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https://www.readbyqxmd.com/read/28531310/nascent-rna-sequencing-reveals-mechanisms-of-gene-regulation-in-the-human-malaria-parasite-plasmodium-falciparum
#1
Xueqing Maggie Lu, Gayani Batugedara, Michael Lee, Jacques Prudhomme, Evelien M Bunnik, Karine G Le Roch
Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (IDC); however, the just-in-time transcriptional model has recently been challenged by findings that show the importance of post-transcriptional regulation. To further explore the role of transcriptional regulation, we performed the first genome-wide nascent RNA profiling in P...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531230/identifying-artemisinin-resistance-from-parasite-clearance-half-life-data-with-a-simple-shiny-web-application
#2
Sai Thein Than Tun, Yoel Lubell, Arjen M Dondorp, Tom Fieldman, Kyaw Myo Tun, Olivier Celhay, Xin Hui Chan, Sompob Saralamba, Lisa J White
The emergence of artemisinin-resistant Plasmodium falciparum malaria is a major threat to malaria elimination. New tools for supporting the surveillance of artemisinin resistance are critical for current and future malaria control and elimination strategies. We have developed an open-access, user-friendly, web-based tool to analyse parasite clearance half-life data of P. falciparum infected patients after treatment with artemisinin derivatives, so that resistance to artemisinin can be identified. The tool can be accessed at bit...
2017: PloS One
https://www.readbyqxmd.com/read/28531172/experimental-evaluation-of-cryopreservative-solutions-to-maintain-in-vitro-and-in-vivo-infectivity-of-p-berghei-sporozoites
#3
Naresh Singh, Samantha J Barnes, Sandra Kennedy, John H Adams
The rodent malaria parasite Plasmodium berghei is an excellent model organism for laboratory-based experimental evaluation of anti-malarial therapeutics prior to studies with human malaria parasites. The rodent model is especially important for evaluation of pre-erythrocytic (PE) stage therapies, especially as current efforts to develop new PE vaccines and drugs is limited by access to P. falciparum and P. vivax sporozoites. Developing a more effective method for cryopreservation of sporozoites would help improve access to sporozoites for laboratories lacking suitable insectary facilities...
2017: PloS One
https://www.readbyqxmd.com/read/28529974/a-glycosylphosphatidylinositol-anchored-carbonic-anhydrase-related-protein-of-toxoplasma-gondii-is-important-for-rhoptry-biogenesis-and-virulence
#4
Nathan M Chasen, Beejan Asady, Leandro Lemgruber, Rossiane C Vommaro, Jessica C Kissinger, Isabelle Coppens, Silvia N J Moreno
Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related to α-carbonic anhydrases (α-CAs). These CARPs are found in animals (both vertebrates and invertebrates) and viruses as either independent proteins or domains of other proteins. We report here the identification of a new CARP (TgCA_RP) in the unicellular organism Toxoplasma gondii that is related to the recently described η-class CA found in Plasmodium falciparum. TgCA_RP is posttranslationally modified at its C terminus with a glycosylphosphatidylinositol anchor that is important for its localization in intracellular tachyzoites...
May 2017: MSphere
https://www.readbyqxmd.com/read/28527688/clinical-development-of-a-var2csa-based-placental-malaria-vaccine-pamvac-quantifying-vaccine-antigen-specific-memory-b-t-cell-activity-in-beninese-primigravidae
#5
Komi Gbédandé, Nadine Fievet, Firmine Viwami, Sem Ezinmegnon, Saadou Issifou, Jean-Philippe Chippaux, Yannelle Dossou, Kabirou Moutairou, Achille Massougbodji, Nicaise Ndam, Willem Adriaan de Jongh, T Max M Søgaard, Ali Salanti, Morten A Nielsen, Meral Esen, Benjamin Mordmüller, Philippe Deloron, Adrian J F Luty
BACKGROUND: The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC's clinical development, we quantified naturally acquired vaccine antigen-specific memory B and T cell responses in Beninese primigravidae recruited at the beginning of pregnancy and followed up to delivery and beyond...
