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Book Elucidation of a Proteolytic Mechanism Required for Kaposi s Sarcoma associated Herpesvirus Replication

Download or read book Elucidation of a Proteolytic Mechanism Required for Kaposi s Sarcoma associated Herpesvirus Replication written by Alan Brown Marnett and published by . This book was released on 2005 with total page 374 pages. Available in PDF, EPUB and Kindle. Book excerpt: Herpesviruses represent one of the most prevalent human pathogens worldwide. Infection results in a number of diseases ranging from cold sores to cancer. Yet despite the large clinical variation in disease states, the proteins expressed during the lytic cycle of all herpesviruses are highly conserved. A maturational serine protease is expressed late in viral replication and is required for production of properly assembled infectious progeny. In vitro structural and functional analysis has revealed the enzyme possesses a novel protein fold and is activated by dimerization. However, the mechanism of regulation of the enzyme both at a molecular level and in the context of viral replication is unknown. Positional scanning synthetic combinatorial libraries were used to define the substrate specificity of the protease encoded by Kaposi's Sarcoma-associated herpesvirus (KSHV). The strict specificity observed was used to guide the design and synthesis of a peptidyl-diphenylphosphonate inhibitor targeting the active site of the enzyme. Covalent modification of the active site serine of the enzyme by the transition-state analog inhibitor dramatically shifted the equilibrium toward dimeric enzyme illustrating the intimate communication between the spatially separate active sites and dimer interface of the protease. To elucidate the mechanism of stabilization and activation during catalysis, structural analysis was performed on purely monomeric (M197D), purely dimeric (inhibited) and an equilibrium mixture (uninhibited wild-type) by circular dichroism and nuclear magnetic resonance. A massive conformational change was observed upon loss of dimerization in which helices 5 and 6, at the interface and active site, respectively, become disordered, which destabilizes essential catalytic components. A disulfide bond was engineered into the protease at helix 6 that prevented the conformational change and subsequent inactivation of the enzyme. Addition of oxidant or reductant reversibly recovered or abolished enzymatic activity, respectively, even in a monomeric variant of the protease. A reduction in viral replication similar to currently available therapies targeting the viral polymerase was observed upon treatment of reactivated KSHV with the protease inhibitor. The work not only validated the virally-encoded protease as a potential therapeutic target, but also presented a mechanism by which protease inhibition may occur in vivo .

Book Human Herpesviruses

    Book Details:
  • Author : Ann Arvin
  • Publisher : Cambridge University Press
  • Release : 2007-08-16
  • ISBN : 1139461648
  • Pages : 1325 pages

Download or read book Human Herpesviruses written by Ann Arvin and published by Cambridge University Press. This book was released on 2007-08-16 with total page 1325 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.

Book Dissertation Abstracts International

Download or read book Dissertation Abstracts International written by and published by . This book was released on 2005 with total page 918 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Recoding  Expansion of Decoding Rules Enriches Gene Expression

Download or read book Recoding Expansion of Decoding Rules Enriches Gene Expression written by John F. Atkins and published by Springer Science & Business Media. This book was released on 2010-03-10 with total page 473 pages. Available in PDF, EPUB and Kindle. Book excerpt: The literature on recoding is scattered, so this superb book ?lls a need by prov- ing up-to-date, comprehensive, authoritative reviews of the many kinds of recoding phenomena. Between 1961 and 1966 my colleagues and I deciphered the genetic code in Escherichia coli and showed that the genetic code is the same in E. coli, Xenopus laevis, and guinea pig tissues. These results showed that the code has been c- served during evolution and strongly suggested that the code appeared very early during biological evolution, that all forms of life on earth descended from a c- mon ancestor, and thus that all forms of life on this planet are related to one another. The problem of biological time was solved by encoding information in DNA and retrieving the information for each new generation, for it is easier to make a new organism than it is to repair an aging, malfunctioning one. Subsequently, small modi?cations of the standard genetic code were found in certain organisms and in mitochondria. Mitochondrial DNA only encodes about 10–13 proteins, so some modi?cations of the genetic code are tolerated that pr- ably would be lethal if applied to the thousands of kinds of proteins encoded by genomic DNA.

