylaxis is the main acute killer of allergic individuals.

Although anaphylaxis was discovered at the beginning of the 20th century there are still many unsolved problems. These include non-IgE-mediated anaphylactoid reactions, non-immunologically mediated anaphylactoid (pseudo-allergic) reactions, pathophysiological events at the microcirculatory level, appropriate therapy for the acute reaction, strategies for prevention, public education about the problem and new approaches to prevention and therapy at the IgE level. All these subjects are discussed in this book.

Since anaphylaxis occurs acutely and is unforeseen, it is very difficult to organize controlled studies regarding therapy and prevention. Since the spectrum of symptomatology covers interdisciplinary areas (skin, respiratory, cardiovascular and gastrointestinal system), inter-disciplinary approaches are necessary for progress in the field. There is widespread uncertainty among physicians about therapy, especially regarding the problem of self-administered treatment.

In this important book, an interdisciplinary group of experts explore the pathophysiology of different types of anaphylactic and anaphylactoid reactions. Data are presented on the epidemiology of these conditions and problems concerning diagnosis, therapy and prevention are explored in detail. This thorough and up-to-date coverage of the subject will be of great interest to all clinical immunologists, researchers and physicians who deal with this important life-threatening condition. 

Published 2004 (back to top)

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Novartis Foundation Symposium 254
Immunoinformatics: bioinformatic strategies for better understanding of immune function

Chair: Hans-Georg Rammensee

The diversity of the immune system and the complexity of its regulatory pathways makes immunology a combinatorial science. Computational analysis has therefore become essential to immunology, and this has led to the emerging field of immunoinformatics. This book is the first to give thorough coverage to this new field, which aims to advance our understanding of the immune system by modelling the interactions between its components.

Biological research provides ever-deeper insights into the complexity of living organisms while computer science provides an effective means to store and analyse large volumes of complex data. Combining the two fields increases the efficiency of biological research and offers the potential for major advances in the understanding of how biological systems operate.

This book encompasses major developments in immunoinformatics, including immunological databases, sequence analysis, structure modelling, mathematical modelling of the immune system, simulation of laboratory experiments, statistical support for immunological experimentation and immunogenomics.

The difficulties in effective application of bioinformatic tools in immunology arise at both ends of the expertise spectrum. Most immunologists have only a limited understanding of sophisticated data analysis and applicability and limitations, while the average computer scientist lacks understanding of the depth and complexity of biological data. The purpose of this book is to bring together contributions from a multidisciplinary team of biologists and computer scientists to explore the issues related to better understanding of immune function and, in particular, to help apply new computer science methods to immunological research.

Published 2003 (back to top)

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Novartis Foundation Symposium 251
Autism: neural basis and treatment possibilities

Chair: Michael Rutter

This groundbreaking book brings together contributions by leading scientists from different fields in order to provide a balanced view of the spectrum of current research on autism. Four main areas of research are covered.

• Twin and family data indicate that the heritability for the underlying liability to autism exceeds 90%. These studies point to a multifactorial causation involving an interaction among a relatively small number of susceptibility genes. This is examined in detail
  
• New techniques are now available for examining the neurobiology of autism. The book contains data on imaging studies showing the contributions of different brain regions, and addresses the neuropathology of autism
  
• There has been considerable discussion in the literature on autism of the fundamental nature of the psychological deficit in children with autism. There is good evidence that 'theory of mind' deficits are associated with autism; this issue is discussed
  
• The most important practical question facing medical practitioners is how to help children with autism. Data on possible psychological or psychiatric interventions for rehabilitation of children with autism are examined in detail. Drug treatments have been disappointing in this field and one chapter addresses this problem

Other topics covered include the epidemiology of autism, immunological aspects-including the possible role of infectious agents in the pathogenesis of neurodevelopmental disorders-and language impairments. This broad-ranging, authoritative book is essential reading for anyone with an interest in autism and its treatment. 

Published 2003 (back to top)

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Novartis Foundation Symposium 247
In silico simulation of biological processes

Chair: Denis Noble

Over recent decades vast amounts of biological data have been accumulated. However, it is becoming increasingly difficult to apply traditional theoretical methods to the formulation of coherent pictures of cell and organ function because it is no longer possible for a human theorist to integrate all of the available information. Instead, computer technologies must now be used to perform this integration. This book brings together contributions from many different fields to summarize the current status of computer-assisted modelling of biological processes.

The initial chapters deal with fundamental developments in hardware, software and mathematics that underlie current approaches to biological modelling.  Next, different approaches to collating data on gene structure and function are presented. These databases form a vital resource for any investigator trying to construct an integrated picture of particular biological systems. 

Novartis Foundation Symposium 244
The genetics and biology of sex determination

Chair: Roger V. Short

Although nature employs a wide variety of sex-determining mechanisms, it is only comparatively recently that the tools have become available for these to be explored at the molecular and cellular levels. A major landmark was the discovery in 1990 of the Sry gene and the subsequent demonstration of its key role in triggering male sex determination in transgenic mice. Since that time, while other key genes in the sex-determining pathway have been uncovered, the story remains far from complete.

