Download or read book Dissecting Mechanisms of Antimalarials Using CRISPR Cas9 Editing in Plasmodium Falciparum written by SooNee Tan and published by . This book was released on 2019 with total page 123 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria, caused by Plasmodium infections, continues to be a global disease of public health importance with 300 million annual cases and about 500,000 deaths. Continual emergence of resistance to commonly used antimalarials underscores the importance of finding new drug targets and new antimalarial drugs. Previously, the Rathod lab has established systematic approaches to study targets of antimalarials and resistance mechanisms with the use of in vitro selection methods and deep sequencing of selected mutants. There are some limitations with these approaches as deep sequencing data does not reveal the stepwise mechanism of mutagenesis and mutations observed from the sequencing result might not associate with the resistance phenotype. This thesis has multiple projects aimed to expand the molecular toolbox with genome manipulation using CRISPR/Cas9 technique. It will complement the current tools that we have in performing target identification/validation as well as understanding the mechanism of mutagenesis in malaria parasites. Ciprofloxacin is an antibacterial known to target bacterial DNA Gyrase. In some instances, ciprofloxacin has been used for malaria prophylaxis but little is known about the mode-of-action of ciprofloxacin in malaria parasites. In the first project, we aim to understand the essentiality of Plasmodium falciparum DNA gyrase A subunit (PfGyrA) and its relationship with ciprofloxacin. Based on bioinformatics analyses, PfGyr A and B subunits are known to contain apicoplast-targeting signals. To test the predicted localization of this enzyme in the apicoplast and the function of this enzyme at the subcellular level, a CRISPR/Cas9 gene-editing tool was used to disrupt PfGyrA. It is known that isopentenyl pyrophosphate (IPP) rescues malaria parasites from apicoplast-targeting inhibitors and indeed successful growth of Pf[delta]GyrA required chemical rescue with IPP. PfGyrA disruption was accompanied by loss of the plastid acyl-carrier protein (ACP) immunouorescnce and the plastid genome. Drug sensitivity assays revealed that a Pf[delta]GyrA clone, supplemented with IPP was less sensitive to antibacterial compounds (doxycycline and ciprofloxacin) but not the nuclear topoisomerase inhibitor (etoposide). In addition, at high concentrations, ciprofloxacin continued to inhibit IPP-rescued Pf[delta]GyrA suggesting that this drug has an additional target in P. falciparum. We concluded that PfGyrA is an apicoplast enzyme in malaria parasite and it is essential for blood-stage parasites. In the future, untangling the two possible inhibitory functions of ciprofloxacin in malaria parasites may reveal a new and important drug target. The second project aim involves target validation of a tetrahydroquinolone compound, BMS-388891. Previous publications from the lab showed that resistance to BMS-388891 arises from a single point mutation in either the protein farnesyl transferase (PFT) alpha or beta subunit. Although results indicated that a single point mutation on the PfPFT enzyme led to BMS-3888891 resistant parasites, whole genome sequencing on those mutants have yet to be done. To test that a single mutation is sufficient for parasite acquisition of resistance to BMS-388891, gene alteration with CRISPR/Cas9 tool was utilized to introduce a point mutation (Y837N, Y837S, or Y837C) on the PFT-[Beta]-subunit. The CRISPR-modified mutant parasites have shown an increase of 10-20 fold resistance to BMS-388891. This data is the first to formally demonstrate that a single point mutation on the Pfpft-[Beta]-subunit is sufficient for parasites to confer resistance to BMS-388891 compound. There are very few validated compound to target relationships and CRISPR/Cas9 technique will be a valuable tool in the malaria field. The third project aim involves the understanding of the mechanism of mutagenesis in malaria parasites. While it is known that amplification and point mutation are the possible outcomes of resistance selection, the order of the processes is less understood. Recent work by Guler et. al. points to a novel step-wise amplification mechanism in the malarial parasite response to DSM1 selection pressure. In these selected parasites, 25-30 kb regions surrounding the Pfdhodh locus were amplified. Taking advantage of the highly amplified Pfdhodh locus, we were able to introduce Pfpft-[alpha]-subunit into this region. This sets up future studies for us to dissect the step-wise resistance mechanism in malaria parasites. Overall, the utilization of CRISPR/Cas9 tool has allowed us to efficiently perform gene knockout, gene alteration and gene translocation. These applications not only enable us to prove for the first time the importance of the PfGyrA enzyme but also to directly confirm the causality of specific point mutations in BMS-388891 resistant parasites. The addition of CRISPR/Cas9 gene-editing to our systematic approach toolbox will ultimately aid in our understanding of how mutagenesis occurs in malaria parasites and allow us to expand our knowledge in the mode-of-action of different antimalarials in P. falciparum.