May 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28526680/decrease-in-numbers-of-naive-and-resting-b-cells-in-hiv-infected-kenyan-adults-leads-to-a-proportional-increase-in-total-and-plasmodium-falciparum-specific-atypical-memory-b-cells
#6
Anne E Frosch, Oludare A Odumade, Justin J Taylor, Kathleen Ireland, George Ayodo, Bartholomew Ondigo, David L Narum, John Vulule, Chandy C John
Human immunodeficiency virus type 1 (HIV-1) infection is associated with B cell activation and exhaustion, and hypergammaglobulinemia. How these changes influence B cell responses to coinfections such as malaria is poorly understood. To address this, we compared B cell phenotypes and Abs specific for the Plasmodium falciparum vaccine candidate apical membrane Ag-1 (AMA1) in HIV-infected and uninfected adults living in Kenya. Surprisingly, HIV-1 infection was not associated with a difference in serum AMA1-specific Ab levels...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526032/multiplex-dnase-free-one-step-reverse-transcription-pcr-for-plasmodium-18s-rrna-and-spliced-gametocyte-specific-mrnas
#7
Amelia E Hanron, Zachary P Billman, Annette M Seilie, Tayla M Olsen, Matthew Fishbaugher, Ming Chang, Thomas Rueckle, Nicole Andenmatten, Bryan Greenhouse, Emmanuel Arinaitwe, John Rek, Smita Das, Gonzalo J Domingo, Kelly Shipman, Stefan H Kappe, James G Kublin, Sean C Murphy
BACKGROUND: Plasmodium gametocytes are sexual stages transmitted to female Anopheles mosquitoes. While Plasmodium parasites can be differentiated microscopically on Giemsa-stained blood smears, molecular methods are increasingly used because of their increased sensitivity. Molecular detection of gametocytes requires methods that discriminate between asexual and sexual stage parasites. Commonly tested gametocyte-specific mRNAs are pfs25 and pfs230 detected by reverse transcription polymerase chain reaction (RT-PCR)...
May 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28526019/mass-anti-malarial-administration-in-western-cambodia-a-qualitative-study-of-factors-affecting-coverage
#8
Christopher Pell, Rupam Tripura, Chea Nguon, Phaikyeong Cheah, Chan Davoeung, Chhouen Heng, Lim Dara, Ma Sareth, Arjen Dondorp, Lorenz von Seidlein, Thomas J Peto
BACKGROUND: Mass anti-malarial administration has been proposed as a key component of the Plasmodium falciparum malaria elimination strategy in the Greater Mekong sub-Region. Its effectiveness depends on high levels of coverage in the target population. This article explores the factors that influenced mass anti-malarial administration coverage within a clinical trial in Battambang Province, western Cambodia. METHODS: Qualitative data were collected through semi-structured interviews and focus group discussions with villagers, in-depth interviews with study staff, trial drop-outs and refusers, and observations in the communities...
May 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28525963/the-use-of-transgenic-parasites-in-malaria-vaccine-research
#9
Ahmad Syibli Othman, Catherin Marin-Mogollon, Ahmed M Salman, Blandine M Franke-Fayard, Chris J Janse, Shahid M Khan
Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas Covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection...
May 19, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28524208/microfluidic-analysis-of-red-blood-cell-deformability-as-a-means-to-assess-hemin-induced-oxidative-stress-resulting-from-plasmodium-falciparum-intraerythrocytic-parasitism
#10
Kerryn Matthews, Simon P Duffy, Marie-Eve Myrand-Lapierre, Richard R Ang, Li Li, Mark D Scott, Hongshen Ma
Hemolytic anemia is one of the hallmarks of malaria and leads to an increase in oxidized heme (hemin) within the plasma of infected individuals. While scavenger proteins sequester much of the circulating heme, it has been hypothesized that extracellular heme may play a central role in malaria pathogenesis. We have previously developed the multiplex fluidic plunger (MFP) device for the measurement of red blood cell (RBC) deformability. Here, we demonstrate that the measurement of changes in RBC deformability is a sensitive method for inferring heme-induced oxidative stress...
May 19, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28523625/identification-of-a-novel-putative-inhibitor-of-the-plasmodium-falciparum-purine-nucleoside-phosphorylase-exploring-the-purine-salvage-pathway-to-design-new-antimalarial-drugs
#11
Luciano Porto Kagami, Gustavo Machado das Neves, Ricardo Pereira Rodrigues, Vinicius Barreto da Silva, Vera Lucia Eifler-Lima, Daniel Fábio Kawano
Malaria, a tropical parasitic disease caused by Plasmodium spp., continues to place a heavy social burden, with almost 200 million cases and more than 580,000 deaths per year. Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) can be targeted for antimalarial drug design since its inhibition kills malaria parasites both in vitro and in vivo. Although the currently known inhibitors of PfPNP, immucillins, are orally available and of low toxicity to animals and humans, to the best of our knowledge, none of these compounds has entered clinical trials for the treatment of malaria...
