Download or read book Analysis of the Mismatch Repair System and the Drug Resistance Phenotype of Plasmodium Falciparum written by Susan M. Thomas and published by . This book was released on 2002 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book DNA Mismatch Repair in Plasmodium Falciparum written by Meryl A. Castellini and published by . This book was released on 2010 with total page 268 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium falciparum, the causative agent of the most lethal strain of human malaria, presents an enormous public health threat due to its ability to rapidly develop resistance to current antimalarial treatment. This accelerated resistance to multiple drugs, or ARMD phenotype, is widely documented, however the molecular mechanisms that govern it are poorly understood. There is much precedence, both in human cancers and in bacterial systems, to implicate the DNA mismatch repair pathway in the parasite's dramatic ability to quickly develop resistance to a multitude of antimalarials. DNA mismatch repair (MMR) is responsible for repairing mismatched bases that arise from replication, recombination, or DNA damaging agents and facilitates genomic fidelity by a thousand fold. Mutations in MMR genes have been linked to cancer, microsatellite instability, and chemotherapeutic drug resistance. Loss of mismatch repair is most commonly associated with drug resistance due to the rapid development of advantageous point mutations. In fact, there are several examples of P. falciparum drug resistance that can be traced directly back to one point mutation in a single gene. Among these examples are resistance to chloroquine and pyrimethamine, which can be traced to point mutations in the Pfcrt and Pfdhfr genes, respectively. While P. falciparum contains most key gene homologs required for mismatch repair, the actual repair efficiency of the parasite and how it correlates with drug resistance remain unexplored. We propose that drug resistanc parasited have defective mismatch repair and that this defect has lent P. falciparum a mechanism for the development of advantageous point mutations. These parasites would then be selected for when placed under drug pressure. Using a versatile genetic assay, we established that drug sensitive HB3 parasites possess proficient, bi-directional mismatch repair. We also determined that the multiple drug resistanc, ARMD parasites W2 and Dd2 have defective DNA mismatch repair activity. Dd2 was deficient in both 3' and 5' nick directed mismatch repair. The W2 strain demonstrated the absence of 3' nick directed MMR, but was proficient on 5' nicked substrates. This repair bias is attributable to the loss of a key mismatch repair protein, MLH1, which is known to be critical for 3' nick directed MMR. To our knowledge, these studies represent the first quantification of mismatch repair activity in P. falciparum and we now hope to begin to gain new insight on the mechanisms by which the malaria parasite quickly develops resistance to current antimalarial drugs.
Download or read book American Doctoral Dissertations written by and published by . This book was released on 2001 with total page 776 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Multi Drug Resistance in Cancer written by Jun Zhou and published by Humana Press. This book was released on 2012-08-09 with total page 492 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chemotherapy is one of the major treatment options for cancer patients; however, the efficacy of chemotherapeutic management of cancer is severely limited by multidrug resistance, in that cancer cells become simultaneously resistant to many structurally and mechanistically unrelated drugs. In the past three decades, a number of mechanisms by which cancer cells acquire multidrug resistance have been discovered. In addition, the development of agents or strategies to overcome resistance has been the subject of intense study. This book contains comprehensive and up-to-date reviews of multidrug resistance mechanisms, from over-expression of ATP-binding cassette drug transporters such as P-glycoprotein, multidrug resistance-associated proteins, and breast cancer resistance p- tein to the drug ratio-dependent antagonism and the paradigm of cancer stem cells. The book also includes strategies to overcome multidrug resistance, from the development of compounds that inhibit drug transporter function to the modulation of transporter expression. In addition, this book contains techniques for the detection and imaging of drug transporters, methods for the investigation of drug resistance in animal models, and strategies to evaluate the efficacy of resistance reversal agents. The book intends to provide a state-of-the-art collection of reviews and methods for both basic and clinician investigators who are interested in cancer multidrug resistance mechanisms and reversal strategies. Tianjin, China Jun Zhou v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1 Multidrug Resistance in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bruce C. Baguley 2 Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets . . . . . . . . . . . . . . . . . . . . . . . . . .
Download or read book Cumulated Index Medicus written by and published by . This book was released on 2000 with total page 1844 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Index Medicus written by and published by . This book was released on 2004 with total page 1940 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.
