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Neurocutaneous Disorders : Phakomatoses and Hamartoneoplastic Syndromes
Neurocutaneous diseases are a wide group of conditions that affect the nervous system but appear as lesions of the skin. Some of the more common entities have variable forms of expression that can confuse the diagnosis; for the rare conditions it is difficult to find descriptions in the literature. Recent insights into their cellular, biochemical and molecular genetic bases have shown the essential need for a new nosology and updated genotype-phenotype correlations. The book provides an authoritative source of knowledge about these difficult problems and bridges the gap between clinical recognition and the new molecular medicine. The editors, distinguished clinicians and geneticists, assembled an internationally renowned group of collaborators, many of them the experts who first described a particular disorder or established its present accepted definition.
Neuroacanthocytosis Syndromes II
Awareness of neuroacanthocytosis disorders has increased significantly in recent years. There have been a number of important developments in the field since the publication of the first volume, Neuroacanthocytosis Syndromes. This book contains the latest research in this area. Recent advances have identified the range of mutations in the causative genes, shedding light on potential phenotypegenotype correlations. Studies of the proteins affected in these disorders have resulted in increased understanding of their functions and distribution. In vitro studies have identified potential protein interactions, which have important implications for pathophysiology. Work on erythrocyte membranes suggests mechanisms for the generation of acanthocytes. Animal models are being generated which will greatly facilitate understanding the role of gene mutations in humans, and provide the foundation for possible therapeutic interventions. In addition, advances in other neurodegenerative disorders, such as Huntington’s and Parkinson’s diseases, have implications for neuroacanthocytosis.
Morphometrics with R
The R language and environment offers a single platform to perform a multitude of analyses from the acquisition of data to the production of static and interactive graphs. This offers an ideal environment to analyze shape variation and shape change. This open-source language is accessible for novices and for experienced users. Adopting R gives the user and developer several advantages for performing morphometrics: evolvability, adaptability, interactivity, a single and comprehensive platform, possibility of interfacing with other languages and software, custom analyses, and graphs. The book explains how to use R for morphometrics and provides a series of examples of codes and displays covering approaches ranging from traditional morphometrics to modern statistical shape analysis such as the analysis of landmark data, Thin Plate Splines, and Fourier analysis of outlines.
Molecular Mechanisms of Parasite Invasion
All of the parasitic organisms highlighted in this new book represent medically important human pathogens that contribute significantly to the global burden of disease. As such there is intense interest in understanding the molecular basis of infection by these pathogens—not only with regard to their clinical relevance but also the fascinating biology they reveal. For most of the parasites discussed here the ability to penetrate biological barriers and/or to establish intracellular residence is critical to survival of the pathogen in the mammalian hosts. For other parasites, a tissue invasive phenotype is a key virulence determinant. In the ensuing 18 chapters, select members of this diverse set of protozoan parasites, as well as some examples of the extremely reduced fungal parasites classified as Microsporidia, are discussed within the context of the fascinating molecular strategies employed by these organisms to migrate across biological barriers and to establish residence within target host cells.
Microbial Root Endophytes
Plant roots may not only be colonized by mycorrhizal fungi, but also by a myriad of bacterial and fungal root endophytes that are usually not considered by the investigators of classic symbioses. This is the first book dedicated to the interactions of non-mycorrhizal microbial endophytes with plant roots. The phenotypes of these interactions can be extremely plastic, depending on environmental factors, nutritional status, genetic disposition and developmental stages of the two partners. The book deals with diversity, life history strategies, interactions, applications in agriculture and forestry, methods for isolation, cultivation, and both conventional and molecular methods for identification and detection of these endophytes. The comprehensive reviews demonstrate the high diversity of interactions and will provoke further studies to better understand the mechanisms which determine whether a plant-microbial interaction remains asymptomatic, leads to disease or to a mutualistic interaction.
Metabolomics : The frontier of systems biology
Metabolism is the sum of the chemical reactions in cells that produce life-sustaining chemical energy and metabolites. In the post-genome era, metabolism has taken on new significance for biological scientists: metabolites are the chemical basis of phenotypes that are final expressions of genomic information. This book covers research on metabolomics, ranging from the development of specialized chemical analytical techniques to the construction of databases and methods for metabolic simulation. The authors have been directly involved in the development of all the subject areas, including capillary electrophoresis, liquid chromatography, mass spectrometry, metabolic databases, and metabolic simulation. Breakthrough achievements and the future of metabolome studies are described, making this book a valuable source for researchers in metabolomics in diverse fields, such as plant, animal, cellular, microbial, pharmaceutical, medical, and genetic sciences.
