Mesenchymal Stem Cells In Human Health And Diseases

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Mesenchymal Stem Cells in Human Health and Diseases

Author : Ahmed El-Hashash
Publisher : Academic Press
ISBN 13 : 0128197137
Total Pages : 228 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis Mesenchymal Stem Cells in Human Health and Diseases by : Ahmed El-Hashash

Download or read book Mesenchymal Stem Cells in Human Health and Diseases written by Ahmed El-Hashash and published by Academic Press. This book was released on 2020-01-06 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal Stem Cells in Human Health and Diseases provides a contemporary overview of the fast-moving field of MSC biology, regenerative medicine and therapeutics. MSCs offer the potential to dramatically reduce human suffering from disease. Numerous MSC-based studies are ongoing each year, each offering hope for novel treatments in human disease. This book provides information on MSC application in well-studied human diseases and tissue repair/regeneration and recent advances in their research and treatment. These discoveries are placed within the structural context of tissue and developmental biology in sections dealing with recent advances in our understanding of MSC biology. Includes insights ranging from MSC biology and development through the derivation and identification and properties of MSCs Helps to identify potential innovative solutions for restoring normal morphogenesis and/or regeneration of diseased organs Discusses the fact-based promise of MSC therapeutics and regenerative medicine in the real world

Mesenchymal Stem Cell Therapy

Author : Lucas G. Chase
Publisher : Springer Science & Business Media
ISBN 13 : 1627032002
Total Pages : 458 pages
Book Rating : 4.6/5 (27 download)

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Book Synopsis Mesenchymal Stem Cell Therapy by : Lucas G. Chase

Download or read book Mesenchymal Stem Cell Therapy written by Lucas G. Chase and published by Springer Science & Business Media. This book was released on 2012-12-12 with total page 458 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past decade, significant efforts have been made to develop stem cell-based therapies for difficult to treat diseases. Multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), appear to hold great promise in regards to a regenerative cell-based therapy for the treatment of these diseases. Currently, more than 200 clinical trials are underway worldwide exploring the use of MSCs for the treatment of a wide range of disorders including bone, cartilage and tendon damage, myocardial infarction, graft-versus-host disease, Crohn’s disease, diabetes, multiple sclerosis, critical limb ischemia and many others. MSCs were first identified by Friendenstein and colleagues as an adherent stromal cell population within the bone marrow with the ability to form clonogenic colonies in vitro. In regards to the basic biology associated with MSCs, there has been tremendous progress towards understanding this cell population’s phenotype and function from a range of tissue sources. Despite enormous progress and an overall increased understanding of MSCs at the molecular and cellular level, several critical questions remain to be answered in regards to the use of these cells in therapeutic applications. Clinically, both autologous and allogenic approaches for the transplantation of MSCs are being explored. Several of the processing steps needed for the clinical application of MSCs, including isolation from various tissues, scalable in vitro expansion, cell banking, dose preparation, quality control parameters, delivery methods and numerous others are being extensively studied. Despite a significant number of ongoing clinical trials, none of the current therapeutic approaches have, at this point, become a standard of care treatment. Although exceptionally promising, the clinical translation of MSC-based therapies is still a work in progress. The extensive number of ongoing clinical trials is expected to provide a clearer path forward for the realization and implementation of MSCs in regenerative medicine. Towards this end, reviews of current clinical trial results and discussions of relevant topics association with the clinical application of MSCs are compiled in this book from some of the leading researchers in this exciting and rapidly advancing field. Although not absolutely all-inclusive, we hope the chapters within this book can promote and enable a better understanding of the translation of MSCs from bench-to-bedside and inspire researchers to further explore this promising and quickly evolving field.

