Elucidating the Molecular Function of Reprolysin Metalloproteases in Tick-host-pathogen Interactions


Book Description

Ticks are ectoparasites that attach to their host for many days to weeks, feeding to engorgement and continuing their species life cycle. The mechanisms behind the successful feeding and manipulation of host immune responses have been associated with the secretion of their specialized saliva. Tick saliva includes a variety of modulatory molecules that must disrupt and counteract defense mechanisms, including a variety of proteases. Reprolysin Metalloproteases, in the Zn2+ dependent family, is secreted as a proenzyme and is shown to have proteolytic activity, degrading fibrinogen and gelatinase activity, as well as disturbing homeostasis.12 Previous work with the Amblyomma americanum sialotranscriptome identified over 40 metalloproteases secreted in the saliva during the ticks' feeding. A. americanum is a carrier of multiple diseases, including Ehrlichia chaffeensis, the causative agent of Human Monocyte Ehrlichiosis. This experiment consisted of two main goals: the first was to characterize A. americanum Reprolysin Metalloproteases, and the second to gain a better insight into the relationship between this tick and E. chaffeensis, a pathogen very understudied within the tick vector and has proved problematic for animal model studies. --Page ii.




African Ixodoidea


Book Description




Toxins and Hemostasis


Book Description

Circulation of blood is vital for the survival of vertebrates, including man. Mainly, it plays an important role in carrying food nutrients and oxygen to every tissue and organ and in removing all waste products and carbon dioxide. Any imbalance in the hemostatic and cardiovascular systems can lead to death and severe debility. A number of animals have developed mechanisms to target these systems and exploit the vulnerability. In some species (for example, snakes), such mechanisms are used to immobilize and kill the victim/prey, whereas in others (for example, insects, such as leaches, mosquitoes and ticks), they are used to provide a continuous supply of blood. These mechanisms include, but are not limited to, procoagulant and anticoagulant actions that affect the coagulation cascade and platelet aggregation, as well as altering vasodilatory responses. In all these various animals, these mechanisms have evolved to perfection over millions of years to support their survival. In last 3-4 decades, due to the efforts of scientists from various backgrounds including biology, protein chemistry, molecular biology, pharmacology, hematology, and structural biology, significant progress in understanding the structure-function relationships, as well as the mechanism of action have been made in a number of exogenous factors that affect blood coagulation, platelet aggregation and vasodilation from various animals. These exogenous factors have contributed significantly to the development of research tools as well as providing new therapeutic agents. With the increase average age of the population coupled with changes in life style in recent years, there has been a significant increase in cardiovascular and hematological disorders. Thus scientists in both academic institutions as well as the pharmaceutical industry are developing better therapeutic agents to improve the quality of life. This impetus has lead to the search for novel agents from various sources that interfere with cardiovascular and hematalogical processes. Although at first glance exogenous factors appear to function as ‘villains’, several life-saving drugs have been developed based upon these factors. Such drugs or drug leads include those that inhibit the angiotensin converting enzymes (Captopril and Enalapril), that block platelet receptors (Eptifibatide and Tirofiban), or that digest thrombotic plugs (Alfimeprase and bat plasminogen activator) to name a few. Several new and exciting success stories are currently unfolding. In this book, recent studies on some of the exogenous factors that play crucial roles in cardiovascular and hematological disorders are reviewed in order to consolidate the efforts in this area of research and to recruit new, talented researchers. The 25-30 review chapters, each written by experts in their field, compiled herein are devoted to exogenous factors affecting platelet aggregation, anticoagulant and procoagulant proteins, fibrinolytic proteins and hypotensive agents (For details see, Contents of the Book). This book is intended to help to create elevated awareness and enthusiasm in the field of exogenous factors. I believe that this book will provide greater impetus to the search for novel proteins based on naturally occurring exogenous factors. This will be the first book dealing extensively with exogenous factors in the last 25 years. The book will provide a ready reference to the different approaches used to solve complex problems in protein chemistry and pharmacology of exogenous factors. The book will update our understanding of the structure-function relationships and mechanisms of action of exogenous factors and provide great insights into future directions for solving the remaining challenges.




Venoms to Drugs


Book Description

This unique book will provide an up to date and comprehensive account of the potential of peptides and proteins from animal venoms as possible therapeutics. The pharmaceutical industry has become increasingly interested in biologics from animal venoms as a potential source for therapeutic agents in recent years, with a particularly emphasis on peptides. To date six drugs derived from venom peptides or proteins have been approved by the FDA, with nine further agents currently being investigated in clinical trials. In addition to these drugs in approved or advanced stages of development, many more peptides and proteins are being studied in varying stages of preclinical development. Topics covered include chemistry and structural biology of animal venoms, proteomic and transcriptomic approaches to drug discovery, bioassays, high-throughput screens and target identification, and reptile, scorpion, spider and cone snail venoms as a platform for drug development. Case studies are used to illustrate methods and successes and highlight issues surrounding administration and other important lessons that have been learnt from the development of approved therapeutics based on venoms. The first text to focus on this fascinating area and bridging an important gap, this book will provide the reader with essential and current knowledge on this fast-developing area. Venoms to Drugs will find wide readership with researchers working in academia and industry working in all medicinal and pharmaceutical areas.




