Neuronal Nicotinic Receptors: Pharmacology and Therapeutic Opportunities
Edited by Stephen P. Arneric and Jorge D. Brioni
Nicotine's efficacy in the treatment of pain and anxiolysis, and its usefulness as a memory enhancer, have been suspected for many years, but research into the molecular biology of nicotinic acetylcholine receptors (nAChRs) traditionally has focused on smoking cessation. Now, thanks to recent technological advances in the molecular biology and electrophysiology of nAChRs, an abundance of evidence has emerged in support of nAChR ligands in the treatment of a range of CNS disorders, including Alzheimer's disease, Parkinson's disease, neuropathic pain, attention deficit disorder, and depression.
Featuring contributions from an international team of experts in the field, this volume provides researchers and clinicians with a comprehensive review of nAChRs, their molecular biology, pharmacology, and clinical implications. Moving from the molecular to the clinical levels, the authors explore the latest developments in all areas of nAChR research, including:
* Molecular biology and biochemistry of nAChRs
* The physiological roles of nAChRs
* Pharmacokinetics of nicotine-like alkaloids
* Recent breakthroughs and emerging trends in nAChR medicinal chemistry
* Current and emerging therapeutic applications of novel nAChR ligands.

A timely, authoritative review of basic research into nAChRs and their role in the development of new therapeutic strategies in the treatment of a range of various CNS diseases, Neuronal Nicotinic Receptors: Pharmacology and Therapeutic Opportunities is required reading for neuroscientists, pharmacologists, medicinal chemists, biological psychiatrists, and psychopharmacologists.

Pancreatic cancer is a formidable disease, and advances in early detection and improved therapeutics have been slow to come forth. With new advances in molecular genetics in the field of pancreatic tumorigenesis, it is an opportune time to use these recent discoveries to enhance our understanding of pancreatic cancer biology and to improve outcomes in patients. In this volume, leading experts in the field shed light on these findings describing the mutational landscape of pancreatic cancer, including new inroads into our understanding of familial pancreatic cancer, epidemiology, the biology of K-ras signaling, and the emerging contribution of epigenetic alterations to disease initiation and progression. The distinctive pancreatic cancer-stroma ecosystem as determined by the dynamic interplay of inflammation, hallmark mutations, EMT, and cancer stem cells is described, and implications of these interactions in the context of development of novel, personalized therapeutic options are explored.

This book, featuring more than 180 high spatial resolution images obtained with state-of-the-art MDCT and MRI scanners, depicts in superb detail the anatomy of the temporal bone, recognized to be one of the most complex anatomic areas. In order to facilitate identification of individual anatomic structures, the images are presented in the same way in which they emanate from contemporary imaging modalities, namely as consecutive submillimeter sections in standardized slice orientations, with all anatomic landmarks labeled. While various previous publications have addressed the topic of temporal bone anatomy, none has presented complete isotropic submillimeter 3D volume datasets of MDCT or MRI examinations. The Temporal Bone MDCT and MRI Anatomy offers radiologists, head and neck surgeons, neurosurgeons, and anatomists a comprehensive guide to temporal bone sectional anatomy that resembles as closely as possible the way in which it is now routinely reviewed, i.e., on the screens of diagnostic workstations or picture archiving and communication systems (PACS).

This book covers all aspects of oxygen delivery to tissue, including blood flow and its regulation as well as oxygen metabolism. Special attention will be paid to methods of oxygen measurement in living tissue and application of these technologies to understanding physiological and biochemical basis for pathology related to tissue oxygenation. This book is multidisciplinary and designed to bring together experts and students from a range of research fields including biochemical engineering, physiology, microcirculation, and hematology.

The goal of this work is summarize the contribution that insertional mutagenesis has made to our understanding of cancer. A variety of insertional mutagens are presented that have been used to study a variety of tumor types in several model organisms. In addition, the impact of insertional mutagenesis in several gene therapy trials is discussed along with strategies to avoid such complications in future clinical trials.

A readily reproducible collection of established and emerging techniques for studying the interaction between proteins and ligands, including biochemical/bulk techniques, structure analysis, spectroscopy, single-molecule studies, and theoretical/computational tools. Among the highlights are surface plasmon resonance (SPR) and reflectometric biosensor approaches, high-throughput screening with confocal optics microscopy, single molecule fluorescence and fluorescence correlation spectroscopy (FCS), atomic force microscopy (AFM), crystallography of reaction intermediates, and time-resolved x-ray crystallography. The protocols follow the successful Methods in Molecular Biologya"[ series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.