Stem Cells and Human Diseases

Author : Rakesh K. Srivastava
Publisher : Springer Science & Business Media
ISBN 13 : 9400728018
Total Pages : 633 pages
Book Rating : 4.4/5 (7 download)

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Book Synopsis Stem Cells and Human Diseases by : Rakesh K. Srivastava

Download or read book Stem Cells and Human Diseases written by Rakesh K. Srivastava and published by Springer Science & Business Media. This book was released on 2012-01-31 with total page 633 pages. Available in PDF, EPUB and Kindle. Book excerpt: The main objective of this book is to provide a comprehensive review on stem cells and their role in tissue regeneration, homeostasis and therapy. In addition, the role of cancer stem cells in cancer initiation, progression and drug resistance are discussed. The cell signaling pathways and microRNA regulating stem cell self-renewal, tissue homeostasis and drug resistance are also mentioned. Overall, these reviews will provide a new understanding of the influence of stem cells in tissue regeneration, disease regulation, therapy and drug resistance in several human diseases.

Lung Stem Cells in Development, Health and Disease

Author : Nikolic, Marko Z.
Publisher : European Respiratory Society
ISBN 13 : 1849841349
Total Pages : 395 pages
Book Rating : 4.8/5 (498 download)

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Book Synopsis Lung Stem Cells in Development, Health and Disease by : Nikolic, Marko Z.

Download or read book Lung Stem Cells in Development, Health and Disease written by Nikolic, Marko Z. and published by European Respiratory Society. This book was released on 2021-04-01 with total page 395 pages. Available in PDF, EPUB and Kindle. Book excerpt: Most organs in the adult human body are able to maintain themselves and undergo repair after injury; these processes are largely dependent on stem cells. In this Monograph, the Guest Editors bring together leading authors in the field to provide information about the different classes of stem cells present both in the developing and adult lung: where they are found, how they function in homeostasis and pathologic conditions, the mechanisms that regulate their behaviour, and how they may be harnessed for therapeutic purposes. The book focuses on stem cells in the mouse and human lung but also includes the ferret as an increasingly important new model organism. Chapters also discuss how lung tissue, including endogenous stem cells, can be generated in vitro from pluripotent stem cell lines. This state-of-the-art collection comprehensively covers one of the most exciting areas of respiratory science

Developmental and Stem Cell Biology in Health and Disease

Author : Ahmed El-Hashash
Publisher : Bentham Science Publishers
ISBN 13 : 1681082195
Total Pages : 261 pages
Book Rating : 4.6/5 (81 download)

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Book Synopsis Developmental and Stem Cell Biology in Health and Disease by : Ahmed El-Hashash

Download or read book Developmental and Stem Cell Biology in Health and Disease written by Ahmed El-Hashash and published by Bentham Science Publishers. This book was released on 2016-07-14 with total page 261 pages. Available in PDF, EPUB and Kindle. Book excerpt: Research into stem cells started in the 1960s with experiments on spleen cultures. Evans and Kaufman made a breakthrough in mouse embryo culturing and embryonic stem cell extraction in 1981, followed by the work of Thomson in 1998 on the technique for extracting human embryonic stem cells. Since then, stem cell research has rapidly expanded as a therapeutic avenue for different diseases in humans. This book explains the basic developmental biology of stem cells including the development of stem cells during the implantation stage in utero to the regulation of stem cell division. Medical applications of stem cells in the therapy of diseases such as cancer, neurodegenerative diseases, and bone diseases are also explained in subsequent chapters. The book also explains the effect of parasitic cells on stem cell growth. Concepts in the book are explained in a simple clear manner, making this book an informative reference for non-experts, students and professionals in the field of biology and medicine.

Human Mesenchymal Stem Cells

Author : Mitchell Khan
Publisher : Nova Science Publishers
ISBN 13 : 9781536192247
Total Pages : 134 pages
Book Rating : 4.1/5 (922 download)

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Book Synopsis Human Mesenchymal Stem Cells by : Mitchell Khan