Download or read book Dissertation Abstracts International written by and published by . This book was released on 2006 with total page 860 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Resistance of Malaria Parasites to Drugs written by World Health Organization. Scientific Group on Resistance of Malaria Parasites to Drugs and published by . This book was released on 1965 with total page 76 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Science and Applications of Synthetic and Systems Biology written by Institute of Medicine and published by National Academies Press. This book was released on 2011-12-30 with total page 570 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many potential applications of synthetic and systems biology are relevant to the challenges associated with the detection, surveillance, and responses to emerging and re-emerging infectious diseases. On March 14 and 15, 2011, the Institute of Medicine's (IOM's) Forum on Microbial Threats convened a public workshop in Washington, DC, to explore the current state of the science of synthetic biology, including its dependency on systems biology; discussed the different approaches that scientists are taking to engineer, or reengineer, biological systems; and discussed how the tools and approaches of synthetic and systems biology were being applied to mitigate the risks associated with emerging infectious diseases. The Science and Applications of Synthetic and Systems Biology is organized into sections as a topic-by-topic distillation of the presentations and discussions that took place at the workshop. Its purpose is to present information from relevant experience, to delineate a range of pivotal issues and their respective challenges, and to offer differing perspectives on the topic as discussed and described by the workshop participants. This report also includes a collection of individually authored papers and commentary.
Download or read book Gene Drives on the Horizon written by National Academies of Sciences, Engineering, and Medicine and published by National Academies Press. This book was released on 2016-08-28 with total page 231 pages. Available in PDF, EPUB and Kindle. Book excerpt: Research on gene drive systems is rapidly advancing. Many proposed applications of gene drive research aim to solve environmental and public health challenges, including the reduction of poverty and the burden of vector-borne diseases, such as malaria and dengue, which disproportionately impact low and middle income countries. However, due to their intrinsic qualities of rapid spread and irreversibility, gene drive systems raise many questions with respect to their safety relative to public and environmental health. Because gene drive systems are designed to alter the environments we share in ways that will be hard to anticipate and impossible to completely roll back, questions about the ethics surrounding use of this research are complex and will require very careful exploration. Gene Drives on the Horizon outlines the state of knowledge relative to the science, ethics, public engagement, and risk assessment as they pertain to research directions of gene drive systems and governance of the research process. This report offers principles for responsible practices of gene drive research and related applications for use by investigators, their institutions, the research funders, and regulators.
Download or read book The Malaria Genome Projects written by Irwin W. Sherman and published by World Scientific. This book was released on 2012 with total page 389 pages. Available in PDF, EPUB and Kindle. Book excerpt: The year 2012 marks the tenth anniversary of the announcement of the genome sequence of the human malaria parasite Plasmodium falciparum and that of its mosquito vector Anopheles. The genome sequences were a result of the Plasmodium falciparum Genome Project. This book covers in detail the biology of malaria parasites and the mosquitoes that transmit the disease, how the Genome Project came into being, the people who created it, and the cadre of scientists who are attempting to see the promise of the Project realized. The promise was: a more complete understanding of the genes of the parasite (and its vector) would provide a rational basis for the development of antimalarial drugs and vaccines, allow a better understanding of the regulation of the complex life cycle in the red blood and liver cells of the human, identify the genes the parasite uses to thwart the host immune response and the ways in which the parasite evades cure by drug treatments, as well as leading to more effective measures of control transmission. The hope was that cracking the genetic code of Plasmodium and Anopheles would reveal the biochemical Achilles heel of the parasite and its vector, leading to the development of novel drugs and better methods of control, and by finding the targets of protective immunity could result in the manufacture of effective vaccines. Through a historic approach, this book will allow for those new to the field, or those with insufficient background in the sciences, to have an easier entry point. Even scientists already working in the field may better appreciate how discoveries made in the past can impact the direction of future research.
Download or read book Stress Induced Mutagenesis written by David Mittelman and published by Springer Science & Business Media. This book was released on 2013-03-12 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt: The discovery of stress-induced mutagenesis has changed ideas about mutation and evolution, and revealed mutagenic programs that differ from standard spontaneous mutagenesis in rapidly proliferating cells. The stress-induced mutations occur during growth-limiting stress, and can include adaptive mutations that allow growth in the otherwise growth-limiting environment. The stress responses increase mutagenesis specifically when cells are maladapted to their environments, i.e. are stressed, potentially accelerating evolution then. The mutation mechanism also includes temporary suspension of post-synthesis mismatch repair, resembling mutagenesis characteristic of some cancers. Stress-induced mutation mechanisms may provide important models for genome instability underlying some cancers and genetic diseases, resistance to chemotherapeutic and antibiotic drugs, pathogenicity of microbes, and many other important evolutionary processes. This book covers pathways of stress-induced mutagenesis in all systems. The principle focus is mammalian systems, but much of what is known of these pathways comes from non-mammalian systems.
Download or read book World Malaria Report 2014 written by World Health Organization and published by World Health Organization. This book was released on 2015-07-07 with total page 241 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World malaria report 2014 summarizes information received from 97 malaria endemic countries and other sources and updates the analyses presented in 2013. It assesses global and regional malaria trends highlights progress made towards global targets and describes opportunities and challenges in controlling and eliminating the disease. Most of the data presented in this report are for 2013.