This book covers the origins and subsequent history of research results in which attempts have been made to clarify issues related to cellular ageing, senescence, and age-related pathologies including cancer. Cellular Ageing and Replicative Senescence revisits more than fifty-five years of research based on the discovery that cultured normal cells are mortal and the interpretation that this phenomenon is associated with the origins of ageing. The mortality of normal cells and the immortality of cancer cells were also reported to have in vivo counterparts. Thus began the field of cytogerontology. Cellular Ageing and Replicative Senescence is organized into five sections: history and origins; serial passaging and progressive ageing; cell cycle arrest and senescence; system modulation; and recapitulation and future expectations. These issues are discussed by leading thinkers and researchers in biogerontology and cytogerontology. This collection of articles provides state-of-the-art information, and will encourage students, teachers, health care professionals and others interested in the biology of ageing to explore the fascinating and challenging question of why and how our cells age, and what can and cannot be done about it.

Conceptually unsavoury, airway mucus is vital to homeostasis in the respiratory tract. In contrast, when abnormal, mucus contributes significantly to the pathophysiology of a number of severe bronchial diseases, including asthma, chronic bronchitis and cystic fibrosis. This volume provides wide ranging and in-depth coverage of the scientific and clinical aspects of airway mucus. It commences with introductory chapters which address the biochemical and molecular biological basis of airway mucus and continues with comprehensive coverage of the various physiological and rheological aspects of respiratory secretions. The clinical aspects of the topic are then considered, with chapters discussing the involvement of mucus secretions in bacterial infection and in hypersecretory diseases of the airway. The volume concludes with a discussion of the therapeutic aspects of the topic, both in terms of the possible approaches to the treatment of mucus hypersecretion and the interaction of these drugs with airway mucus. Written by leading experts in the field, each contribution provides a comprehensive review of its particular subject. Reflecting the latest advances in this important area of respiratory research, this volume will be of great interest to scientists and clinicians working in the field of airway secretions and related areas.

Sports vision is a relatively new but fast expanding area of multi-disciplinary eye care involving not only optometrists but also dispensing opticians, ophthalmologists, athletes, sports organisations and coaches. This book deals with optimising safe and efficient vision in sport. Sports vision will be essential reading for everyone involved in sport wishing to optimise vision particularly optometrists but also ophthalmologists, athletes and trainers. 'For practitioners wishing to develop an active interest in the subject this book acts as a valuable guide to how they need to develop both their optometric and dispensing skills.' - Journal of British Contact Lens Assoc., January 1996 '..excellent.' - The Optician, March 1996 * NEW IN PAPERBACK * * * Visual training, injuries and prevention, setting up a practice, legal considerations and many other aspects of sports vision are covered in detail.

Food or calorie restriction has been shown in many short-lived animals and the rhesus monkey to prolong life-span. Life-long nutrition studies are not possible in humans because of their long survival. Studies over two to six years in healthy adult humans have, however, shown that a 20% reduction in food or calorie intake slows many indices of normal and disease-related aging. Thus, it is widely believed that long-term reduction in calorie or food intake will delay the onset of age-related diseases such as heart disease, diabetes and cancer, and so prolong life.

Over the last 20 or more years there has been a progressive rise in food intake in many countries of the world, accompanied by a rising incidence of obesity. Thus our increasing food and calorie intake has been linked to the rising incidence of cardiovascular disease and diabetes in early adult life. It is accepted that overeating, accompanied by reduced physical exercise, will lead to more age-related diseases and shortening of life-span. The answer is to reduce our calorie intake, improve our diet, and exercise more. But calorie restriction is extremely difficult to maintain for long periods. How then can we solve this problem?

Edited by a team of highly distinguished academics, this book provides the latest information on the beneficial effects of calorie restriction on health and life-span. This book brings us closer to an understanding at the molecular, cellular and whole organism level of the way forward.

An inexpensive workbook which supplements Human Anatomy Color Atlas and Text. Organized in the same manner as the atlas, with an introduction and seven anatomic regions, the workbook features black-and-white outline representations of the line drawings found in the core atlas. Students are asked to identify specified anatomical structures by filling in the appropriate parts of the outlines.

Proceedings of an international symposium, held in Ulm, Germany, September 21-24, 1994

Rhim and Kremer s state-of-the-art volume on "Human Cell Transformation: Role of Stem Cells and the Microenvironment" highlights the latest findings on the current state of human cell transformation model systems and provides the insight into the molecular and cellular changes involved in the conversion of normal cells to neoplastic cells.