Download or read book Human Mesenchymal Stem Cells written by Mitchell Khan and published by Nova Science Publishers. This book was released on 2021 with total page 134 pages. Available in PDF, EPUB and Kindle. Book excerpt: "In Chapter 1, the COVID-19 pandemic and the damage mechanisms on the cellular level which can be ameliorated with the cellular therapies is thoroughly evaluated. Previous and ongoing stem cell clinical trial data from diseases with similar symptoms is gathered. All this accumulated data and current clinical trial results indicate that the cellular therapies could be the most effective treatment option for COVID-19 patients to ameliorate the damaged tissues and save lives. In Chapter 2, the authors examine activated mesenchymal stem cells for stroke repair. Stem Cell treatment has shown recovery in animal models of stroke, indicating an improved regenerative and repair potential. Though stem cells are still being used in clinical trials, there is no evidence that they enhance recovery in ischemic stroke patients. Nevertheless, the multipotent mesenchymal stem has widely been explored for stroke recovery. An'Activated MSC' as a therapeutic alternative to tackling ischemic stroke is proposed, thereby the activation of MSCs by cytokines, growth factors, hypoxia, pharmacological drugs, etc., could be a novel approach to improving stroke patients' responses to receiving MSCs. In Chapter 3, the potential benefits of in vitro culture of therapeutic stem cells in the presence of HB along with the ketogenic diet, whereby higher physiological concentrations of ketone bodies can be achieved in vivo, as an adjuvant to stem cell transplantation is assessed"--

Mesenchymal Stem Cell Derived Exosomes

Author : Yaoliang Tang
Publisher : Academic Press
ISBN 13 : 0128004975
Total Pages : 288 pages
Book Rating : 4.1/5 (28 download)

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Book Synopsis Mesenchymal Stem Cell Derived Exosomes by : Yaoliang Tang

Download or read book Mesenchymal Stem Cell Derived Exosomes written by Yaoliang Tang and published by Academic Press. This book was released on 2015-09-02 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal stem cell-derived exosomes are at the forefront of research in two of the most high profile and funded scientific areas – cardiovascular research and stem cells. Mesenchymal Stem Cell Derived Exosomes provides insight into the biofunction and molecular mechanisms, practical tools for research, and a look toward the clinical applications of this exciting phenomenon which is emerging as an effective diagnostic. Primarily focused on the cardiovascular applications where there have been the greatest advancements toward the clinic, this is the first compendium for clinical and biomedical researchers who are interested in integrating MSC-derived exosomes as a diagnostic and therapeutic tool. Introduces the MSC-exosome mediated cell-cell communication Covers the major functional benefits in current MSC-derived exosome studies Discusses strategies for the use of MSC-derived exosomes in cardiovascular therapies

The Biology and Therapeutic Application of Mesenchymal Cells

Author : Kerry Atkinson
Publisher : John Wiley & Sons
ISBN 13 : 111890737X
Total Pages : 1048 pages
Book Rating : 4.1/5 (189 download)

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Book Synopsis The Biology and Therapeutic Application of Mesenchymal Cells by : Kerry Atkinson

Download or read book The Biology and Therapeutic Application of Mesenchymal Cells written by Kerry Atkinson and published by John Wiley & Sons. This book was released on 2016-11-08 with total page 1048 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Biology and Therapeutic Application of Mesenchymal Cells comprehensively describes the cellular and molecular biology of mesenchymal stem cells and mesenchymal stromal cells, describing their therapeutic potential in a wide variety of preclinical models of human diseases and their mechanism of action in these preclinical models. Chapters also discuss the current status of the use of mesenchymal stem and stromal cells in clinical trials in a wide range of human diseases and disorders, for many of which there are limited, or no other, therapeutic avenues. Provides coverage on both the biology of mesenchymal stem cells and stromal cells, and their therapeutic applications Describes the therapeutic potential of mesenchymal stem and stromal cells in a wide variety of preclinical models of human diseases and their mechanism of action in these preclinical models Discusses the current status of mesenchymal stem and stromal cells in clinical trials in a wide range of human diseases and disorders, for many of which there are limited, or no other, therapeutic avenues Written and edited by leaders in the field The Biology and Therapeutic Application of Mesenchymal Cells is an invaluable resource for those studying stem cells, cell biology, genetics, gene or cell therapy, or regenerative medicine.