Download or read book Membrane Transporters and Channels as Targets for Drugs written by Graça Soveral and published by Frontiers Media SA. This book was released on 2020-01-03 with total page 333 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transporters and channels are membrane proteins that mediate the traffic of metabolites, water and ions across biological membranes. Membrane transport proteins are crucial to maintain homeostasis and assure cell survival upon intracellular or environmental stress. A failure of any of these transport systems may have dramatic consequences for cell function. There is increasing evidence that membrane transport proteins play important functions in healthy conditions and that their absence or dysfunction may cause diseases. In recent years much attention has been paid to diseases resulting from defective transporters (“carrier diseases”) and ion channels (“channelopathies”). Very interestingly, altered expression of transporters has been described in several human pathologies. On this basis, many transport proteins are well acknowledged targets for drugs. Many others are involved in drug delivery and disposition and/or are considered potential targets. Others are off-targets for drugs and then, are responsible for side effects. Thus, membrane protein drug discovery is now an emerging field where the search for physiological mechanisms of regulation and for chemical compounds as modulators of transport activity, present new opportunities for drug development and for new therapies. This Research Topic addresses the latest research advances in membrane transport proteins, stimulating future research on these important protein families.

Download or read book Towards Malaria Elimination written by Sylvie Manguin and published by BoD – Books on Demand. This book was released on 2018-07-18 with total page 454 pages. Available in PDF, EPUB and Kindle. Book excerpt: Towards Malaria Elimination - A Leap Forward was started to mark the occasion for renewed commitment to end malaria transmission for good (the WHO's call for "Malaria Free World" by 2030). This book is dedicated for the benefit of researchers, scientists, program and policy managers, students and anyone interested in malaria and other mosquito-borne diseases with the goal of sharing recent information on success stories, innovative control approaches and challenges in different regions of the world. Some main issues that emerged included multidrug-resistant malaria and pandemic risk, vaccines, cross-border malaria, asymptomatic parasite reservoir, the threat of Plasmodium vivax and Plasmodium knowlesi, insecticide resistance in Anopheles vectors and outdoor malaria transmission. This book is one little step forward to bring together in 17 chapters the experiences of malaria-expert researchers from five continents to present updated information on disease epidemiology and control at the national/regional level, highlighting the constraints, challenges, accomplishments and prospects of malaria elimination.

Download or read book World Malaria Report 2019 written by World Health Organization and published by . This book was released on 2019-08-28 with total page 224 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Malaria Report 2019 provides a comprehensive update on global and regional malaria data and trends. The report tracks investments in malaria programs and research as well as progress across all intervention areas: prevention, diagnosis, treatment, elimination, and surveillance. It also includes dedicated chapters on the consequences of malaria on maternal infant and child health the "High Burden to High Impact" approach as well as biological threats to the fight against malaria. The 2019 report is based on information received from more than 80 countries and areas with ongoing malaria transmission. This information is supplemented by data from national household surveys and databases held by other organizations.

Download or read book Rodent Malaria written by R. Killick-Kendrick and published by Elsevier. This book was released on 2012-12-02 with total page 435 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rodent Malaria reviews significant findings concerning malaria parasites of rodents, including their taxonomy, zoogeography, and evolution, along with life cycles and morphology; genetics and biochemistry; and concomitant infections. This volume is organized into eight chapters and begins by sketching out the history of the discovery of rodent as well as aspects of parasitology, immunology, and chemotherapy. These concepts are investigated two decades following Ignace Vincke's major discovery and Meir Yoeli's successful establishment of the method of cyclical transmission of the parasite. The following chapters focus on the taxonomy and systematics of the subgenus Vinckeia, with reference to the concepts of species and subspecies of animals and the degree to which they apply to malaria parasites, in particular to those of rodents. The discussion then shifts to how the rodent malaria parasites provide a unique insight into the subcellular organization of Plasmodium species, the use of rodent malaria as an experimental model to study immunological responses, and infectious agents that interact with malaria parasites. The book concludes with a chapter on malaria chemotherapy, with emphasis on the value of rodent malaria in antimalarial drug screening and the use of antimalarial drugs as biological probes. This book will be of interest to protozoologists and physicians as well as those from other disciplines including biochemistry, immunology, pharmacology, cell biology, and genetics.

