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Book Critical Role of Phosphorylated Human Lysyl tRNA Synthetase in the HIV 1 Lifecycle

Download or read book Critical Role of Phosphorylated Human Lysyl tRNA Synthetase in the HIV 1 Lifecycle written by Yingke Tang (Ph. D. in chemistry) and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Host cell tRNALys3 is selectively incorporated into HIV-1 particles and acts as the primer to initiate reverse transcription of the viral genome. Lysyl-tRNA synthetase (LysRS), the only cellular factor that specifically interacts with all tRNALys isoacceptors, is also incorporated into HIV-1 particles through interaction with HIV-1 Gag. LysRS facilitates selective incorporation of tRNALys into viral particles, a process that is important for progeny virion infectivity. A recent study reported the unexpected finding that LysRS is partially re-localized from its normal cytoplasmic location in the multi-synthetase complex (MSC) to the nucleus during HIV-1 infection. Here, we investigated the nuclear function of LysRS in HIV-1 replication. Both nuclear localization and packaging of LysRS into HIV-1 particles depend on phosphorylation of S207(pS207). This modification results in a LysRS conformational change, loss of aminoacylation activity, and release from the MSC. Using a pS207-specific antibody, we detected endogenous pS207-LysRS during single-cycle HIV-1 infection in HEK 293T, Jurkat, SupT-1 and THP-1 cell lines. Previous work showed that pS207-LysRS regulates transcription in mast cells via increased synthesis of diadenosine tetraphosphate, Ap4A, which leads to USF-2 and MITF transcription factor activation. We now show that LysRS phosphorylation also regulates HIV-1 transcription in CD4+ T cell lines. Overexpression of wild-type LysRS, but not the phosphoablative S207A mutant, activated HIV-1 LTR promoter-driven luciferase expression. We also generated a homozygous LysRS-S207A knock-in Jurkat cell line (JurkatS207A) using CRISPR-cas9. HIV-1NL4-3 replication is severely reduced in JurkatS207A, an effect that is rescued by S207D-LysRS expression, supporting a critical role for LysRS phosphorylation in the HIV-1 lifecycle. In the MSC, LysRS interacts with the N-terminal domain (N36) of the aminoacyl-tRNA synthetase–interacting multifunctional protein 2 (AIMP2). This interaction locks LysRS into an aminoacylation-competent conformation. We now show that overexpressing the AIMP2-N36 peptide blocks the nuclear relocalization of LysRS and inhibits HIV-1 replication, presumably by binding and sequestering pS207-LysRS in the cytoplasm. Transcription of HIV-1 gRNA and other USF-2 target genes was also lower in JurkatS207A cells as well as in the AIMP2-N36-expressing cells, supporting a regulatory role for LysRS in the nucleus. We showed that transfection of exogenous Ap4A promotes transcription and reactivation of HIV-1 in Jurkat cells. Thus, we propose that nuclear pS207-LysRS generates Ap4A to activate HIV-1 transcription, suggesting possible roles for LysRS in maintaining HIV-1 latency and exposing new potential targets for antiviral intervention. To investigate the effect of LysRS phosphorylation on selective packaging of non-aminoacylated tRNALys3, total viral RNA was analyzed by acidic northern blotting and RT-qPCR. Whereas over 95% of tRNAs in cells are charged, all tRNALys3 incorporated into viral particles, as well as other minor packaged tRNA species, are uncharged. tRNALys3 packaging levels are significantly decreased in LysRS knockdown cells, JurkatS207A cells and AIMP2-N36 expressing cells, supporting a key role for pS207-LysRS in tRNALys3 packaging. In summary, these studies address unanswered questions regarding the critical roles of pS207-LysRS in the HIV-1 lifecycle and provide insights into novel anti-viral strategies. In an ongoing microscopy study, we are employing several imaging methods to investigate the cellular location of tRNALys3 primer annealing. A DNA probe was designed and confirmed to specifically detect annealed tRNALys3 using fluorescence in situ hybridization (FISH). In addition, HIV-1 Gag and gRNA were visualized by immunofluorescence staining and the MS2-GFP coat protein system, respectively. Taken together, this study will reveal the cellular location of tRNALys3 annealing to the HIV-1 PBS during assembly. Recent in vitro studies identified a high-affinity DNA aptamer that bound HIV-1 reverse transcriptase (RT) with low picomolar affinity. This 38-mer aptamer folds into a hairpin and binds to RT, adopting a pre-bent conformation that mimics the structure of the template-primer complex. To investigate the anti-HIV effect of this aptamer in cells, we used a novel cell penetrating cyclic peptide (Cpp) as the vehicle to deliver the DNA aptamer into HIV-1 producer cells or infected cells. Progeny viral production and viral infectivity were significantly impaired when the producer cells were treated with low nM concentrations of the Cpp/aptamer complex. However, the Cpp/aptamer treatment only resulted in moderate inhibition of incoming HIV-1 infection, consistent with recent reports that capsid uncoating occurs in the nucleus. This study suggests an RT-targeting aptamer delivered using the Cpp approach may be a promising new anti-HIV-1 strategy.

