Download or read book Organisation and Function of the Inner Membrane Complex of the Malaria Parasite Plasmodium Falciparum written by Jeffrey Aaron Yeoman and published by . This book was released on 2011 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Malaria written by Institute of Medicine and published by National Academies Press. This book was released on 1991-02-01 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death. This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities. The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the: Nature, clinical manifestations, diagnosis, and epidemiology of malaria. Biology of the malaria parasite and its vector. Prospects for developing malaria vaccines and improved treatments. Economic, social, and behavioral factors in malaria control.
Download or read book Sequence Specific Recruitment of Proteins to the Inner Membrane Complex of the Malaria Parasite Plasmodium Falciparum Welch 1897 written by Johanna Wetzel and published by . This book was released on 2014 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Malaria Parasites written by Andrew P. Waters and published by Caister Academic Press Limited. This book was released on 2004 with total page 578 pages. Available in PDF, EPUB and Kindle. Book excerpt: The completion of the Plasmodium falciparum genome sequence in late 2002 heralded a new era in malaria research. The search began in earnest for new drugs and vaccines to combat malaria, a disease which afflicts up to 500 million people worldwide and is responsible for the deaths of more than one million people each year. The new genomic data is aiding a greater understanding of the living parasite and its interaction with the insect vector and human host. In this book internationally renowned experts provide up-to-date reviews of the most important aspects of post-genomic malaria research. Topics covered include: the P. falciparum genome and model parasites, bioinformatics and genome databases, microsatellite analysis, analysis of chromosome structure, cell cycle to RNA polymerase I and II mediated gene expression, role of the nuclear genome, the parasite surface and cell biology, and much more. The book is essential to all researchers working in this highly topical field and is recommended reading for scientists in other areas of biology and medicine.
Download or read book Structure Function and Antibody mediated Inhibition of Plasmodium CelTOS a Protein that Enables Cell Traversal by Malaria Parasites written by John Rashid Jimah and published by . This book was released on 2017 with total page 142 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is an immense global health problem which is primarily caused by Plasmodium falciparum and Plasmodium vivax parasites. These parasites have a complex life cycle, with stages in the human host and mosquito vector, and traverse diverse host and vector cells. Cell traversal involves biological processes such as parasite motility, breaching of cell membranes, and immune evasion which are mediated by various Plasmodium proteins that are only now beginning to be identified. Genetic studies have implicated Plasmodium CelTOS (cell-traversal protein for ookinetes and sporozoites) in mediating the traversal of sporozoites through the mammalian liver sinusoidal layer and ookinetes through the mosquito midgut epithelium. Additionally, CelTOS is a promising malaria vaccine candidate, as immunization of mice with CelTOS elicits a protective humoral and cell-mediated immune response. An immune response to CelTOS in humans is also correlated with protection from malaria. Even though CelTOS has critical roles in Plasmodium biology and is a vaccine target, the molecular function and mechanism of CelTOS had been unknown, primarily due to its lack of sequence similarity to proteins of known function.In our studies, we investigated the biophysical function of CelTOS to gain insight into its role during cell traversal. We determined the structure of PvCelTOS and observed similarity to proteins that bind and disrupt cell membranes, including HIV-1 gp41 and the Mycobacterium toxin ESAT-6. The structural similarity of CelTOS to these proteins informed the hypothesis that CelTOS binds and disrupts host and vector cell plasma membranes to enable the exit of parasites out of invaded cells during traversal. Subsequent investigations revealed that CelTOS specifically binds phosphatidic acid, a lipid predominantly present within the inner leaflet of cell plasma membranes, and disrupts liposomes composed of this lipid by pore-formation. Furthermore, microinjection of CelTOS into Xenopus oocytes damaged the plasma membrane and resulted in leakage of the cytosol. Taken together, we have identified CelTOS as the first Plasmodium protein that enables the exit of malaria parasites from host and vector cells.Given that CelTOS enables the progression of parasites through stages in the mosquito vector and human host, it is a unique malaria vaccine candidate that may block both malaria transmission and infection. Immunization with CelTOS elicits antibodies that have been shown to inhibit malaria infection in mice. CelTOS antibodies also block ookinete development into oocysts, an important step in sporozoite development within mosquitoes. We investigated the mechanism of antibody-mediated inhibition of CelTOS by identifying the epitopes in CelTOS targeted by neutralizing and non-neutralizing antibodies. The crystal structures of CelTOS in complex with neutralizing antibodies delineate residues that are targeted by antibodies that block CelTOS-mediated membrane disruption. Identification of neutralizing epitopes in CelTOS will inform the design of immunogens that elicit potent neutralizing antibodies.In summary, our findings reveal CelTOS targets the inner leaflet of host and vector cell plasma membranes by pore formation which may enable the exit of parasites during cell traversal. Additionally, we have identified epitopes in Plasmodium CelTOS that are targeted by antibodies, which begins to elucidate the mechanism of antibody-mediated inhibition of CelTOS. These findings provide a foundation for exploring the biophysical mechanism of CelTOS including the mechanisms of lipid binding, membrane insertion, and oligomerization within membranes to form pores. Also, the approaches used in this study may be applied to elucidate the role of putative pore-forming proteins, such as SPECT2 and MAOP, which mediate other steps in cell traversal. Finally, by determining the structure of CelTOS and developing an in vitro method for testing CelTOS activity, this study will inform the design and screening of therapeutics and vaccines which target CelTOS to protect against malaria.