Download or read book Malaria written by Maria M. Mota and published by Springer. This book was released on 2017-01-12 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt: Currently, malaria kills more than 300,000 people per year, making it a top priority of world leaders and international organizations, who are working towards implementing and coordinating efforts to eradicate this disease. An effective malaria vaccine is recognized as the key element that will decide between success and failure in this fight. At present, despite intensive research efforts, such a vaccine is not yet available for use. However, there are a number of advanced candidate vaccines with high chances of success in the short term. Malaria: Immune Response to Infection and Vaccination provides a comprehensive view on the immune response to malaria and to the different vaccines under development. The book offers the following: - Contributions by top research leaders in the field, - Comparisons of the immune responses to both malaria infection and malaria vaccines, which are traditionally treated separately, - Coverage of the immune responses to the different stages of malaria, which are frequently treated as separate fields of research.

Download or read book Chemotherapy and Drug Resistance in Malaria written by Wallace Peters and published by . This book was released on 1987 with total page 822 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Medicinal Plants written by Halina Maria Ekiert and published by Springer Nature. This book was released on 2021-09-01 with total page 900 pages. Available in PDF, EPUB and Kindle. Book excerpt: Medicinal plant research is an evergreen subject. There is a tremendous increase in popularity of herbal medicine in traditional medicine, ethnomedicine, modern medicine and as over the counter food supplements. Even after this increased demand, supply is neither uniform nor assured as most of these plants are collected from wild. In developing countries of tropical and subtropical regions where majority of herbal drugs are produced, this is not organised sector making it vulnerable to several malpractices, hence standardization of all aspects required. This has also negative impact on biodiversity and conservation of plants as well as supply of uniform material. This book is aimed to provide up to date information about sustainable use of selected medicinal plants, their active ingredients and efforts made to domesticate them to ensured uniform supply. Development of agrotechnology, biotechnology and cultivation practices using conventional and non-conventional methods are presented. Where these efforts will lead the medicinal plant research and future perspective are discussed. The chapters are written by well recognised group leaders in working in the field. The book contains topics on general biology of medicinal plants, their sustainable use and, cultivation and domestication efforts. A uniform chapter structure has been designed to keep consistency. The book will be useful for academicians, agriculturists, biotechnologists and researcher, and industries involved in manufacturing herbal drugs and supplementary products.

Download or read book In vitro Plant Breeding towards Novel Agronomic Traits written by Manoj Kumar and published by Springer Nature. This book was released on 2019-11-23 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents a comprehensive overview of plant stresses caused by salt, drought, extreme temperatures, oxygen and toxic compounds, which are responsible for huge losses in crop yields. It discusses the latest research on the impact of salinity and global environment changes, and examines the advances in the identification and characterization of the mechanisms that allow plants to tolerate biotic and abiotic stresses. Further it presents our current understanding of metabolic fluxes and the various transporters that collectively open the possibility of applying in vitro technology and genetic engineering to improve stress tolerance. Exploring advanced methods that augment traditional plant tissue culture and breeding techniques toward the development of new crop varieties that can tolerate biotic and abiotic stresses to achieve sustainable food production, this book is a valuable resource for plant scientists and researchers.

Download or read book Toxicoepigenetics written by Shaun D. McCullough and published by Academic Press. This book was released on 2018-11-02 with total page 430 pages. Available in PDF, EPUB and Kindle. Book excerpt: Toxicoepigenetics: Core Principles and Applications examines the core aspects of epigenetics, including chromatin biology, DNA methylation, and non-coding RNA, as well as fundamental techniques and considerations for studying each of these mechanisms of epigenetic regulation. Although its integration into the field of toxicology is in its infancy, epigenetics have taken center stage in the study of diseases such as cancer, diabetes, and neurodegeneration. Increasing the presence of epigenetics in toxicological research allows for a more in-depth understanding of important aspects of toxicology such as the role of the environment and lifestyle influencing the individual susceptibility to these effects and the trans-generational transmission of these health effects and susceptibilities. Methods chapters are included to help improve efficacy and efficiency of protocols in both the laboratory and the classroom. Toxicoepigenetics: Core Principles and Applications is an essential book for researchers and academics using epigenetics in toxicology research and study. Introduces the fundamental principles and practices for understanding the role of the epigenome in toxicology Presents the foundation of epigenetics for toxicologists with a broad range of backgrounds Discusses the incorporation of epigenetics and epigenomics into current toxicological studies and interpretation of epigenetic data in toxicological applications