Book Aminoacyl tRNA Synthetases in Biology and Medicine

Download or read book Aminoacyl tRNA Synthetases in Biology and Medicine written by Sunghoon Kim and published by Springer. This book was released on 2014-04-28 with total page 355 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will focus on new molecular interactions and novel activities and the associated diseases that have been recently discovered from the studies of eukaryotic and mammalian aminoacyl-tRNA synthetases. In addition, the potential applications of ARS researches in biotechnology and medicine will be addressed.

Book Index Medicus

Download or read book Index Medicus written by and published by . This book was released on 2001-08 with total page 2156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.

Book RNA protein Interactions

Download or read book RNA protein Interactions written by Kiyoshi Nagai and published by Oxford University Press, USA. This book was released on 1994 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: The study of RNA-protein interactions is crucial to understanding the mechanisms and control of gene expression and protein synthesis. The realization that RNAs are often far more biologically active than was previously appreciated has stimulated a great deal of new research in this field. Uniquely, in this book, the world's leading researchers have collaborated to produce a comprehensive and current review of RNA-protein interactions for all scientists working in this area. Timely, comprehensive, and authoritative, this new Frontiers title will be invaluable for all researchers in molecular biology, biochemistry and structural biology.

Book Biomaterials

    Book Details:
  • Author : David Byrom
  • Publisher : Springer
  • Release : 1991-06-18
  • ISBN : 1349111678
  • Pages : 356 pages

Download or read book Biomaterials written by David Byrom and published by Springer. This book was released on 1991-06-18 with total page 356 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biomaterials are produced from biological material and are used for their physical characteristics. This book looks at the range of biomaterials and their applications which range from the use of polysaccharides as thickening agents to the use of proteins as fibres and adhesives.

Book Biology of Aminoacyl tRNA Synthetases

Download or read book Biology of Aminoacyl tRNA Synthetases written by and published by Academic Press. This book was released on 2020-10-23 with total page 440 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biology of Aminoacyl-tRNA Synthetases, Volume 48 in The Enzymes series, highlights new advances in the field, with this new volume presenting interesting chapters on A narrative about our work on the endless frontier of editing, The puzzling evolution of aminoacyl-tRNA synthetases, Structural basis of the tRNA recognition by aminoacyl-tRNA synthetases, Catalytic strategies of aminoacyl-tRNA synthetases, Trans-editing by aminoacyl-tRNA synthetase-like editing domains, Adaptive and maladaptive mistranslation arising from aminoacyl-tRNA synthetases, Non-canonical inputs and outputs of tRNA aminoacylation, Structure and function of multi-tRNA synthetase complexes, Mitochondrial aminoacyl-tRNA synthetases, Non-canonical functions of human cytoplasmic tyrosyl-, tryptophanyl- and other aminoacyl-tRNA synthetases, and much more. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in The Enzymes series

Book Comprehensive Biochemistry for Dentistry

Download or read book Comprehensive Biochemistry for Dentistry written by Anil Gupta and published by Springer. This book was released on 2018-12-30 with total page 617 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book combines fundamental concepts of biochemistry and the dental sciences to provide an authentic, coherent and comprehensive text for dental students. It describes in simple language the intricate pathophysiology of biomolecules in health and in diseases of dental and oral tissues. This book also describes the evolution of biochemistry in a chronological order, provides information about the fundamental chemical structure, classification and biological significance of biomolecules, vitamins and hormones, enriched with flow charts and diagrams for easy understanding and quick reference. It includes chapters on nucleic acids, nutrition and serum enzymes and organ function tests, and offers an innovative approach to familiarize dental students with the biochemical composition of enamel, dentine, cementum and saliva, explaining the biochemical basis of dental caries, periodontal diseases, role of fluorides in caries prophylaxis, fluoride toxicity, and the role of amino acids as anti-hypersensitive agents.