Download or read book Molecular Characterization of Membrane Associated Inner Membrane Complex Proteins in Plasmodium Falciparum Welch 1897 written by Dipto Sinha and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Manson s Tropical Diseases E Book written by Jeremy Farrar and published by Elsevier Health Sciences. This book was released on 2013-10-26 with total page 1530 pages. Available in PDF, EPUB and Kindle. Book excerpt: From the difficult to diagnose to the difficult to treat, Manson’s Tropical Diseases prepares you to effectively handle whatever your patients may have contracted. Featuring an internationally recognized editorial team, global contributors, and expert authors, this revised and updated medical reference book provides you with the latest coverage on parasitic and infectious diseases from around the world. Consult this title on your favorite e-reader, conduct rapid searches, and adjust font sizes for optimal readability. Incorporate the latest therapies into your practice, such as recently approved drugs and new treatment options. Find what you need easily and apply it quickly with highlighted key information, convenient boxes and tables, extensive cross-referencing, and clinical management diagrams. Make the most accurate Tropical Disease diagnoses through a completely redesigned and modernized format, which includes full-color images throughout. Apply the latest treatment strategies for HIV/AIDS, tropical neurology, malaria, and much more. Put the latest international expertise to work for you and your patients with new chapters covering Global Health; Global Health Governance and Tropical Diseases; Non-communicable Diseases; Obesity in the Tropics; and Emergency and Intensive Care Medicine in Resource-poor Settings. See which diseases are most prevalent in specific areas of the tropics through a new index of diseases by country, as well as online-only maps that provide additional detail. Better understand the variations in treatment approaches across the globe.
Download or read book Ireland in Reality Or the True Interest of the Labourer written by and published by . This book was released on 1848 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Current Topics in Malaria written by Alfonso J. Rodriguez-Morales and published by . This book was released on 2016-11-30 with total page 508 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 CryoEM Enabled Approaches to Structure Determination of Endogenous Protein Complexes Implicated in the Pathogenesis of the Malaria Parasite Plasmodium Falciparum written by Chi-Min Ho and published by . This book was released on 2019 with total page 151 pages. Available in PDF, EPUB and Kindle. Book excerpt: The complexity and breadth of the host-cell remodeling machinery in the malaria parasite P. falciparum make it a rich and exciting system for the study of host-pathogen interfaces, particularly as many of the molecular mechanisms underlying this parasite's ability to hijack human red blood cells remain unclear. Furthermore, the P. falciparum proteome has proven recalcitrant to structural and biochemical characterization using recombinant methods, making it an intriguing model system for the development of new methods that leverage recent advances in cryoEM to enable structural studies of previously intractable systems at near-atomic resolution. The work presented here makes significant contributions in both these regards. First, we use a targeted, CRISPR-enabled "top down" approach to determine near-atomic resolution structures of the unique malaria parasite translocon PTEX, which we purified directly from P. falciparum parasites in multiple functional states, yielding the first near-atomic resolution cryoEM structures of a protein isolated directly from an endogenous source using an epitope tag inserted into the endogenous locus with CRISPR-Cas9 gene editing. We then developed a "bottom up" endogenous structural proteomics method whereby protein complexes enriched directly from the cellular milieu are identified by imaging and structure determination using cryoEM and mass spectrometry. As a proof of principle, we successfully used this approach to obtain near-atomic resolution structures of multiple protein complexes from the P. falciparum proteome, which has previously proven recalcitrant to expression in recombinant systems, precluding structure determination by X-ray crystallography or NMR. The body of work described here addresses a known need for methods that overcome the limitations of structural biology approaches that depend on recombinant systems, opening the door for high resolution structure determination of a vast number of previously intractable biological systems.
