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This book focuses on the expression variability of highly regulated genes in multi-cellular organisms through a multidisciplinary approach combining quantitative measurements and mathematical modeling. For this purpose, the cytokine gene Interleukin-4 (IL-4) in murine type-2 (Th2) lymphocytes was chosen as prototypical model system of an inducible gene regulated at the epigenetic and transductional level. As many cytokines, IL-4 is expressed in a probabilistic manner, but the underlying molecular mechanisms behind this phenomenon are still unresolved. Through an iterative process of quantitative measurements and mathematical analysis, the author develops a computational model able to predict several system properties. The model indicates that the heterogeneity in IL-4 expression results from a rate-limiting chromatin opening during antigenic stimulation. The rate of inactivation of the promoter is slow (on the order of a cell cycle), which increases the probability of subsequent IL-4 stimulation in the same cells. As a consequence, a previously unknown short-term memory for IL-4 induction is tested and verified experimentally. The multidisciplinary approach presented here will be hopefully useful for investigating other genes highly regulated at the epigenetic level and shows the potential of system biology in revealing new properties of complex processes.
This book provides researchers the opportunity to investigate type-2-associated diseases in their laboratories. Beginning with chapters describing various models of type-2 immunity, the volume then continues by detailing cellular protocols designed to identify, characterize, and assess the function of key adaptive and innate immune cells involved in type-2 inflammation; approaches to isolate and evaluate specific cellular subsets at the genetic, epigenetic, and molecular level; protocols to assess type-2 immunity and its relationship to organismal and metabolic systems (ex. Microbiome). This book concludes with a section that explores the use of primary human cells in evaluating relevance to the clinic. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Vital and authoritative, Type 2 Immunity: Methods and Protocols aims to provide a broad network of methods that can be used to develop a hypothesis and investigate its potential from bench to beside.
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The literature on cytokine genetics is vast, so vast that it is now practically beyond the time or logistical constraints of most scientists to successfully keep pace with it. A compilation of the latest research, Cytokine Gene Polymorphisms in Multifactorial Conditions brings together, reviews, and structures up-to-date information on polymorphism
Provides a dialogue on the nature of the membrane signals and intracytoplasmic events that provoke immunity. The debate ranges over biochemistry, physiology, molecular genetics, as well as classical cellular immunology. Input came from over 70 of the world's leading investigators.
This volume explores the foundations of ontogeny by asking how the development of living things should be understood. It explores key concepts of developmental biology, asks whether general principles of development can be discovered, and what the role of models and theories is in developmental biology.
This groundbreaking book describes the emerging field of theoretical immunology, in particular the use of mathematical models to describe the spread of infectious diseases within patients. It reveals fascinating insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. Structured around the examples of HIV/AIDS and hepatitis B, Nowak and May show how mathematical models can help researchers to understand the detailed dynamics of infection and the effects of antiviral therapy. Models are developed to describe the dynamics of drug resistance, immune responses, viral evolution and mutation, and to optimise the design of therapy and vaccines. - ;We know, down to the tiniest details, the molecular structure of the human immunodeficiency virus (HIV). Yet despite this tremendous accomplishment, and despite other remarkable advances in our understanding of individual viruses and cells of the immune system, we still have no agreed understanding of the ultimate course and variability of the pathogenesis of AIDS. Gaps in our understanding like these impede our efforts towards developing effective therapies and preventive vaccines. Martin Nowak and Robert M May describe the emerging field of theoretical immunology in this accessible and well- written text. Using mathematical modelling techniques, the authors set out their ideas about how populations of viruses and populations of immune system cells may interact in various circumstances, and how infectious diseases spread within patients. They explain how this approach to understanding infectious diseases can reveal insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. The book is structured around the examples of HIV/AIDS and Hepatitis B virus, although the approaches described will be more widely applicable. The authors use mathematical tools to uncover the detailed dynamics of the infection and the effects of antiviral therapy. Models are developed to describe the emergence of drug resistance, and the dynamics of immune responses, viral evolution, and mutation. The practical implications of this work for optimisation of the design of therapy and vaccines are discussed. The book concludes with a glance towards the future of this fascinating, and potentially highly useful, field of study. - ;... an excellent introduction to a field that has the potential to advance substantially our understanding of the complex interplay between virus and host - Nature
Proceedings of the Seventh International Conference held in New Port Beach, California, February 6-8, 1998
Gene Regulatory Networks, Volume 139 in the Current Topics in Developmental Biology series, highlights new advances in the field, with this new volume presenting interesting chapters written by an international board of authors. Topics in this release include Mouse hindbrain GRN, Xenopus endoderm GRN – organogenesis, Vertebrate limb GRN, The notochord gene regulatory network in chordate evolution: conservation and divergence from Ciona to vertebrates, Ciona early embryo GRNs, Boolean logic models, Modeling GRN response to morphogen gradient, GRN architecture, Theory of GRN evolution, Evolution of fly segmentation GRNs, GRN evolution in echinoderms, Evolution of network specificity, and more. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in the Current Topics in Developmental Biology series - Includes the latest information on gene regulatory networks