This ground-breaking book draws together leading researchers to review and discuss the most recent advances in the understanding of the molecular genetic pathways of sex determination. Coverage includes the genetics and biochemistry of mammalian sex determination, comparisons with other modes of sex determination, and consideration of the biology of sexual development and of the evolution of sex-determining mechanisms. A major theme running through several chapters is the value of comparative studies of sex-determining mechanisms in different species. In addition, clinical aspects and the genetic analysis of anomalies of human sexual development are also addressed. This exciting book reviews much new and exciting work in this area and identifies promising new research directions.

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Novartis Foundation Symposium 242
Endocrine facets of ageing

Chair: Johannes D. Veldhuis

Social and medical developments during the past century have led to a dramatic increase in life expectancy and hence populations in countries of the developed world in which up to half of adults are in the age range of 60-100. This has encouraged the study of organismic changes associated with healthy ageing, of which an early example is the erosion of homeostatic capabilities in multiple endocrine systems.

This book reviews and discusses the most recent advances in the understanding of the endocrine facets of ageing, drawing together findings from both basic and clinical research. The questions addressed include the following: what are the relative magnitudes and time courses of different endocrine adaptations in the ageing human and experimental animal? How do external factors influence the rates of progression of endocrine sequelae of ageing? What mechanisms underlie the disarray of endocrine axes in ageing? And what are the implications of therapeutic reconstitution with hormones in ageing? By bringing together an international and interdisciplinary group of experts, the book reviews much new and exciting work in this area and serves to identify promising new research directions.

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Novartis Foundation Symposium 240
The tumour microenvironment: causes and consequences of hypoxia and acidity

Chair: Robert J. Gillies

In recent years, there has been great interest in exploiting the hypoxic tumour microenvironment for therapeutic gain. It has also become clear that this microenvironment is acidic and thus hostile to the growth and survival of viable normal cells. These observations lead to several fundamentally important questions that form the basis for this book. What are the relationships between tumour perfusion and tumour pH? What are the effects of tumour pH and hypoxia on carcinogenesis or tumorigenesis? What are the therapeutic consequences of tumour pH? 

This exciting book brings together leading clinicians and researchers to address some of these key issues. It is hypothesized that low extracellular pH is not only an important consequence of tumour growth but may also promote further tumorigenic transformation. Furthermore, in vitro studies suggest that low pH strongly affects the efficacy of chemo- and radiotherapy. Therapeutic strategies taking into account the consequences of altered pH, or which seek to manipulate tumour pH, more be more effective than those currently employed.

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Novartis Foundation Symposium 239
Complexity in biological information processing

Chair: Terrence J. Sejnowski
2001

Many human diseases such as cancer, diabetes and neural disorders arise from the malfunction of signalling components. This is frequently not caused by a single defect but is due to alterations of multiple components of an integrated signalling network. Experimental tools to quantify such changes precisely and describe the interconnected multichain signalling pathways in health and disease in a time-resolved manner are becoming increasingly available, resulting in an exponential increase in detailed information. For the unaided human mind, classification of this wealth of data and understanding the implications for pathophysiology is getting more and more difficult. Computational tools are a prerequisite for understanding of the complex interactions in biological information processing from the vast array of experimental data. These tools are starting to take shape. They have the potential to integrate many details into a systematic analysis of the entire signalling network and enable prediction of disease states not easily recognizable from complex data sets. This approach may thus help to switch the analysis of biological signalling from descriptive to predictive science and capture in a more general way the behaviour of entire systems. This groundbreaking book explores the structural and temporal complexity in biological signalling exemplified in neuronal, immunological, humoral and genetic signal transduction networks. It contains interdisciplinary discussions between experimentalists and theoretically oriented scientists, in particular those working on computer simulations. Synthesis of experiment, theory and simulation should help to explain disorders of the regulation of complex biological networks and may lead to a new understand of many human diseases.

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Novartis Symposium 238
Gastroenteritis viruses

Chair: Mary K. Estes
2001

Gastroenteritis viruses are a major cause of morbidity and mortality in humans. Many hundreds of thousands of children die annually from rotavirus diarrhoea in the developing world, and although in industrialized countries rotavirus infection is rarely fatal, the economic burden of the disease is substantial. Human caliciviruses have emerged as a significant cause of viral gastroenteritis globally. This book contains presentations and discussions by internationally recognized experts on virus structure, replication, pathogenesis, immune response and correlates of protection, molecular-epidemiological surveillance, advances in treatment, and efforts to develop vaccines, particularly against rotavirus disease. The spectrum of viruses covered comprises rotaviruses, human caliciviruses, astroviruses, coronaviruses and viruses causing gut disease in the immunocompromized host. The book not only conveys facts but also gives ample room to lively discussions on many issues at the forefront of research and development.