Mesenchymal Stem Cells - Basics and Clinical Application I

Author : Birgit Weyand
Publisher : Springer
ISBN 13 : 3642356710
Total Pages : 194 pages
Book Rating : 4.6/5 (423 download)

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Book Synopsis Mesenchymal Stem Cells - Basics and Clinical Application I by : Birgit Weyand

Download or read book Mesenchymal Stem Cells - Basics and Clinical Application I written by Birgit Weyand and published by Springer. This book was released on 2014-07-08 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prospective Isolation and Characterization of Human Bone Marrow-Derived MSCs, by A. Harichandan, K. Sivasubramaniyan, H.-J. Bühring Urine as a Source of Stem Cells, by Christina Benda, Ting Zhou, Xianming Wang, Weihua Tian, Johannes Grillari, Hung-Fat Tse, Regina Grillari-Voglauer, Duanqing Pei, Miguel A. Esteban Expansion of Mesenchymal Stem/Stromal Cells under Xenogenic-Free Culture Conditions, by Sven Kinzebach, Karen Bieback Adipose-Derived Mesenchymal Stem Cells: Biology and Potential Applications, by Danielle Minteer, Kacey G Marra, J Peter Rubin Potential for Osteogenic and Chondrogenic Differentiation of MSC, by Antonina Lavrentieva, Tim Hatlapatka, Anne Neumann, Birgit Weyand, Cornelia Kasper Potential for Neural Differentiation of Mesenchymal Stem Cells, by Letizia Ferroni, Chiara Gardin, Ilaria Tocco, Roberta Epis, Alessandro Casadei, Vincenzo Vindigni, Giuseppe Mucci, Barbara Zavan Migratory Properties of Mesenchymal Stem Cells, by Thomas Dittmar, Frank Entschladen Dissecting Paracrine Effectors for Mesenchymal Stem Cells, by Stefania Bruno, Federica Collino, Ciro Tetta, Giovanni Camussi Proteomics Approaches in the Identification of Molecular Signatures of Mesenchymal Stem Cells, by Yin Xiao, Jiezhong Chen Does the Adult Stroma Contain Stem Cells?, by Richard Schäfer

Mesenchymal Stem Cells and Immunomodulation

Author : Charles J. Malemud
Publisher : Springer
ISBN 13 : 3319467336
Total Pages : 85 pages
Book Rating : 4.3/5 (194 download)

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Book Synopsis Mesenchymal Stem Cells and Immunomodulation by : Charles J. Malemud

Download or read book Mesenchymal Stem Cells and Immunomodulation written by Charles J. Malemud and published by Springer. This book was released on 2016-12-10 with total page 85 pages. Available in PDF, EPUB and Kindle. Book excerpt: This essential volume explores mesenchymal stem cells (MSCs) and their potential to suppress immune-mediated inflammation. The chapters examine applications in autoimmune diseases such as lupus, rheumatoid arthritis and multiple sclerosis; blood cancers such as leukemia and lymphoma; and reproductive complications, specifically pre-term labor and use of MSCs in vitro and in animal models to discover methods of suppressing the causal inflammatory response. It also further defines the methodologies required to develop research on MSCs in vitro into established preclinical animal models including those which are proven replicas of autoimmunity and pre-term labor, to name but two. Mesenchymal Stem Cells and Immunomodulation, part of Springer’s Stem Cell Biology and Regenerative Medicine, is an invaluable resource for researchers and clinicians working with stem cells, autoimmune disease, oncology, and reproductive medicine.

Genetic Engineering of Mesenchymal Stem Cells

Author : Jan A. Nolta
Publisher : Springer Science & Business Media
ISBN 13 : 140203959X
Total Pages : 170 pages
Book Rating : 4.4/5 (2 download)

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Book Synopsis Genetic Engineering of Mesenchymal Stem Cells by : Jan A. Nolta

Download or read book Genetic Engineering of Mesenchymal Stem Cells written by Jan A. Nolta and published by Springer Science & Business Media. This book was released on 2006-08-29 with total page 170 pages. Available in PDF, EPUB and Kindle. Book excerpt: MSC (mesenchymal stem cells) have been reported to initiate revascularization after injury, to facilitate engraftment of blood-forming stem cells, and to reduce the incidence of graft-vs. host disease through their immune-suppressive qualities. Finally, bone marrow-derived MSC have been reported to home to areas of solid tumor revascularization, and thus may be used as delivery vehicles to target ablative agents into dividing tumor cells. Recently the characteristics of human MSC from adipose (fat) tissue have also been identified. The possibility of repairing tissues, speeding stem cell engraftment, and targeting solid tumors for specific killing, using MSC easily harvested from bone marrow, or better yet, from unwanted fat tissue, holds broad appeal, and is an intriguing possibility that could have dramatic effect on health care. This book has information on how to isolate, grow, and characterize MSC from marrow and fat, and gives important insight into how these cells may be used for gene delivery and cellular therapies in the future. Updates on emerging clinical trials are given.