May 18, 2017: Molecular Diversity
https://www.readbyqxmd.com/read/28522856/diagnosing-congenital-malaria-in-a-high-transmission-setting-clinical-relevance-and-usefulness-of-p-falciparum-hrp2-based-testing
#12
Hamtandi Magloire Natama, Delwendé Florence Ouedraogo, Hermann Sorgho, Eduard Rovira-Vallbona, Elisa Serra-Casas, M Athanase Somé, Maminata Coulibaly-Traoré, Petra F Mens, Luc Kestens, Halidou Tinto, Anna Rosanas-Urgell
Congenital malaria diagnosis is challenging due to frequently observed low parasite density infections, while their clinical relevance during early infancy is not well characterized. In Nanoro health district (Burkina Faso), we determined the prevalence of congenital malaria by real-time quantitative PCR and we assessed the performance of rapid diagnosis test (RDT) and light microscopy (LM) to detect Plasmodium falciparum infections in cord-blood samples. In addition, we examined the usefulness of P. falciparum Histidine Rich Protein2 (PfHRP2) as surrogate biomarker of infection and explored association between congenital malaria and clinical outcomes...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522690/resistance-to-malaria-through-structural-variation-of-red-blood-cell-invasion-receptors
#13
Ellen M Leffler, Gavin Band, George B J Busby, Katja Kivinen, Quang Si Le, Geraldine M Clarke, Kalifa A Bojang, David J Conway, Muminatou Jallow, Fatoumatta Sisay-Joof, Edith C Bougouma, Valentina D Mangano, David Modiano, Sodiomon B Sirima, Eric Achidi, Tobias O Apinjoh, Kevin Marsh, Carolyne M Ndila, Norbert Peshu, Thomas N Williams, Chris Drakeley, Alphaxard Manjurano, Hugh Reyburn, Eleanor Riley, David Kachala, Malcolm Molyneux, Vysaul Nyirongo, Terrie Taylor, Nicole Thornton, Louise Tilley, Shane Grimsley, Eleanor Drury, Jim Stalker, Victoria Cornelius, Christina Hubbart, Anna E Jeffreys, Kate Rowlands, Kirk A Rockett, Chris C A Spencer, Dominic P Kwiatkowski
The malaria parasite Plasmodium falciparum invades human red blood cells via interactions between host and parasite surface proteins. By analyzing genome sequence data from human populations, including 1269 individuals from sub-Saharan Africa, we identify a diverse array of large copy number variants affecting the host invasion receptor genes GYPA and GYPB We find that a nearby association with severe malaria is explained by a complex structural rearrangement involving the loss of GYPB and gain of two GYPB-A hybrid genes, which encode a serologically distinct blood group antigen known as Dantu...
May 18, 2017: Science
https://www.readbyqxmd.com/read/28522546/the-rxlr-motif-of-the-host-targeting-effector-avr3a-of-phytophthora-infestans-is-cleaved-before-secretion
#14
Stephan Wawra, Franziska Trusch, Anja Matena, Kostis Apostolakis, Uwe Linne, Igor Zhukov, Jan Stanek, Wiktor Koźmiński, Ian Davidson, Chris J Secombes, Peter Bayer, Pieter van West
When plant-pathogenic oomycetes infect their hosts, they employ a large arsenal of effector proteins to establish a successful infection. Some effector proteins are secreted and are destined to be translocated and function inside host cells. The largest group of translocated proteins from oomycetes are the RxLR effectors, defined by their conserved N-terminal Arg-Xaa-Leu-Arg (RxLR) motif. However, the precise role of this motif in the host cell translocation process is unclear. Here detailed biochemical studies of the RxLR effector AVR3a from the potato pathogen Phytophthora infestans are presented...
May 18, 2017: Plant Cell
https://www.readbyqxmd.com/read/28521900/diagnosis-of-malarial-infection-using-change-in-properties-of-optically-trapped-red-blood-cells
#15
Apurba Paul, Ponnan Padmapriya, Vasant Natarajan
BACKGROUND: In previous work studying the properties of red blood cells (RBCs) held in an optical tweezers trap, we observed an increase in the spectrum of Brownian fluctuations for RBCs from a Plasmodium falciparum culture-due to increased rigidity of the cells-compared to normal RBCs. We wanted to extend the study to patient samples, since the earlier work was done with cultures grown in the lab. METHODS: Individual RBCs were held in an optical-tweezers trap. Its position fluctuations were measured and the power spectrum determined...