Chapters cover all recently developed novel human cell models. In addition, the rapidly growing fields of knowledge regarding not only stem cells in cancer progression, but also the role of the microenvironments in human carcinogenesis are discussed. A wealth of topics is presented including:

. Derivation of epithelial, fibroblastic, and hematopoietic "in vitro" model systems

. Oncogenes

. Tumor suppressor genes

. Viral transformation

. "In vitro" model systems for viral, chemical and radiation carcinogenesis

. Cell aging

. The multistep nature of human carcinogenesis. The role of stem cells and the microenvironment in tumorigenesis

. The genes involved in multistep carcinogenesis

Unique in both scope and focus devoted solely to human cell transformation systems "Human Cell Transformation: Role of Stem Cells and the Microenvironment" provides unparalleled, in-depth coverage for cancer researchers, cell and molecular biologists, hematologists, virologists, and workers in related fields.

Essential reading for everyone who needs to be kept up-to-date in this fast-paced area

Features

O Multistep models

O Breast cancer/Stem cells

O Prostate cancer/Stem cells

O Multistep / Genes"

Aging is an almost universal process within biological systems, one which leads to a decline in functional capacity, disease onset, and eventually death. There has been much interest in recent years to elucidate the molecular mec- nisms that underlie the aging process. Many theories have been proposed since the last century that aim to explain the causes of aging. There is no one theory that completely satisfies the phenotype of aging, but genetics and environm- tal factors play an important role in the etiology of age-related pathologies and the aging process. However, there is still much to be learned about the aging process which has been termed one of the last great frontiers in biology. De- graphic changes worldwide are leading to increased average life expectancies within our populations. These changes in population characteristics will impact upon the economies of the supporting society, with increasing healthcare and infrastructural costs arising from the prevalence of age-related pathologies and other physical disabilities associated with advancing years. Many researchers worldwide are working in the attempt to identify key cellular processes through which it might one day be possible to slow down the aging process and thus increase the health span of humans. Numerous research projects-from the cellular through to tissue, organ, and whole organism studies-are currently underway to investigate the mul- factorial aging process.

This book brings together the various fields of functional genomics and systems biology that provide information on metabolic function. There is special emphasis on the identification of drug targets. The book includes practical examples from the various "omic" sciences as well as theoretical examples of how integrated knowledge of these sciences can be applied to drug discovery. It is of interest to researchers in the pharmaceutical drug discovery environment.

This conference and monograph were the result of many collective efforts. The whole concept was formulated one early Wednesday morning at our weekly research meeting at Children's Hospital in our division of urology. We have been most fortunate to have a close collaboration with Bob Levin, Ed Macarak, and Pam Howard who have helped steer the course of our division's growing interest in basic science. At our weekly meetings our laboratory fellow will summarize their current work. Other ongoing areas of investigation in our labs and elsewhere are discussed. We have always made an effort to try and understand what other groups are doing who are working in the area of bladder smooth muscle research. It occurred to us that the best way to really know what everyone working in this field was doing would be to sponsor a 2-day meeting where we could all gather to discuss our ongoing work. A major limitation of the annual meeting of the American Urologic Association or the urology section of the American Academy of Pediatrics is that the scientfic sessions are limited as these are meant to be primarily clinical meetings (as they should be). For this reason the idea of a meeting devoted solely to research about the urinary bladder had great appeal. In addition to allowing for longer presentations than the standard 5 to 7 minutes, every effort would be made to encourage a dialogue amongst the presenters and the audience.

This book is unique in covering a wide range of design and analysis issues in genetic studies of rare variants, taking advantage of collaboration of the editors with many experts in the field through large-scale international consortia including the UK10K Project, GO-T2D and T2D-GENES. Chapters provide details of state-of-the-art methodology for rare variant detection and calling, imputation and analysis in samples of unrelated individuals and families. The book also covers analytical issues associated with the study of rare variants, such as the impact of fine-scale population structure, and with combining information on rare variants across studies in a meta-analysis framework. Genetic association studies have in the last few years substantially enhanced our understanding of factors underlying traits of high medical importance, such as body mass index, lipid levels, blood pressure and many others. There is growing empirical evidence that low-frequency and rare variants play an important role in complex human phenotypes. This book covers multiple aspects of study design, analysis and interpretation for complex trait studies focusing on rare sequence variation. In many areas of genomic research, including complex trait association studies, technology is in danger of outstripping our capacity to analyse and interpret the vast amounts of data generated. The field of statistical genetics in the whole-genome sequencing era is still in its infancy, but powerful methods to analyse the aggregation of low-frequency and rare variants are now starting to emerge. The chapter Functional Annotation of Rare Genetic Variants is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