Mesenchymal Stem Cells

Author : Phuc Van Pham
Publisher : BoD – Books on Demand
ISBN 13 : 9535136151
Total Pages : 302 pages
Book Rating : 4.5/5 (351 download)

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Book Synopsis Mesenchymal Stem Cells by : Phuc Van Pham

Download or read book Mesenchymal Stem Cells written by Phuc Van Pham and published by BoD – Books on Demand. This book was released on 2017-11-29 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal Stem Cells: Isolation, Characterization, and Applications thoroughly presents the isolation, characterization, and some applications of mesenchymal stem cells in the clinic. The book has two parts: "Isolation and Characterization" and "Clinical Perspectives and Applications." In Part I, the subsequent chapters introduce some techniques in isolation, characterization, and purification of mesenchymal stem cells in different tissues. In Part II, some applications of mesenchymal stem cells in the popular diseases, which include cartilage regeneration, spinal cord injury, and osteoarthritis, are discussed. This book provides a succinct yet comprehensive overview of mesenchymal stem cells for advanced students, graduate students, and researchers.

Stem Cell Transplantation for Autoimmune Diseases and Inflammation

Author : Phuc Van Pham
Publisher : Springer
ISBN 13 : 3030234215
Total Pages : 163 pages
Book Rating : 4.0/5 (32 download)

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Book Synopsis Stem Cell Transplantation for Autoimmune Diseases and Inflammation by : Phuc Van Pham

Download or read book Stem Cell Transplantation for Autoimmune Diseases and Inflammation written by Phuc Van Pham and published by Springer. This book was released on 2019-08-13 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book introduces many new technologies and clinical applications of hematopoietic stem cells and mesenchymal stem cell transplantation for the treatment of autoimmune diseases and inflammatory diseases. Presented in two parts, Part 1 focuses on stem cell therapies for autoimmune disease treatment; Part 2 focuses on stem cell therapies and their application in the treatment of common inflammatory diseases, including chronic knee osteoarthritis, chronic obstructive pulmonary disease, liver cirrhosis, Crohn's Disease, Multiple Sclerosis, and more. This book is an essential source for all advanced students and researchers involved with these diseases, stem cells, or both. Stem Cell Transplantation for Autoimmune Diseases and Inflammation and the other books in the Stem Cells in Clinical Applications series are invaluable to scientists, researchers, advanced students and clinicians working in stem cells, regenerative medicine, or tissue engineering as well as cancer or genetics research.

Mesenchymal Stem Cells in Human Health and Diseases

Author : Ahmed El-Hashash
Publisher : Academic Press
ISBN 13 : 0128205334
Total Pages : 230 pages
Book Rating : 4.1/5 (282 download)

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Book Synopsis Mesenchymal Stem Cells in Human Health and Diseases by : Ahmed El-Hashash

Download or read book Mesenchymal Stem Cells in Human Health and Diseases written by Ahmed El-Hashash and published by Academic Press. This book was released on 2020-01-07 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal Stem Cells in Human Health and Diseases provides a contemporary overview of the fast-moving field of MSC biology, regenerative medicine and therapeutics. MSCs offer the potential to dramatically reduce human suffering from disease. Numerous MSC-based studies are ongoing each year, each offering hope for novel treatments in human disease. This book provides information on MSC application in well-studied human diseases and tissue repair/regeneration and recent advances in their research and treatment. These discoveries are placed within the structural context of tissue and developmental biology in sections dealing with recent advances in our understanding of MSC biology. Includes insights ranging from MSC biology and development through the derivation and identification and properties of MSCs Helps to identify potential innovative solutions for restoring normal morphogenesis and/or regeneration of diseased organs Discusses the fact-based promise of MSC therapeutics and regenerative medicine in the real world