Book Evidence Based Approach to Vitamins and Minerals

Download or read book Evidence Based Approach to Vitamins and Minerals written by Jane Higdon and published by Thieme. This book was released on 2011-09-07 with total page 547 pages. Available in PDF, EPUB and Kindle. Book excerpt: The latest and most accurate, peer-reviewed information on the role of vitamins and minerals in health and disease An Evidence-Based Approach to Vitamins and Minerals: Health Benefits and Intake Recommendations is a trusted resource for the health professional who needs to interpret the explosion of studies on the role of micronutrients in health and disease and who is concerned about the proliferation of dietary supplements now available to the consumer. This evidence-based reference, now in a second edition, presents the most current scientific, epidemiological and clinical research on the role of vitamins and minerals in preventing disease and promoting optimal health. Organized by micronutrient, the book covers biological function, deficiency, recommended daily allowance, role in disease prevention and treatment, sources, safety, and interactions with other micronutrients and drugs--all endorsed by the internationally acclaimed Linus Pauling Institute at Oregon State University. Special Features: Each chapter reviewed by a recognized expert in the field, who also served on the book's Editorial Advisory Board Contains the latest intake recommendations from the Linus Pauling Institute, as well as the Food and Nutrition Board of the Institute for Medicine Provides a complete index by disease or disorder that facilitates easy location of condition-specific information found in multiple chapters Extensively referenced, with hundreds of citations from the most current experimental, clinical and epidemiological studies Includes useful appendices covering drug-nutrient interactions and nutrient-nutrient interactions, a glossary of terms, a units conversion table, and the Linus Pauling Institute "Prescription for Health," summarizing its recommendations for a healthy diet, lifestyle, and supplement use Taking the approach that micronutrients play a significant role not only in preventing deficiency disease, but in enhancing general health and averting chronic disease, this book is essential for physicians, nutritionists, and allied health professionals who need the most reliable, up-to-date information in this rapidly expanding field.

Book Nanotechnology in Diagnosis  Treatment and Prophylaxis of Infectious Diseases

Download or read book Nanotechnology in Diagnosis Treatment and Prophylaxis of Infectious Diseases written by Mahendra Rai and published by Academic Press. This book was released on 2015-05-23 with total page 341 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nanotechnology in Diagnosis, Treatment and Prophylaxis of Infectious Diseases delivers comprehensive coverage of the application of nanotechnology to pressing problems in infectious disease. This text equips readers with cutting-edge knowledge of promising developments and future prospects in nanotechnology, paying special attention to microbes that are now resistant to conventional antibiotics, a concerning problem in modern medicine. Readers will find a thorough discussion of this new approach to infectious disease treatment, including the reasons nanotechnology presents a promising avenue for the diagnosis, treatment, and prophylaxis of infectious diseases. - Provides a comprehensive overview of the use of nanotechnology in the treatment and diagnosis of infectious diseases - Covers all common types of infective agents, including bacteria, viruses, fungi, and protozoa, along with their vectors, ticks, mosquitoes, flies, etc. - Delivers commentary from an international researcher base, providing insights across differing economic statuses - Includes a foundation of basic nanotechnological concepts to aid in designing new strategies to combat several pathogenic diseases and cancer - Illustrates the high antimicrobial potential of nanoparticles, ultimately demonstrating how they are a promising alternative class that can be successfully used in fighting a myriad of infections

Book Protein Nucleic Acid Interactions

Download or read book Protein Nucleic Acid Interactions written by Phoebe A. Rice and published by Royal Society of Chemistry. This book was released on 2008-05-22 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides both in-depth background and up-to-date information in this area. The chapters are organized by general themes and principles, written by experts who illustrate topics with current findings. Topics covered include: - the role of ions and hydration in protein-nucleic acid interactions - transcription factors and combinatorial specificity - indirect readout of DNA sequence - single-stranded nucleic acid binding proteins - nucleic acid junctions and proteins, - RNA protein recognition - recognition of DNA damage. It will be a key reference for both advanced students and established scientists wishing to broaden their horizons.