For courses in anatomy & physiology for health professions, and comprehensive medical assisting. Where A&P meets pathology: A stimulating exploration Anatomy, Physiology, & Disease: An Interactive Journey for Health Professionals provides an engaging introduction to interrelationships in A&P and pathology, with emphasis on clinical applications. Conversational and humorous, the text uses real-world analogies to enable true understanding - rather than memorization - and to create lasting connections. The 3rd edition presents the latest research and clinical applications in human A&P, plus new visual aids and practice opportunities. A student workbook, available separately, offers interactive exam prep resources, including concept maps and crossword puzzles. New! Also available with MyLab Health Professions By combining trusted author content with digital tools and a flexible platform, MyLab (TM) personalizes the learning experience and improves results for each student. Note: You are purchasing a standalone product; MyLab does not come packaged with this content. Students, if interested in purchasing this title with MyLab, ask your instructor to confirm the correct package ISBN and Course ID. Instructors, contact your Pearson representative for more information. If you would like to purchase both the physical text and MyLab, search for: 0135188881 / 9780135188880 Anatomy, Physiology, & Disease: An Interactive Journey for Health Professionals Plus MyLab Health Professions with Pearson eText -- Access Card Package, 3/e Package consists of: 0134876369 / 9780134876368 Anatomy, Physiology, & Disease: An Interactive Journey for Health Professionals, 3/e 0134880196 / 9780134880198 MyLab Health Professions with Pearson eText--Access Card--for Anatomy, Physiology, & Disease, 3/e

In most peroxisomal disorders the nervous system is severely affected which explains the clinical and community burden they represent. This is the first book to focus not only on the mutations causing these inherited illnesses, but also on mechanisms that regulate, suppress or enhance expression of genes and their products (enzymes). Indeed since the success and completion of the Human Genome Project all genes (coding DNA sequences) are known. However, of many, their function, and the role of the gene product has not been determined. An example is X-linked adrenoleukodystrophy, the most frequent peroxisomal disorder. Children are born healthy, but in more than 1 out of 3, demyelination of the brain starts unpredictably and they die in a vegetative state. The gene mutated in most families has been known for 10 years; but the true role of the encoded protein, ALDp, is still speculative; and within the same family, very severe and asymptomatic clinical histories co-exist, unexplained by the mutation.

One of the primary advances for the 21st century is progress beyond the need to defend the findings of behavioral genetic investigations of intelligence. With the advent of developmental behavioral genetics and molecular genetics researchers have taken their discoveries far beyond simple nature/nurture constructs to a finer understanding of how genes and environment intersect to affect cognitive function.

"Behavior Genetics of Cognition across the Lifespan" presents the state of the field in well-documented detail as noted experts examine gene-environment interactions in cognitive function from childhood into old age. Fluidity is at the heart of this coverage: normative and non-normative brain development get equal attention, and statistical, molecular, biological, brain imaging, and neurobiological approaches contribute separately and in combination to the findings.

All major life stages are examined as periods of gene-based cognitive change, including midlife, which until recently has been considered a period for marking time until "real" age-related change occurs. And the book is written so that individual chapters can be as useful on their own as the volume is as a whole. Among the topics covered in depth:

Cognitive abilities in childhood and adolescenceGenetic and environmental influences on intellectual disabilities in childhoodCognition in middle adulthoodGene by environment interplay in cognitive agingDementia: genes, environments, interactionsBrain imaging and cognition

By synthesizing where the field is today--and identifying issues that need further attention--"Behavior Genetics of Cognition across the Lifespan" is a bedrock text for behavioral geneticists, cognitive psychologists and neuroscientists."

John Rebus stands accused: on trial for a crime that could put him behind bars for the rest of his life. Although it's not the first time the legendary detective has taken the law into his own hands, it might be the last. What drove a good man to cross the line? Or have times changed, and the rules with them? Detective Inspector Siobhan Clarke faces Edinburgh's most explosive case in years, as a corrupt cop goes missing after claiming to harbour secrets that could sink the city's police force. But in this investigation, it seems all roads lead to Rebus - and Clarke's twin loyalties to the public and the police will be tested to their limit. A reckoning is coming - and John Rebus may be hearing the call for last orders...

This book provides the most up-to-date review of the simian virus 40 (SV40) minichromosome as a model for the mammalian chromosome in studies of DNA replication. It focuses on disruption of DNA replication by anticancer drugs and DNA-damaging agents. There is a strong emphasis on the unique advantages of SV40 as an experimental system for the analysis of these classes of anticancer drug mechanisms. The new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication are covered in detail to aid readers in designing and interpreting similar experiments.
Key Features
* Presents unique advantages of SV40 as an experimental system for the study of classes of anticancer drugs
* Details new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication
* Provides details to help the reader design and interpret similar experiments