Immunology, phenotype first : How mutations have established new principles and pathways in immunology
This monograph deals with the impact of classical genetics in immunology, prov- ing examples of how large immunological questions were solved, and new fields opened to analysis through the study of phenotypes, either spontaneous or induced. As broad as biology has become, there are those who do not fully understand what the genetic approach is, and how it differs fundamentally from most of the methods available to natural scientists.
Immunogenetics of Autoimmune Disease
Utoimmunity is the downstream outcome of a rather extensive and coordinated series of events that include loss of self-tolerance, peripheral lymphocyte Aactivation, disruption of the blood-systems barriers, cellular infiltration into the target organs and local inflammation. Cytokines, adhesion molecules, growth factors, antibodies, and other molecules induce and regulate critical cell functions that perpetuate inflammation, leading to tissue injury and clinical phenotype. The nature and intensity of this response as well as the physiological ability to restore homeostasis are to a large extent conditioned by the unique amino acid sequences that define allelic variants on each of the numerous participating mol ecules. Therefore, the coding genes in their germline configuration play a primary role in determining who is at risk for developing such disorders, how the disease progresses, and how someone responds to therapy. Although genetic components in these diseases are clearly present, the lack of obvious and homogeneous modes of transmission has slowed progress by prevent ing the full exploitation of classical genetic epidemiologic techniques. Furthermore, autoimmune diseases are characterized by modest disease risk heritability and m- tifaceted interactions with environmental influences. Yet, several recent discoveries have dramatically changed our ability to examine genetic variation as it relates to human disease. In addition to the development of large-scale laboratory methods and tools to efficiently recognize and catalog DNA diversity, over the past few years there has been real progress in the application of new analytical and data-manage ment approaches
Imaging in Drug Discovery and Early Clinical Trials
Efficient tools for the selection and validation of drug targets both at the preclinical and clinical level are required. Non-invasive imaging and in particular molecular imaging methods are becoming essential technologies to support drug discovery and dvelopment. Imaging provides structural, functional, metabolic and molecular readouts that are being applied to characterize a disease phenotype (diagnosis), to elucidate molecular mechanisms involved, to evaluate drug efficacy and safety, and to identify potential biomarkers of the drug's mechanism-of-action, efficacy and safety. Non-invasive imaging techniques constitute a bridge between preclinical and clinical drug evaluation. In this monograph the contribution of imaging modalities to the various stages of drug discovery and development, from early target validation to their use in clinical development programs, is described. Chapters are devoted to the description of the drug discovery process as such, to the various imaging modalities being used both preclinically and clinically, to applications of imaging during the optimization of a lead compound (addressing issues such as bioavailability and efficacy) and during the drug safety evaluation.
Heterogeneity in statistical genetics : How to assess, address, and account for mixtures in association studies
Heterogeneity, or mixtures, are ubiquitous in genetics. Even for data as simple as mono-genic diseases, populations are a mixture of affected and unaffected individuals. Still, most statistical genetic association analyses, designed to map genes for diseases and other genetic traits, ignore this phenomenon.In this book, we document methods that incorporate heterogeneity into the design and analysis of genetic and genomic association data. Among the key qualities of our developed statistics is that they include mixture parameters as part of the statistic, a unique component for tests of association. A critical feature of this work is the inclusion of at least one heterogeneity parameter when performing statistical power and sample size calculations for tests of genetic association.
Genotype - Proteotype - Phenotype Relationships in Neurodegenerative Diseases
Improved understanding of role of protein dysmetabolism in neurodegeneration promises to improve diagnoses, facilitate the development of biological markers relevant to disease pathophysiology, and provide tractable therapeutic targets. This Fondation IPSEN conference summary provides an update on the latest advances of the role of protein misfolding in the pathophysiology of neurodegenerative diseases.
Genetic Basis for Respiratory Control Disorders
The objective of the book is to supply state-of-the-art contributions about all aspects of respiratory control genetics, from the molecular to the system level. The book aims to review the full spectrum of available knowledge, which starts with early physiological studies in health and disease in humans and studies in rodents that suggested a hereditary component to respiratory control. The spectrum extends to recent work elucidating crucial molecular aspects of respiratory control development, from early embryonic specifications in the neural tube to the function of respiratory rhythm generators.