April 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28521798/use-of-malaria-rdts-in-various-health-contexts-across-sub-saharan-africa-a-systematic-review
#16
Matthew R Boyce, Wendy P O'Meara
BACKGROUND: The World Health Organization recommends parasitological confirmation of malaria prior to treatment. Malaria rapid diagnostic tests (RDTs) represent one diagnostic method that is used in a variety of contexts to overcome limitations of other diagnostic techniques. Malaria RDTs increase the availability and feasibility of accurate diagnosis and may result in improved quality of care. Though RDTs are used in a variety of contexts, no studies have compared how well or effectively RDTs are used across these contexts...
May 18, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28515136/loss-of-humoral-and-cellular-immunity-to-invasive-nontyphoidal-salmonella-during-current-or-convalescent-plasmodium-falciparum-infection-in-malawian-children
#17
Tonney S Nyirenda, James T Nyirenda, Dumizulu L Tembo, Janet Storm, Queen Dube, Chisomo L Msefula, Kondwani C Jambo, Henry C Mwandumba, Robert S Heyderman, Melita A Gordon, Wilson L Mandala
Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with Plasmodium falciparum infections, but the immunologic basis for this linkage is poorly understood. We hypothesized that P. falciparum infection compromises the hosts' humoral and cellular immunity to NTS which increases their susceptibility to iNTS infection. We prospectively recruited children aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi and allocated them to the following groups; febrile with uncomplicated malaria, febrile malaria-negative, non-febrile malaria-negative...
May 17, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28515133/development-of-a-novel-virus-like-particle-vaccine-platform-that-mimics-immature-form-of-alphavirus
#18
Akane Urakami, Atsuko Sakurai, Momoko Ishikawa, Moh Lan Yap, Yevel Flores-Garcia, Yasunari Haseda, Taiki Aoshi, Fidel P Zavala, Michael G Rossmann, Sachiko Kuno, Ryuji Ueno, Wataru Akahata
Virus-like particles (VLPs) are non-infectious multiprotein structures that are engineered to self-assemble from viral structural proteins. Here, we developed a novel VLP-based vaccine platform utilizing VLPs from the Chikungunya virus. We identified two regions within the envelope protein, a structural component of Chikungunya, where foreign antigens can be inserted without compromising VLP structure. Our VLP displays 480 copious copies of an inserted antigen on the VLP surface in a highly symmetric manner, thus capable of inducing strong immune responses against any inserted antigen...
May 17, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28513586/hundreds-of-dual-stage-antimalarial-molecules-discovered-by-a-functional-gametocyte-screen
#19
Celia Miguel-Blanco, Irene Molina, Ana I Bardera, Beatriz Díaz, Laura de Las Heras, Sonia Lozano, Carolina González, Janneth Rodrigues, Michael J Delves, Andrea Ruecker, Gonzalo Colmenarejo, Sara Viera, María S Martínez-Martínez, Esther Fernández, Jake Baum, Robert E Sinden, Esperanza Herreros
Plasmodium falciparum stage V gametocytes are responsible for parasite transmission, and drugs targeting this stage are needed to support malaria elimination. We here screen the Tres Cantos Antimalarial Set (TCAMS) using the previously developed P. falciparum female gametocyte activation assay (Pf FGAA), which assesses stage V female gametocyte viability and functionality using Pfs25 expression. We identify over 400 compounds with activities <2 μM, chemically classified into 57 clusters and 33 singletons...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28510633/obesity-and-diabetes-as-risk-factors-for-severe-plasmodium-falciparum-malaria-results-from-a-swedish-nationwide-study
#20
Katja Wyss, Andreas Wångdahl, Maria Vesterlund, Ulf Hammar, Saduddin Dashti, Pontus Naucler, Anna Färnert
Background: Noncommunicable diseases and obesity are increasing in prevalence globally, also in populations at risk of malaria. We sought to investigate if comorbidity, in terms of chronic diseases and obesity, is associated with severe Plasmodium falciparum malaria. Methods: We performed a retrospective observational study in adults (≥18 years) diagnosed with malaria in Sweden between January 1995 and May 2015. We identified cases through the surveillance database at the Public Health Agency of Sweden and reviewed clinical data from 18 hospitals...
May 16, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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