Book Human Herpesviruses

    Book Details:
  • Author : Yasushi Kawaguchi
  • Publisher : Springer
  • Release : 2018-06-12
  • ISBN : 9811072302
  • Pages : 498 pages

Download or read book Human Herpesviruses written by Yasushi Kawaguchi and published by Springer. This book was released on 2018-06-12 with total page 498 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book introduces and reviews several topics for each human herpesvirus. One of the most important features of the book is that it covers aspects of both basic research and clinical medicine. Herpesviridae, a family of double-strand DNA viruses, has unique biological features by which these viruses establish latency after primary infection and reactivate in later life. Nine human herpesviruses are known so far, and each of them causes a variety of diseases in both primary infection and reactivation. Since the discovery of each human herpesvirus, an abundance of findings related to them has accumulated in basic research and clinical medicine. However, the vast majority of biological features is still masked in mystery. Furthermore, a strategy of treatment and prevention has not yet been established for most human herpesviruses. A wide range of readers will be interested in this volume with its treatment of problematic points and latest findings in the field.

Book Heparanase

    Book Details:
  • Author : Israel Vlodavsky
  • Publisher : Springer Nature
  • Release : 2020-04-09
  • ISBN : 3030345211
  • Pages : 871 pages

Download or read book Heparanase written by Israel Vlodavsky and published by Springer Nature. This book was released on 2020-04-09 with total page 871 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by internationally recognized leaders in Heparanase biology, the book’s eight chapters offer an opportunity for scientists, clinicians and advanced students in cell biology, tumor biology and oncology to obtain a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications. Proteases and their involvement in cancer progression have been well addressed and documented; however, the emerging premise presented within this book is that Heparanase is a master regulator of aggressive cancer phenotypes and crosstalk with the tumor microenvironment. This endoglycosidase contributes to tumor-mediated remodeling of the extracellular matrix and cell surfaces, augmenting the bioavailability of pro-tumorigenic and pro-inflammatory growth factors and cytokines that are bound to Heparan sulfate. Compelling evidence ties Heparanase with all steps of tumor progression including tumor initiation, growth, angiogenesis, metastasis, and chemoresistance, supporting the notion that Heparanase is an important contributor to the poor outcome of cancer patients and a validated target for therapy. Unlike Heparanase, heparanase-2, a close homolog of Heparanase, lacks enzymatic activity, inhibits Heparanase, and regulates selected genes that promote normal differentiation and tumor suppression. Written by internationally recognized leaders in Heparanase biology, this volume presents a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications to scientists, clinicians and advanced students in cell biology, tumor biology and oncology.

Book The Unfolded Protein Response

Download or read book The Unfolded Protein Response written by Roberto Pérez Torrado and published by . This book was released on 2022 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume is divided in six section covering the most experimental approaches involved in the study of the unfolded protein response (UPR) pathway. Chapters detail determination of unfolded protein levels, methods to study UPR signal transmission, analysing the outcomes of the UPR pathway activation, UPR studies in mammalian models, UPR in alternative models, and UPR and disease. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, The Unfolded Protein Response: Methods and Protocols aims to describe key methods and approaches used in the study of the UPR pathway and its complex cellular implications. Chapter 6 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Book The Mechanisms of DNA Replication

Download or read book The Mechanisms of DNA Replication written by David Stuart and published by BoD – Books on Demand. This book was released on 2013-02-20 with total page 502 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA replication is a fundamental part of the life cycle of all organisms. Not surprisingly many aspects of this process display profound conservation across organisms in all domains of life. The chapters in this volume outline and review the current state of knowledge on several key aspects of the DNA replication process. This is a critical process in both normal growth and development and in relation to a broad variety of pathological conditions including cancer. The reader will be provided with new insights into the initiation, regulation, and progression of DNA replication as well as a collection of thought provoking questions and summaries to direct future investigations.

Book Viral Oncology

    Book Details:
  • Author : George Klein
  • Publisher :
  • Release : 1980
  • ISBN :
  • Pages : 874 pages

Download or read book Viral Oncology written by George Klein and published by . This book was released on 1980 with total page 874 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Epigenetics of Infectious Diseases

Download or read book Epigenetics of Infectious Diseases written by Walter Doerfler and published by Springer. This book was released on 2017-05-26 with total page 281 pages. Available in PDF, EPUB and Kindle. Book excerpt: The present volume of Epigenetics and Human Health is devoted to the patho-epigenetics of viral and microbial infections, an exiting new field of disease-related epigenetic research. As recognized during the past years, epigenetic reprogramming of pathogen and host genome functions – the latter frequently induced by pathogens – plays an important role in many infectious processes. Beyond their immediate relevance for pathogen proliferation and obligatorily associated symptoms, such alterations frequently contribute to severe additional complications, such as the development of immunodeficiency, cancer and various chronic disorders. This holds in particular for epigenetic dysregulation of host gene expression induced by latent infections. The present book summarizes current knowledge of the mechanisms underlying epigenetic changes caused by viral, bacterial, fungal and protozoan infections and their impact on human health.