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Novartis Foundation Symposium 235
Ageing vulnerability: causes and interventions 

Chair: Tom Kirkwood 
2001

Ageing at individual and population levels presents one of the greatest challenges to humankind as we enter this new century. Throughout the world today older adults are the fastest growing population groups. Mortality rates have declined in virtually all countries, raising average life expectancy in the developing countries to the high 60s, and the high 70s in the developed world.  Ageing is associated with an increased risk for development of chronic diseases that contribute to morbidity and mortality.  It is estimated that by 2020 over two-thirds of deaths in the developing world will be caused by non-communicable diseases. This fact, along with the high levels of chronic morbidity associated with ageing in developed countries, represents a potentially overwhelming stress to the health and social care systems globally.

The frontiers of knowledge in relation to human ageing have been pushed back in recent years and it is to be expected that continuous progress will be made towards understanding the basic ageing processes. Further research is now urgently needed to improve our understanding of the relationship between ageing and the pathogenesis of age-associated diseases in order to identify more effective means of prevention, amelioration and management of such disease, and reduce the social and economic impacts of population ageing and the related burden of age-associated morbidity.

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Novartis Foundation Symposium 233
The nature of intelligence

Chair: Sir Michael Rutter
2000

Evolutionary psychology and behaviour genetics are two successful and important controversial fields in the study of human behaviour, but practitioners in these two fields have different conceptions of the nature of human intelligence. Evolutionary psychologists dispute the existence of general intelligence and emphasize the differences between species. They argue that natural and sexual selection would be expected to produce intelligences that are specialized for particular domains, as encountered by particular species. Behaviour geneticists consider general intelligence to be the most fundamental aspect of intelligence and concentrate on the differences between individuals of the same species. 

This exciting book features papers and discussion contributions from leading behaviour geneticists, evolutionary psychologists and experts on intelligence that explore the differences and the tensions between these two approaches. The nature of g or general intelligence is discussed in detail, as is the issue of heritability of intelligence. The alternative approaches emphasizing domain specific intelligences are also explored, alongside wide-ranging discussions on a broad range of issues such as the biological basis for intelligence, animal models and changes in IQ scores over time. 

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Novartis Foundation Symposium 231
Neural transplantation in neurodegenerative disease: current status and new directions

Chair: Craig Venter
2000

Recent technological advances have led to a rapid acceleration in our ability to gather genetic data. The complete genetic sequences are now known for several organisms and accelerated programmes are in place for sequencing many other genomes, including human. The speed with which complete sequencing can be accomplished will continue to increase as new technologies come online. In principle, the scope for developing new diagnostic techniques and drugs is now greater than at any time in human history, but the pathway from genetic information to usable drug is a long and complex one and there are many problems. 

This exciting book brings together a high-calibre group of experts to discuss the practical application of genomic information to the development of drugs. The subjects covered include the current state of the art in sequencing technology, the applications of these new technologies to sequencing the genomes of various animals, and the challenge of proteomics. Additional contributions deal with legal and ethical implications of the new uses of genetic data, and functional genomics from the point of view of the pharmaceutical industry.

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This book examines the sophisticated mechanisms that plant use to defend themselves against attack by insects and pathogens, focusing on the networks of plant signalling pathways that underlie these defences.

In response to herbivory, plants release a complex blend of as many of 100 volatile chemicals, known as semiochemicals ('sign chemicals'). These act as an airborne SOS signal, revealing the presence of the herbivore to the predators and parasitoids that are its natural enemies. Plants also have endogenous defence mechanisms that can be induced in response to pathogens, and separate chapters deal with systemic acquired resistance, phytoalexins, and the interacting pathways in pathogen and pest resistance.

The book discusses underlying biochemical mechanisms by which plant stress leads to the biosynthesis of chemical signals from pools of secondary metabolite precursors, or even from the primary metabolism source.

Finally, consideration is given to the possibilities for exploiting these signalling pathways by plant molecular genetics. The use of plant signals and their analogues to switch on defence pathways in crop plants is covered in depth.

Bringing together contributions from entomologists, chemical ecologists, molecular biologists and plant physiologists this book is truly interdisciplinary, and will be essential reading for anyone with an interest in agricultural pest control.

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‘Homology' as a concept has become increasingly elusive during the course of the 20th Century. The central debates and controversies concern both fundamental definitions and the nature of the criteria by which homology is judged. Attempts to move away from comparative morphology to ideas based on developmental pathways have tended to founder on the fact that developmental pathways evolve and that similar cells/tissues/structures in animals will often have different developmental origins. The use of information about conserved molecules in seemingly conserved developmental processes has also proven controversial. In molecular biology, the use of the term 'homology' has also been controversial, although here the issue seems to involve primarily the criteria for assessing whether parts of genes are the same because of shared descent or for other reasons.

The contributors to the book explore these topics systematically. There are contributions on the historical development of the concept of homology and its use in population studies. Other chapters deal with issues of homology in morphological and developmental studies, in behavioural studies, and especially in studies at the level of molecular genetics.

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Chair: Lewis Wolpert
1998

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