Download or read book Natural Antimicrobial Agents written by Jean-Michel Mérillon and published by Springer. This book was released on 2018-02-08 with total page 342 pages. Available in PDF, EPUB and Kindle. Book excerpt: Documenting the latest research in the field of different pathogenic organisms, this book presents the current scenario about promising antimicrobials in the following areas: Part I. Plants as source of antibacterials, Part II. Naturally occurring antifungal natural products, Part III. Antiparasitic natural products, Part IV. Antiviral natural products. Renowned scientists from the globe have been selected as authors to contribute chapters. Use of plants for various ailments is as old as human civilization and continuous efforts are being made to improve medicinal plants or to product their bioactive secondary metabolites in high amounts through various technologies. About 200,000 natural products of plant origin are known and many more are being identified from higher plants and micro-organisms. Some plants based drugs are used since centuries and there is no alternative medicine for many such drugs as cardiac glycosides. Drug discovery from medicinal plants or marine micro-organisms continues to provide an important source of new drug leads. Research on new antibacterials represents a real and timely challenge of this century, particularly for the treatment of infections caused by clinical isolates that show multidrug resistance. The main microorganisms involved in the resistance process have been identified and given the acronym ESKAPE for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa and Enterobacteriaceae. Multidrug resistant Mycobacterium tuberculosis including highly drug-resistant strains (XDR-TB) has also emerged as one of the most important clinical challenges of this century. Plants of diverse taxa and marine micro-organisms are rich source of these antimicrobials. An attempt has been made to compile the recent information about natural sources of antibacterials and their sustainable utilization. Increased panic of these pathogens warrants a growing demand for research to undertake the threat of multidrug resistance. The search for new antifungal, antiparasitic and antiviral natural products is far from devoid of interest. According to the WHO report in 2013, malaria still represents some 207 million cases worldwide and more than 3 billion of people are still exposed to this risk. Similarly, about 350 million people are considered at risk of contracting leishmaniasis. The fight against some viruses also requires that the research on natural products continue. For example, even if an antiretroviral with direct action was recently approved in Europe in 2013, its high cost does not allow to offer it to an exposed population in countries where the cost of drugs remains a problem for a large part of the population. These books are useful to researchers and students in microbiology, biotechnology, pharmacology, chemistry and biology as well as medical professionals.

Download or read book NanoBioEngineering written by Bhupinder Singh and published by CRC Press. This book was released on 2018-11-02 with total page 420 pages. Available in PDF, EPUB and Kindle. Book excerpt: The objective of this book is to provide the fundamental comprehension of a broad range of topics in an integrated volume such that readership hailing from diverse disciplines can rapidly acquire the necessary background for applying it in pertinent research and development field.

Download or read book Platform Technologies in Drug Discovery and Validation written by and published by Academic Press. This book was released on 2017-11-21 with total page 692 pages. Available in PDF, EPUB and Kindle. Book excerpt: Platform Technologies in Drug Discovery and Validation, Volume 50, the latest release in the Annual Reports in Medicinal Chemistry series, provides timely and critical reviews of important topics in medicinal chemistry, with an emphasis on emerging topics in the biological sciences. Topics covered in this new volume include DELT, Oligos: ASO, siRNA, CRISPR, Micro-fluidic chemistry, High throughput screening, Kinase-centric computational drug development, Virtual Screening, Phenotypic screening, PROTACS, Chemical Biology, Fragment-based lead generation, Antibody-Drug Conjugates, Antibody-recruiting small molecules, Deuteration, and Peptides. Unique for its treatment of platform technologies for medicinal chemistry and target validation Provides a single, rich volume that summaries a broad spectrum of expertise relevant to the field Presents state-of-the-art summaries of platform technologies