Book Model Organisms for Microbial Pathogenesis  Biofilm Formation and Antimicrobial Drug Discovery

Download or read book Model Organisms for Microbial Pathogenesis Biofilm Formation and Antimicrobial Drug Discovery written by Busi Siddhardha and published by Springer Nature. This book was released on 2020-03-28 with total page 685 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides essential insights into microbial pathogenesis, host-pathogen interactions, and the anti-microbial drug resistance of various human pathogens on the basis of various model organisms. The initial sections of the book introduce readers to the mechanisms of microbial pathogenesis, host-pathogen interactions, anti-microbial drug resistance, and the dynamics of biofilm formation. Due to the emergence of various microbial resistant strains, it is especially important to understand the prognosis for microbial infections, disease progression profiles, and mechanisms of resistance to antibiotic therapy in order to develop novel therapeutic strategies. In turn, the second part of the book presents a comparative analysis of various animal models to help readers understand microbial pathogenesis, host-pathogen interactions, anti-microbial drug discovery, anti-biofilm therapeutics, and treatment regimes. Given its scope, the book represents a valuable asset for microbiologists, biotechnologists, medical professionals, drug development researchers, and pharmacologists alike.

Book Genome Mapping and Genomics in Animal Associated Microbes

Download or read book Genome Mapping and Genomics in Animal Associated Microbes written by Vishvanath Nene and published by Springer Science & Business Media. This book was released on 2008-11-24 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: Achievements and progress in genome mapping and the genomics of microbes supersede by far those for higher plants and animals, in part due to their enormous economic implication but also smaller genome size. In the post-genomic era, whole genome sequences of animal-associated microbes are providing clues to depicting the genetic basis of the complex host-pathogen relationships and the evolution of parasitism; and to improving methods of controlling pathogens. This volume focuses on a globally important group of intracellular prokaryotic pathogens which affect livestock animals. These include Brucella, Mycobacterium, Anaplasma and Ehrlichia, as well as the protozoan pathogens Cryptosporidium and Theileria, for which genome sequence data is available. Insights from comparative genomics of the microbes described provide clues to the adaptation involved in host-microbe interactions, as well as resources potentially useful for application in future research and product development.

Book TRNA

Download or read book TRNA written by Dieter Söll and published by . This book was released on 1995 with total page 572 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Principles of Human Nutrition

Download or read book Principles of Human Nutrition written by Martin Eastwood and published by John Wiley & Sons. This book was released on 2013-06-05 with total page 1088 pages. Available in PDF, EPUB and Kindle. Book excerpt: This exciting new book is the updated and revised second edition of an extremely popular and well-received textbook. Written by Martin Eastwood, well respected internationally in nutritional sciences, this important new edition provides students with a thorough book that should be adopted for course use on many courses worldwide. Taking into account constructive comments received by students and teachers who used and enjoyed the first edition, this new edition retains the original freshness of the 1st edition, looking at nutrition as an exciting discipline. Special features within the book to help students include summaries, boxes and questions. Carefully laid out to assist learning, the book is divided broadly into sections, providing in-depth coverage of the following subjects: food in the community metabolism of nutrients by an individual, dictated by genetic makeup, measurement of an individual’s nutritional status essential, non-essential and non-nutrients; their selection, ingestion, digestion, absorption and metabolism nutritional requirements in the normal individual and for specific diseases Principles of Human Nutrition, 2nd Edition is primarily written as a course text for those studying degree courses in nutrition and dietetics and for students on modular courses on nutrition within other degree courses, e.g. food studies, medicine, health sciences, nursing and biological sciences. It is also of great value as a reference for professional nutritionists and dietitians, food scientists and health professionals based in academia, in practice and in commercial positions such as within the food and pharmaceutical industries. Multiple copies of this valuable book should also be on the shelves of all universities, medical schools and research establishments where these subjects are studied and taught. For supplementary material associated with this textbook and its contents, please visit the web pages for this book, on the publishers’ website: http://www.blackwellpublishing.com/eastwood/ Martin Eastwood was formerly consultant gastroenterologist at the Western General Hospital, Edinburgh, U. K. and Reader in Medicine at the University of Edinburgh, U. K.

