Transplant Rejection And Tolerance Advancing The Field Through Integration Of Computational And Experimental Investigations

Organ transplantation is a life-saving surgical procedure through which the functionality of a failing organ system can be restored. However, without the life-long administration of immunosuppressive drugs, the recipient’s immune system will launch a massive immune attack that will ultimately destroy the graft. Although successful at protecting the graft from an immune attack, long-term use of immunosuppressive drugs leads to serious complications (e.g., increased risk of infection, diabetes, hypertension, cardiovascular disease, and cancer). Moreover, recipients suffer from limited long-term graft survival rates due to the inability of current treatments to establish tolerance to the transplanted tissues. Thus, there is a great medical need to understand the complex network of immune system interactions that lead to transplant rejection so that new strategies of intervention can be determined that will redirect the system toward transplant acceptance while preserving immune competence against offending agents. In the past 20 years, the discovery and growing understanding of the positive and negative regulators of the activation of the immune system have fostered new interventional procedures targeting one or the other. While pre-clinical results proved the validity of these strategies, their clinical implementation has been troublesome. These results underscore the need for additional methods to determine the most effective interventions to prevent long-term transplant rejection. New tools of genomics, proteomics and metabolomics are being implemented in powerful analyses that promise the development of better, safer personalized treatments. In parallel, theoretical modeling has emerged as a tool that transcends investigations of individual mechanistic processes and instead unravels the relevant mechanisms of complex systems such as the immune response triggered by a transplant. In this way, theoretical models can be used to identify important behavior that arises from complex systems and thereby delineate emergent properties of biological systems that could not be identified studying single components. Employing this approach, interdisciplinary collaborations among immunologists, mathematicians, and system biologists will yield novel perspectives in the development of more effective strategies of intervention. The aim of this Research Topic is to demonstrate how new insight and methods from theoretical and experimental studies of the immune response can aid in identifying new research directions in transplant immunology. First, techniques from various theoretical and experimental studies with applications to the immune response will be reviewed to determine how they can be adapted to explore the complexity of transplant rejection. Second, recent advances in the acquisition and mining of large data sets related to transplant genomics, proteomics, and metabolomics will be discussed in the context of their predictive power and potential for optimizing and personalizing patient treatment. Last, new perspectives will be offered on the integration of computational immune modeling with transplant and omics data to establish more effective strategies of intervention that promote transplant tolerance.

Organ transplantation is a life-saving surgical procedure through which the functionality of a failing organ system can be restored. However, without the life-long administration of immunosuppressive drugs, the recipient's immune system will launch a massive immune attack that will ultimately destroy the graft. Although successful at protecting the graft from an immune attack, long-term use of immunosuppressive drugs leads to serious complications (e.g., increased risk of infection, diabetes, hypertension, cardiovascular disease, and cancer). Moreover, recipients suffer from limited long-term graft survival rates due to the inability of current treatments to establish tolerance to the transplanted tissues. Thus, there is a great medical need to understand the complex network of immune system interactions that lead to transplant rejection so that new strategies of intervention can be determined that will redirect the system toward transplant acceptance while preserving immune competence against offending agents. In the past 20 years, the discovery and growing understanding of the positive and negative regulators of the activation of the immune system have fostered new interventional procedures targeting one or the other. While pre-clinical results proved the validity of these strategies, their clinical implementation has been troublesome. These results underscore the need for additional methods to determine the most effective interventions to prevent long-term transplant rejection. New tools of genomics, proteomics and metabolomics are being implemented in powerful analyses that promise the development of better, safer personalized treatments. In parallel, theoretical modeling has emerged as a tool that transcends investigations of individual mechanistic processes and instead unravels the relevant mechanisms of complex systems such as the immune response triggered by a transplant. In this way, theoretical models can be used to identify important behavior that arises from complex systems and thereby delineate emergent properties of biological systems that could not be identified studying single components. Employing this approach, interdisciplinary collaborations among immunologists, mathematicians, and system biologists will yield novel perspectives in the development of more effective strategies of intervention. The aim of this Research Topic is to demonstrate how new insight and methods from theoretical and experimental studies of the immune response can aid in identifying new research directions in transplant immunology. First, techniques from various theoretical and experimental studies with applications to the immune response will be reviewed to determine how they can be adapted to explore the complexity of transplant rejection. Second, recent advances in the acquisition and mining of large data sets related to transplant genomics, proteomics, and metabolomics will be discussed in the context of their predictive power and potential for optimizing and personalizing patient treatment. Last, new perspectives will be offered on the integration of computational immune modeling with transplant and omics data to establish more effective strategies of intervention that promote transplant tolerance.