Download or read book Drug Discovery for Leishmaniasis written by Luis Rivas and published by Royal Society of Chemistry. This book was released on 2017-10-26 with total page 422 pages. Available in PDF, EPUB and Kindle. Book excerpt: For human health, leishmaniasis is among the most important protozoan diseases, superseded only by malaria. Globally, 10 to 12 million people are infected with 1.5 million new cases every year. The development of cheaper new drugs is urgently needed for this neglected disease that is developing resistance to current treatments. Chemotherapy remains the only treatment option for the bulk of patients. However, this is largely unaffordable for most. In the past three years numerous advances in drug discovery have been made for treating this disease by exploiting diverging metabolic pathways between the Leishmania enzymes and their hosts, using nanotechnology to target the immune cell phagolysosomes where Leishmania resides. Drug Discovery for Leishmaniasis aims to provide a perspective of the current treatments and their challenges, blended with the emerging strategies and methodologies that will drive new target appraisals and drug developments, as well as addressing the molecular basis of resistance in Leishmania. Recent studies have shown that leishmaniasis affects some of the poorest people in the world, with 95% of fatal cases occurring in only 6 countries. With the WHO goal of eliminating this public health problem in the South-east Asia Region by 2020, this book will be important for anyone who is interested in neglected tropical diseases.

Download or read book Pet to Man Travelling Staphylococci written by Vincenzo Savini and published by Academic Press. This book was released on 2018-03-14 with total page 324 pages. Available in PDF, EPUB and Kindle. Book excerpt: Pet-to-Man Travelling Staphylococci: A World in Progress explores Staphylococci, a dangerous pathogen that affects both humans and animals with a wide range of infection states. This bacteria can spread rapidly as a commensal organism in both humans and pets, and is an agent of disease. Staphylococci are potentially highly virulent pathogens which require urgent medical attention. In addition, Staphylococci remain a threat within hospital environments, where they can quickly spread across a patient population. This book explores the organisms' resistance to many compounds used to treat them, treatment failure and multidrug resistant staphylococci, amongst other related topics. Focuses not only on man and animal staphylococcal diseases, but on the role of shared household in man-to-pet (and vice versa) transmission Underlines the importance of professional exposure to mammals (i.e. veterinary and farm personnel) in the establishment of shared colonization's and related diseases Highlights the impact of shared staphylococci and virulence determinants in human and veterinary pathology Sheds light on the way staphylococci may be recognized in clinical laboratories

Download or read book Genetic Control of Malaria and Dengue written by Zach N. Adelman and published by Academic Press. This book was released on 2015-10-15 with total page 487 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic Control of Malaria and Dengue focuses on the knowledge, technology, regulation and ethics of using genetically modified mosquitoes to interrupt the transmission of important vector-borne diseases including Malaria. It contains coverage of the current state of knowledge of vector-borne diseases and how they are currently controlled; vaccine, drug and insecticide development; various strategies for altering the genome of mosquitoes in beneficial ways; and the regulatory, ethical and social environment concerning these strategies. For more than five decades, the prospect of using genetically-modified mosquitoes to control vector-borne disease transmission has been a purely hypothetical scenario. We simply did not have the technology or basic knowledge to be able to do it. With the explosion of field trials and potential interventions in development, Genetic Control of Malaria and Dengue provides a comprehensive overview of research in genetics, microbiology, virology, and ecology involved in the development and implementation of genetic modification programs for virus and disease control. This book is meant to provide a practical guide to researchers, regulators and the general public about how this technology actually works, how it can be improved, and what is still unknown. Includes coverage of vectorial capacity, critical to understanding vector-borne disease transmission Provides a summary of the concepts of both population suppression and population replacement Contains pivotal coverage of ethical and ecological ramifications of genetics-based control strategies

Download or read book Cell Penetrating Peptides written by Ülo Langel and published by Humana. This book was released on 2015-07-24 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Divided into three parts this volume summarizes the most important areas of Cell-Penetrating Peptides (CPP) research . Part one briefly presents the historical background of CPP studies and the classifications of the available CPPs, and then summarizes the approaches for prediction of novel CPPs. Part two mainly describes the methods for studies of “naked” CPPs, that is, CPPs without conjugated cargos. Last but not least part three presents a representative and brief summary of functionality issues of CPPs, both in vitro and in vivo. As a volume in the highly successful Methods in Molecular Biology series, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Concise and easy-to-use, Cell-Penetrating Peptides: Methods and Protocols, Second Edition hopes to raise relevant questions for further development.