Book Chromatin Signaling and Diseases

Download or read book Chromatin Signaling and Diseases written by Olivier Binda and published by Academic Press. This book was released on 2016-08-06 with total page 468 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chromatin Signaling and Diseases covers the molecular mechanisms that regulate gene expression, which govern everything from embryonic development, growth, and human pathologies associated with aging, such as cancer. This book helps researchers learn about or keep up with the quickly expanding field of chromatin signaling. After reading this book, clinicians will be more capable of explaining the mechanisms of gene expression regulation to their patients to reassure them about new drug developments that target chromatin signaling mechanisms. For example, several epigenetic drugs that act on chromatin signaling factors are in clinical trials or even approved for usage in cancer treatments, Alzheimer's, and Huntington's diseases. Other epigenetic drugs are in development to regulate various class of chromatin signaling factors. To keep up with this changing landscape, clinicians and doctors will need to stay familiar with genetic advances that translate to clinical practice, such as chromatin signaling. Although sequencing of the human genome was completed over a decade ago and its structure investigated for nearly half a century, molecular mechanisms that regulate gene expression remain largely misunderstood. An emerging concept called chromatin signaling proposes that small protein domains recognize chemical modifications on the genome scaffolding histone proteins, facilitating the nucleation of enzymatic complexes at specific loci that then open up or shut down the access to genetic information, thereby regulating gene expression. The addition and removal of chemical modifications on histones, as well as the proteins that specifically recognize these, is reviewed in Chromatin Signaling and Diseases. Finally, the impact of gene expression defects associated with malfunctioning chromatin signaling is also explored. - Explains molecular mechanisms that regulate gene expression, which governs everything from embryonic development, growth, and human pathologies associated with aging - Educates clinicians and researchers about chromatin signaling, a molecular mechanism that is changing our understanding of human pathology - Explores the addition and removal of chemical modifications on histones, the proteins that specifically recognize these, and the impact of gene expression defects associated with malfunctioning chromatin signaling - Helps researchers learn about the quickly expanding field of chromatin signaling

Book Cavernous Malformations

Download or read book Cavernous Malformations written by Issam A. Awad and published by Thieme. This book was released on 1993 with total page 250 pages. Available in PDF, EPUB and Kindle. Book excerpt: The massive convergence of information about cavernous malformations has been synthesized in this volume by experts in the field of pathology, neuroradiology and neurosurgery. Cavernous Malformations represents state-of-the-art knowledge about this lesion and the spectrum of opinion about its nature, clinical behavior and management strategies. Highlights of Cavernous Malformations: Definition and pathologic features Epidemiology Diagnostic imaging Epilepsy Hemorrhage Conservative management Surgical intervention Microsurgical treatments Spinal cavernous malformations Pediatrics Radiotherapy (Distributed by Thieme for the American Association of Neurological Surgeons)

Book Viral Pathogenesis

    Book Details:
  • Author : Michael G. Katze
  • Publisher : Academic Press
  • Release : 2015-12-30
  • ISBN : 0128011742
  • Pages : 368 pages

Download or read book Viral Pathogenesis written by Michael G. Katze and published by Academic Press. This book was released on 2015-12-30 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral Pathogenesis: From Basics to Systems Biology, Third Edition, has been thoroughly updated to cover topical advances in the evolving field of viral pathogenesis, while also providing the requisite classic foundational information for which it is recognized. The book provides key coverage of the newfound ability to profile molecular events on a system-wide scale, which has led to a deeper understanding of virus-host interactions, host signaling and molecular-interaction networks, and the role of host genetics in determining disease outcome. In addition, the content has been augmented with short chapters on seminal breakthroughs and profiles of their progenitors, as well as short commentaries on important or controversial issues in the field. Thus, the reader will be given a view of virology research with perspectives on issues such as biomedical ethics, public health policy, and human health. In summary, the third edition will give the student a sense of the exciting new perspectives on viral pathogenesis that have been provided by recent developments in genomics, computation, modeling, and systems biology. - Covers all aspects of viral infection, including viral entry, replication, and release, as well as innate and adaptive immunity and viral pathogenesis - Provides a fresh perspective on the approaches used to understand how viruses cause disease - Features molecular profiling techniques, whole genome sequencing, and innovative computational methods - Highlights the use of contemporary approaches and the insights they provide to the field