Tissue Engineering and Regenerative Medicine

Author : Phuc Van Pham
Publisher : Springer
ISBN 13 : 303019857X
Total Pages : 225 pages
Book Rating : 4.0/5 (31 download)

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Book Synopsis Tissue Engineering and Regenerative Medicine by : Phuc Van Pham

Download or read book Tissue Engineering and Regenerative Medicine written by Phuc Van Pham and published by Springer. This book was released on 2019-08-14 with total page 225 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new series, based on a bi-annual conference and its topics, represents a major contribution to the emerging science of cancer research and regenerative medicine. Each volume brings together some of the most pre-eminent scientists working on cancer biology, cancer treatment, cancer diagnosis, cancer prevention and regenerative medicine to share information on currently ongoing work which will help shape future therapies. These volumes are invaluable resources not only for already active researchers or clinicians but also for those entering these fields, plus those in industry. Tissue Engineering and Regenerative Medicine is a proceedings volume which reflects papers presented at the 3rd bi-annual Innovations in Regenerative Medicine and Cancer Research conference; taken with its companion volume Stem Cells: Biology and Engineering it provides a complete overview of the papers from that meeting of international experts.

Human Embryonic Stem Cells

Author : Arlene Chiu
Publisher : Springer Science & Business Media
ISBN 13 : 1592594239
Total Pages : 455 pages
Book Rating : 4.5/5 (925 download)

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Book Synopsis Human Embryonic Stem Cells by : Arlene Chiu

Download or read book Human Embryonic Stem Cells written by Arlene Chiu and published by Springer Science & Business Media. This book was released on 2003-08-01 with total page 455 pages. Available in PDF, EPUB and Kindle. Book excerpt: A discussion of all the key issues in the use of human pluripotent stem cells for treating degenerative diseases or for replacing tissues lost from trauma. On the practical side, the topics range from the problems of deriving human embryonic stem cells and driving their differentiation along specific lineages, regulating their development into mature cells, and bringing stem cell therapy to clinical trials. Regulatory issues are addressed in discussions of the ethical debate surrounding the derivation of human embryonic stem cells and the current policies governing their use in the United States and abroad, including the rules and conditions regulating federal funding and questions of intellectual property.

Genetics, Evolution and Radiation

Author : Victoria L. Korogodina
Publisher : Springer
ISBN 13 : 9783319840277
Total Pages : 0 pages
Book Rating : 4.8/5 (42 download)

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Book Synopsis Genetics, Evolution and Radiation by : Victoria L. Korogodina

Download or read book Genetics, Evolution and Radiation written by Victoria L. Korogodina and published by Springer. This book was released on 2018-07-20 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is dedicated to the great scientist and outstanding individual Nikolay Wladimirovich Timofeeff-Ressovsky. The book brings together a number of brief stories/essays about Timofeeff-Ressovsky including “Stories told by himself”, and scientific chapters addressing his major research areas: genetics, radiobiology, radiation ecology and epidemiology, and evolution. Timofeeff-Ressovsky contributed to several fields of biology and established new directions of scientific research. He often repeated the phrase, which would later become famous: “Science should not be approached with the ferocity of wild animals”. In keeping with that philosophy, the issues discussed here are still open. Each scientific part starts with a current review; the chapters present leading scientific schools and views. The main theme discussed in the genetics part is mutation variability in the context of linear (replication, transcription, translation) and conformational template processes, and its dependence on phylogenetic group. In turn, the radiobiology chapters focus on the reorganization of DNA, cell, and population variability under low-dose irradiation, sparking indirect processes and adaptive response. The radiation ecology and epidemiology parts present data on the consequences of nuclear plants and related accidents for ecological systems and human beings. Here some approaches to estimating radiation risks are also offered. Evolution laws are demonstrated in the genomic universe, plant-microbe symbiosis, stabilizing and destabilizing (directional) selection. The last essay demonstrates the principles of organization operating in local animal populations, which are approached as social organisms of complex systemic nature. The chapter 'Radiation-Induced Aging and Genetic Instability of Mesenchymal Stem Cells: An Issue for Late Health Effects?' is available open access under a CC BY 4.0 license.