Download or read book Quasispecies Concept and Implications for Virology written by Esteban Domingo and published by Springer Science & Business Media. This book was released on 2006-02-19 with total page 413 pages. Available in PDF, EPUB and Kindle. Book excerpt: Continuous genetic variation and selection of virus subpopulations in the course of RNA virus replications are intimately related to viral disease mechanisms. The central topics of this volume are the origins of the quasispecies concept, and the implications of quasispecies dynamics for viral populations.
Download or read book Molecular Evolution written by Roderick D.M. Page and published by John Wiley & Sons. This book was released on 2009-07-14 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: The study of evolution at the molecular level has given the subject of evolutionary biology a new significance. Phylogenetic 'trees' of gene sequences are a powerful tool for recovering evolutionary relationships among species, and can be used to answer a broad range of evolutionary and ecological questions. They are also beginning to permeate the medical sciences. In this book, the authors approach the study of molecular evolution with the phylogenetic tree as a central metaphor. This will equip students and professionals with the ability to see both the evolutionary relevance of molecular data, and the significance evolutionary theory has for molecular studies. The book is accessible yet sufficiently detailed and explicit so that the student can learn the mechanics of the procedures discussed. The book is intended for senior undergraduate and graduate students taking courses in molecular evolution/phylogenetic reconstruction. It will also be a useful supplement for students taking wider courses in evolution, as well as a valuable resource for professionals. First student textbook of phylogenetic reconstruction which uses the tree as a central metaphor of evolution. Chapter summaries and annotated suggestions for further reading. Worked examples facilitate understanding of some of the more complex issues. Emphasis on clarity and accessibility.
Download or read book Antibiotic Discovery and Development written by Thomas J. Dougherty and published by Springer Science & Business Media. This book was released on 2011-12-18 with total page 1119 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume covers all aspects of the antibiotic discovery and development process through Phase II/III. The contributors, a group of highly experienced individuals in both academics and industry, include chapters on the need for new antibiotic compounds, strategies for screening for new antibiotics, sources of novel synthetic and natural antibiotics, discovery phases of lead development and optimization, and candidate compound nominations into development. Beyond discovery , the handbook will cover all of the studies to prepare for IND submission: Phase I (safety and dose ranging), progression to Phase II (efficacy), and Phase III (capturing desired initial indications). This book walks the reader through all aspects of the process, which has never been done before in a single reference. With the rise of antibiotic resistance and the increasing view that a crisis may be looming in infectious diseases, there are strong signs of renewed emphasis in antibiotic research. The purpose of the handbook is to offer a detailed overview of all aspects of the problem posed by antibiotic discovery and development.
Download or read book Bacterial Resistance to Antibiotics written by Boyan B. Bonev and published by John Wiley & Sons. This book was released on 2019-06-10 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt: AN AUTHORITATIVE SURVEY OF CURRENT RESEARCH INTO CLINICALLY USEFUL CONVENTIONAL AND NONCONVENTIONAL ANTIBIOTIC THERAPEUTICS Pharmaceutically-active antibiotics revolutionized the treatment of infectious diseases, leading to decreased mortality and increased life expectancy. However, recent years have seen an alarming rise in the number and frequency of antibiotic-resistant "Superbugs." The Centers for Disease Control and Prevention (CDC) estimates that over two million antibiotic-resistant infections occur in the United States annually, resulting in approximately 23,000 deaths. Despite the danger to public health, a minimal number of new antibiotic drugs are currently in development or in clinical trials by major pharmaceutical companies. To prevent reverting back to the pre-antibiotic era—when diseases caused by parasites or infections were virtually untreatable and frequently resulted in death—new and innovative approaches are needed to combat the increasing resistance of pathogenic bacteria to antibiotics. Bacterial Resistance to Antibiotics – From Molecules to Man examines the current state and future direction of research into developing clinically-useful next-generation novel antibiotics. An internationally-recognized team of experts cover topics including glycopeptide antibiotic resistance, anti-tuberculosis agents, anti-virulence therapies, tetracyclines, the molecular and structural determinants of resistance, and more. Presents a multidisciplinary approach for the optimization of novel antibiotics for maximum potency, minimal toxicity, and appropriated degradability Highlights critical aspects that may relieve the problematic medical situation of antibiotic resistance Includes an overview of the genetic and molecular mechanisms of antibiotic resistance Addresses contemporary issues of global public health and longevity Includes full references, author remarks, and color illustrations, graphs, and charts Bacterial Resistance to Antibiotics – From Molecules to Man is a valuable source of up-to-date information for medical practitioners, researchers, academics, and professionals in public health, pharmaceuticals, microbiology, and related fields.