Frailty and Kidney Disease : A Practical Guide to Clinical Management
This book is of importance in nephrology, specifically nephrogeriatrics, since frailty is a condition affecting many elderly patients and which is becoming increasingly common in medical practice. As such, there is a considerable need for information to assist professionals treating these patients. The book includes chapters on the frailty syndrome (definition, evaluation and treatment), the main geriatric syndromes (gait disorder, falls, incontinence, and delirium), the main renal syndromes (acute renal injury, chronic kidney disease) as well as dialysis and kidney transplant, and the relationship between geriatrics and renal syndromes.
Evolutionary Genomics : Statistical and Computational Methods
This book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results.
Diverse Roles of Integrin Receptors in Articular Cartilage
Recent studies from the authors' laboratory and from other leading groups have shown that ß1-integrins are essential for cell signalling and communication in chondrocytes. Furthermore, ß1-integrins function as mechanoreceptors in the chondrocyte mechanotransduction pathway. Their expression is therefore essential for maintaining the chondrocyte phenotype, preventing chondrocyte apoptosis and regulating chondrocyte-specific gene expression. This book volume summarizes the work that the authors have done on ß1-integrins over the last 18 years and focuses on the expression and regulation of these proteins in chondrocytes and their role in the context of the unique function of chondrocytes within articular cartilage.
Distribution and phenotype of proliferating cells in the Forebrain of adult macaque monkeys after transient global cerebral ischemia
The authors' results show that ischemia differentially activates endogenous neural precursors residing in diverse locations of the adult primate central nervous system. A limited endogenous potential for postischemic neuronal repair exists in neocortex and striatum, but not in the hippocampus proper of the adult macaque monkey brain. The presence of putative parenchymal progenitors and of sustained progenitors in germinative centers opens novel possibilities for precursor cell recruitment.
Dendritic Cells in Clinics
Great advances have taken place in basic research and the clinical usefulness of dendritic cells (DCs). It has now been clearly established, for instance, that these cells play a crucial role in immune responses against infectious diseases and cancers. Antigen-presenting DCs are widely distributed in the body and regulate both immunity and immune tolerance. Experimental studies have provided important insights into DCs and how they can be used for treating animal models of various diseases that occur in humans. The role of these cells in pathogenesis and the treatment of human diseases is elaborately set forth in this valuable book. Researchers in the field are optimistic that DCs, already in use for treating patients with cancers, soon can be used therapeutically for patients with chronic infections, autoimmune diseases, and allergic manifestations. This volume provides a working definition of DCs and also explains the phenotypes and functions of DCs so that these can be readily understood not only by clinicians but by immunologists, researchers, and students as well.
Kindling 6
A broad array of themes concerned with research on epilepsy and kindling is covered in the book: Pathogenesis of kindling, including developmental patterns; electrophysiology; anatomy, morphology, and neural circuitry; genes, species, and strains; synaptic pharmacology and neurochemistry ; Behavioral consequences of kindling ; Drugs and interventions against kindling ; Clinical relevance of kindling for our understanding of epilepsy in patients
Comparative genomics ; RECOMB 2007, International Workshop, RECOMB-CG 2007, San Diego, CA, USA, September 16-18, 2007, Proceedings
This book provides an evolutionary conceptual framework for comparative genomics, with the ultimate objective of understanding the loss and gain of genes during evolution, the interactions among gene products, and the relationship between genotype, phenotype and the environment. The many examples in the book have been carefully chosen from primary research literature based on two criteria: their biological insight and their pedagogical merit. The phylogeny-based comparative methods, involving both continuous and discrete variables, often represent a stumbling block for many students entering the field of comparative genomics. They are numerically illustrated and explained in great detail.
Clinical metabolomics applications in genetic diseases
Helps readers discover the forefront of personalized medicine on clinical metabolomics and its applications in genetic diseases. This comprehensive guide offers a functional relationship map between cell components and genetic variations in various diseases, providing insights that can be applied to personalized medicine. Covers the latest developments in metabolomics for health, with practical guidance for clinical experts looking to advance their laboratory techniques and career. The metabolomics profile is a powerful tool that has revolutionized our understanding of the relationship between genetics, clinical readouts, and disease outcomes. By integrating metabolomics with genomics and clinical phenotypes, the authors have developed diagnostic and prediction models that have vastly improved patient outcomes and deepened the understanding of disease mechanisms.