Proteases as Targets for Therapy


Book Description

With contributions by numerous experts




Tick-Host-Pathogen Interactions


Book Description

Besides causing direct damage associated with blood feeding and in some cases through the excretion of toxins with their saliva, the main relevance of ticks lies in the wide variety of pathogens that they can transmit, including viruses, bacteria, protozoa and helminths. Owing to socioeconomic and environmental changes, tick distribution is changing with incursions of ticks and tick-borne diseases occurring in different regions of the world when the widespread deployment of chemical acaricides and repellents has led to the selection of resistance in multiple populations of ticks. New approaches that are environmentally sustainable and that provide broad protection against current and future tick-borne pathogen (TBP) are thus urgently needed. Such development, however, requires improved understanding of factors resulting in vector competence and tick-host-pathogen interactions. This Research Topic provides an overview of known molecular tick-host-pathogen interactions for a number of TBPs and highlights how this knowledge can contribute to novel control and prevention strategies for tick-borne diseases.




Aqueous Size-Exclusion Chromatography


Book Description

The rapid development of new packings for aqueous size-exclusion chromatography has revolutionized this field. High resolution non-adsorptive columns now make possible the efficient separation of proteins and the rapid and precise determination of the molecular weight distribution of synthetic polymers. This technology is also being applied to the separation of small ions, the characterization of associating systems, and the measurement of branching. At the same time, fundamental studies are elucidating the mechanisms of the various chromatographicprocesses.These developments in principles and applications are assembled for the first time in this book. Fundamental issues are dealt with: the roles of pore structure and macromolecular dimensions, hydrophobic and electrostatic effects, and the determination and control of column efficiency. High-performance packings based on derivatized silica are reviewed in detail. Special techniques are thoroughly described, including SEC/LALLS, inverse exclusion chromatography, and frontal zone chromatography. Attention is focussed on special applications of size-exclusion methods, such as the characterization of micelles, separations of inorganic ions, and Hummel-Dreyer and related methods for equilibrium systems. Protein chromatography is dealt with in both dedicated sections and throughout the book as a whole.This is a particularly comprehensive and authoritative work - all the contributions review broad topics of general significance and the authors are of high repute. The material will be of special value for the characterization of synthetic water-soluble polymers, especially polyelectrolytes. Biochemists will find fundamental and practical guidance on protein separations. Researchers confronted with solutes that exhibit complex chromatographic behavior, such as humic acids, aggregating proteins, and micelles should find the contents of this volume illuminating.




Community, Diversity, and Difference


Book Description

This book has its philosophical starting point in the idea that group-based social movements have positive implications for peace politics. It explores ways of imagining community, nation, and international systems through a political lens that is attentive to diversity and different lived experiences. Contributors suggest how groups might work toward new nonviolent conceptions and experiences of diverse communities and global stability.




Doctor Who and Philosophy


Book Description

Philosophers look at the deeper issues raised by the adventures of Doctor Who, the main character in the long-running science fiction TV series of the same name.




Biogeochemistry of Trace Elements


Book Description

Over the past few decades, tremendous progress in analytical facilities allowed for the decreasing detection limits of trace element (TE) analysis in a large number of organic and inorganic matrices. This was especially true for freshwater aquatic systems, where direct measurements of more than forty trace elements have become possible provided that necessary precautions against pollution are made and required sample preparation protocol is maintained. Therefore, analyses of both liquid (water) and solid (biomass, sediments, soils, and aerosol particles) compartments of the landscape continuum allowed for a new perspective on biogeochemical factors of trace elements in a large panel of terrestrial environments. However, among all Earth biomes, the Arctic and subarctic regions are certainly less studied from a trace element biogeochemical view point.This book adresses a variety of geochemical and biogeochemical issues of trace element behavior in soils, waters, and plants across the world, from Eastern Europe to Siberian subarctic and Arctic islands. It presents a synthesis of state-of-the-art studiesusing precise analytical techniqueson trace element concentrations, fractionation, and migration in the main biogeochemical reservoirs of the Northern Hemisphere. This book combines chapters on trace elements in soils, plants, soil waters, lakes, rivers and their estuarine zones, and atmopsheric aerosols. As such, it provides a comprehensive view of current TE biogeochemistry and can serve as a reference compilation of available information for judging future changes in trace element biogeochemistry for terrestrial environments influenced by climate warming or increasing anthropogenic pollution.