Book Fenner and White s Medical Virology

Download or read book Fenner and White s Medical Virology written by Christopher J. Burrell and published by Academic Press. This book was released on 2016-11-09 with total page 604 pages. Available in PDF, EPUB and Kindle. Book excerpt: Fenner and White's Medical Virology, Fifth Edition provides an integrated view of related sciences, from cell biology, to medical epidemiology and human social behavior. The perspective represented by this book, that of medical virology as an infectious disease science, is meant to provide a starting point, an anchor, for those who must relate the subject to clinical practice, public health practice, scholarly research, and other endeavors. The book presents detailed exposition on the properties of viruses, how viruses replicate, and how viruses cause disease. These chapters are then followed by an overview of the principles of diagnosis, epidemiology, and how virus infections can be controlled. The first section concludes with a discussion on emergence and attempts to predict the next major public health challenges. These form a guide for delving into the specific diseases of interest to the reader as described in Part II. This lucid and concise, yet comprehensive, text is admirably suited to the needs of not only advanced students of science and medicine, but also postgraduate students, teachers, and research workers in all areas of virology. Features updated and expanded coverage of pathogenesis and immunity Contains the latest laboratory diagnostic methods Provides insights into clinical features of human viral disease, vaccines, chemotherapy, epidemiology, and control

Book Leong s Manual of Diagnostic Antibodies for Immunohistology

Download or read book Leong s Manual of Diagnostic Antibodies for Immunohistology written by Runjan Chetty and published by Cambridge University Press. This book was released on 2016-11-28 with total page 525 pages. Available in PDF, EPUB and Kindle. Book excerpt: Providing a unique A-Z guide to antibodies for immunohistology, this is an indispensable source for pathologists to ensure the correct application of immunohistochemistry in daily practice. Each entry includes commercial sources, clones, descriptions of stained proteins/epitopes, the full staining spectrum of normal and tumor tissues, staining pattern and cellular localization, the range of conditions of immunoreactivity, and pitfalls of the antibody's immunoprofile, giving pathologists a truly thorough quick-reference guide to sources, preparation and applications of specific antibodies. Appendices provide useful quick-reference tables of antibody panels for differential diagnoses, as well as summaries of diagnostic applications. Expanded from previous editions with over forty new entries, this handbook for diagnostic, therapeutic, prognostic and research applications of antibodies is an essential desktop book for practicing pathologists as well as researchers, residents and trainees.

Book Emerging Transplant Infections

Download or read book Emerging Transplant Infections written by Michele I. Morris and published by Springer. This book was released on 2021-06-22 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of transplant medicine has evolved significantly since the first kidney transplant was performed in 1954. Innovations in transplant immunosuppression have lowered the risk of organ rejection so that infectious complications are now the leading cause of hospitalization and mortality after solid organ transplant. Infection is also cited as the leading cause of non-relapse mortality after stem cell transplantation. As transplant centers have recognized the importance of transplant specific expertise in patient outcomes, the field of transplant infectious diseases has expanded into a recognized and highly valued subspecialty. International growth in solid organ and stem cell transplantation has outpaced access to such expertise, with some centers employing microbiology laboratory directors and transplant nephrologists as their lead infectious diseases consultants. This has been a particular challenge as the use of novel immunosuppressive regimens in new geographic and immigrant populations have fueled the emergence of new infection syndromes, with the initial presentation sometimes occurring in this most vulnerable patient population. This digital-first book is designed to meet the needs of practitioners engaged in transplant infectious disease practice who need more depth than they are able to find in UpToDate. It provides an overview of emerging infectious disease challenges with clinically relevant information regarding the epidemiology, diagnosis, management, and prevention of infections in solid organ and stem cell transplant recipients. Each chapter focuses on a clinical syndrome or pathogen with new or emerging implications for transplant patients. Given the rapidly evolving nature of emerging infections and topics in transplant infections, no resource has been published on these increasingly notorious issues; this this text is written by top, global experts who regularly update the material to ensure that readers will always have access to the most cutting edge material available. The editorial team consists of three experienced leaders in the field, all of whom have a strong record of scholarship and publication, as well as an international reputation. All three have focused their academic careers on emerging infectious diseases in transplantation, including a current and a past president of various infectious diseases and transplantation societies. The editors are also experienced reviewers and authors who have collaborated on multiple previous projects. All are committed to this project as a unique opportunity to make an important contribution to their field.