Download or read book Characterisation of the Plasmodium Falciparum Export Complex written by Brendan Elsworth and published by . This book was released on 2015 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium parasites extensively remodel the mammalian host cells they infect, namely the erythrocytes and hepatocytes. This is achieved through exporting hundreds of parasite proteins into the host where they play many virulence related roles including altering membrane permeability to acquire nutrients for rapid growth and for increasing immune evasion. Proteins are secreted from the parasite into the vacuole that surrounds them, where they must then pass across the parasitophorous vacuole membrane (PVM) to gain access to the host cytoplasm. It has previously been shown that a protein complex, the Plasmodium Translocon of EXported proteins (PTEX), is found on the PVM and is most likely the protein translocon responsible for this export process. To validate and further dissect PTEX function, a conditional expression system that utilizes the glmS riboswitch was employed to conditionally knockdown the levels of PTEX150 within parasites. Using this approach, even a relatively low level of PTEX150 knockdown lead to a significant decrease in the ability of the parasites to export proteins across the PVM. This failure of protein export across the PVM arrested growth and eventually caused parasite death. Interestingly, the export of all classes of protein cargoes tested, including PfEMP1, were blocked upon PTEX150 knockdown suggesting PTEX may serve as a single portal for export. This demonstrates the importance of PTEX to the malaria parasite and validates it as a potent drug target, since blocking it would prevent hundreds of exported proteins from reaching their functional destinations. To further investigate the specific function of PTEX150 we performed C-terminal truncations in order to generate a parasite line with a partially defective protein. These lines showed destabilisation of the PTEX complex, suggesting that the C-terminus of PTEX150, while not essential for PTEX function or the absolute binding of the other components, is required for stabilising the PTEX complex. Interestingly, these parasites did not show a defect in either their ability to grow or export proteins. To further investigate the effect of PTEX150 knockdown on parasite health the new permeability pathways (NPPs) were investigated. To do this a novel method was developed to investigate NPP function using luciferase. This method is highly sensitive, reducing the amount of parasites required as well as removing the need to purify parasites from culture. The effect of PTEX150 knockdown on NPPs was unclear using this method. Due to the high sensitivity and ease of this method it was developed as a HTS to discover NPP inhibitors. Using this method the malaria box of 400 compounds was screened. Importantly, two compounds, MMV020439and MMV007571, showed inhibitory activity significantly higher than the control compound NPPB.
Download or read book Apicomplexan Parasites written by Katja Becker and published by John Wiley & Sons. This book was released on 2011-01-19 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: This handbook is the first dealing with the discovery of drugs directed against apicomplexan parasites. Amongst others, this group of endoparasites includes the causative agents of Malaria, Toxoplasmosis, and Babesiosis, the latter occurring mainly in animals. Written by renowned scientific experts from academia and industry, the book focuses on currentdrug development approaches for all apicomplexan diseases making it appealing to a large audience, ranging from research labs in academia to the human and veterinarian pharmaceutical industry. This work is the second volume of the new book series 'Drug Discovery in Infectious Diseases', edited by Prof. Dr Paul M. Selzer.
Download or read book Malaria written by Dyann Fergus Wirth and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is a mosquito-borne disease caused by parasitic protozoa that belong to the genus Plasmodium. This disease imposes a significant global health burden, claiming the lives of several thousand children and pregnant women each day. Increasing antimalarial drug resistance and the complexity of the Plasmodium life cycle, among other factors, have made eradication difficult. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines the biology, pathology, and epidemiology of malaria, as well as ongoing efforts to treat infections and manage their spread. Contributors discuss the Plasmodium life cycle, focusing on the molecular mechanisms by which the various parasitic stages induce clinical symptoms, interact with the immune system, and lead to further transmission of malaria. They also explore topics such as the interaction between mosquito reproduction and Plasmodium development, epigenetic regulation of malaria-associated genes, and unique features of malaria in pregnant women (e.g., parity-dependent susceptibility) and describe how an improved understanding of these phenomena may lead to novel intervention strategies. The driving forces behind antimalarial drug resistance are covered, as is progress in developing an effective vaccine and controlling mosquito populations. This volume is therefore an essential reference for all scientists, clinicians, and public health professionals interested in understanding malaria and reducing its devastating effects.
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 World malaria report 2017 written by World Health Organization and published by World Health Organization. This book was released on 2018-02-12 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Malaria Report 2017 presents a comprehensive state of play in global progress in the fight against malaria up to the end of 2016. It tracks progress in investments in malaria programs and research, malaria prevention, diagnosis and treatment, surveillance, trends in malaria disease burden, malaria elimination, and threats in tackling malaria and safeguarding the investments made. The report draws on data from 91 countries and areas with ongoing malaria transmission. The information is supplemented by data from national household surveys and databases held by other organizations. This year's report shows that after an unprecedented period of success in global malaria control, progress has stalled. In 2016, there were an estimated 216 million cases of malaria, an increase of about 5 million cases over 2015. Deaths reached 445,000, a similar number to the previous year.