A respected resource for decades, the Guide for the Care and Use of Laboratory Animals has been updated by a committee of experts, taking into consideration input from the scientific and laboratory animal communities and the public at large. The Guide incorporates new scientific information on common laboratory animals, including aquatic species, and includes extensive references. It is organized around major components of animal use: Key concepts of animal care and use. The Guide sets the framework for the humane care and use of laboratory animals. Animal care and use program. The Guide discusses the concept of a broad Program of Animal Care and Use, including roles and responsibilities of the Institutional Official, Attending Veterinarian and the Institutional Animal Care and Use Committee. Animal environment, husbandry, and management. A chapter on this topic is now divided into sections on terrestrial and aquatic animals and provides recommendations for housing and environment, husbandry, behavioral and population management, and more. Veterinary care. The Guide discusses veterinary care and the responsibilities of the Attending Veterinarian. It includes recommendations on animal procurement and transportation, preventive medicine (including animal biosecurity), and clinical care and management. The Guide addresses distress and pain recognition and relief, and issues surrounding euthanasia. Physical plant. The Guide identifies design issues, providing construction guidelines for functional areas; considerations such as drainage, vibration and noise control, and environmental monitoring; and specialized facilities for animal housing and research needs. The Guide for the Care and Use of Laboratory Animals provides a framework for the judgments required in the management of animal facilities. This updated and expanded resource of proven value will be important to scientists and researchers, veterinarians, animal care personnel, facilities managers, institutional administrators, policy makers involved in research issues, and animal welfare advocates.

Organ Shortage: The Solutions is the latest subject in the Continuing Education series, organized by Fondation Marcel Mérieux and Université Claude Bernard in Lyon. The annual subject is chosen to reflect the status of the topical issues of the year, as taught by leading international experts. The contribution of transplantation and clinical immunology to advanced medicine is considerable and promising. The annual volumes in this series keep the reader abreast of these developments.

Introduces readers to key case studies that illustrate how theory and data can be integrated to understand wildlife disease ecology.

M. C. Roco and W.S. Bainbridge In the early decades of the 21st century, concentrated efforts can unify science based on the unity of nature, thereby advancing the combination of nanotechnology, biotechnology, information technology, and new technologies based in cognitive science. With proper attention to ethical issues and societal needs, converging in human abilities, societal technologies could achieve a tremendous improvement outcomes, the nation's productivity, and the quality of life. This is a broad, cross cutting, emerging and timely opportunity of interest to individuals, society and humanity in the long term. The phrase "convergent technologies" refers to the synergistic combination of four major "NBIC" (nano-bio-info-cogno) provinces of science and technology, each of which is currently progressing at a rapid rate: (a) nanoscience and nanotechnology; (b) biotechnology and biomedicine, including genetic engineering; (c) information technology, including advanced computing and communications; (d) cognitive science, including cognitive neuroscience. Timely and Broad Opportunity. Convergence of diverse technologies is based on material unity at the nanoscale and on technology integration from that scale.

"A compelling act of connection, leavened with humour, clear-eyed yet packed with hope." —Ann-Marie MacDonald A rare work of narrative non-fiction that illuminates a world most of us try not to see: the daily lives of the severely mentally ill, who are medicated, marginalized, locked away and shunned. Susan Doherty's groundbreaking book brings us a population of lost souls, ill-served by society, feared, shunted from locked wards to rooming houses to the streets to jail and back again. For the past 10 years, many who have cycled in and out of the locked wards of the Douglas Institute in Montreal found a friend in Susan, who volunteers on the wards and then accompanies her friends out into the world. With their full cooperation, she brings us intimate stories that challenge our views of people with mental illness. Through "Caroline Evans," a woman in her early sixties whom Susan has known since she was a bright, sunny school girl, we experience living with schizophrenia, such as when Caroline was convinced she could save her roommate from the devil by pouring boiling water into her ear... She has been through it all, including having to navigate an indifferent justice system that is incapable of serving the severely ill. Susan interleaves Caroline's story with vignettes about her other friends—stories that reveal their hopes, circumstances, personalities, humanity. Susan found that if she can hang in through the first 10-15 minutes of every coffee date with someone in the grip of psychosis, true communication results. Their "madness" is not otherworldly: instead it tells us something about how they're surviving their lives and what they've been through. The Ghost Garden carries a cargo of compassion and empathy that motivates us to re-examine our understanding of justice, society and humanity.