Book Oral Health in America

Download or read book Oral Health in America written by and published by . This book was released on 2000 with total page 32 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Molecular Virology of Human Pathogenic Viruses

Download or read book Molecular Virology of Human Pathogenic Viruses written by Wang-Shick Ryu and published by Academic Press. This book was released on 2016-03-30 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Virology of Human Pathogenic Viruses presents robust coverage of the key principles of molecular virology while emphasizing virus family structure and providing key context points for topical advances in the field. The book is organized in a logical manner to aid in student discoverability and comprehension and is based on the author’s more than 20 years of teaching experience. Each chapter will describe the viral life cycle covering the order of classification, virion and genome structure, viral proteins, life cycle, and the effect on host and an emphasis on virus-host interaction is conveyed throughout the text. Molecular Virology of Human Pathogenic Viruses provides essential information for students and professionals in virology, molecular biology, microbiology, infectious disease, and immunology and contains outstanding features such as study questions and recommended journal articles with perspectives at the end of each chapter to assist students with scientific inquiries and in reading primary literature. Presents viruses within their family structure Contains recommended journal articles with perspectives to put primary literature in context Includes integrated recommended reading references within each chapter Provides access to online ancillary package inclusive of annotated PowerPoint images, instructor’s manual, study guide, and test bank

Book New Frontiers in Organoselenium Compounds

Download or read book New Frontiers in Organoselenium Compounds written by Eder João Lenardão and published by Springer. This book was released on 2018-06-29 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents recent advances in and perspectives on the use of organoselenium compounds, primarily highlighting the new frontiers in the field of Green Chemistry, their therapeutic and biological relevance and new materials. Throughout its 200 pages, readers will find an updated and comprehensive review of new aspects of organoselenium chemistry and biochemistry. Fully referenced and written in an easy to read style, it offers readers a primary resource for including organoselenium derivatives in their projects. This book will be of interest to specialists, students and researchers involved in a broad range of fields, from synthetic green chemistry to medicinal chemistry and the chemistry of natural products. The connection between organoselenium compounds and green chemistry, despite having only recently emerged, is one of the subjects of this book. The first chapter highlights the use of Se-containing molecules as reagents and catalysts in new green protocols to access important organic transformations. The book provides a wealth of examples of bioactive Se-containing molecules, especially focusing on those with potential therapeutic uses. The second chapter focuses on the state of the art concerning the role of organoselenium compounds as antioxidants, GPx mimics, and derivatives endowed with different bioactive properties. “Organoselenium in nature” is the title of the third chapter, which equips readers with essential information on the main natural organoselenium compounds and where they are found. Selected aspects of the metabolism of selenium in plants and microorganisms are also discussed. In closing, the book includes a chapter dedicated to recent advances concerning the nonbonding interactions between organochalcogen compounds. This is currently a hot topic in selenium chemistry and biochemistry, and here readers will find key insights into the chalcogen bond and its role in the biological activity of organoselenium compounds.

Book Viral Infection and Apoptosis

Download or read book Viral Infection and Apoptosis written by and published by Mdpi AG. This book was released on 2018-01-11 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt: Apoptosis is a form of programmed cell death that enables the removal of damaged, infected, or otherwise unwanted cells in a controlled manner. Apoptosis can be initiated by multiple independent pathways that ultimately converge at a point where proteolytic enzymes belonging to the caspase family are activated, which dismantle the apoptotic cell. Multicellular organism have employed apoptotic mechanisms during host defence in response to viral infection to limit or prevent viral spread and replication. Consequently, viruses have evolved sophisticated molecular countermeasures to disarm host apoptotic defences, and this series of reviews and primary research articles in this Special Issue explores the intricate molecular interplay between viruses and their hosts when they battle for control of host apoptotic check-points.