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https://www.readbyqxmd.com/read/28211852/plasmodium-falciparum-crk4-directs-continuous-rounds-of-dna-replication-during-schizogony
#1
Markus Ganter, Jonathan M Goldberg, Jeffrey D Dvorin, Joao A Paulo, Jonas G King, Abhai K Tripathi, Aditya S Paul, Jing Yang, Isabelle Coppens, Rays H Y Jiang, Brendan Elsworth, David A Baker, Rhoel R Dinglasan, Steven P Gygi, Manoj T Duraisingh
Plasmodium parasites, the causative agents of malaria, have evolved a unique cell division cycle in the clinically relevant asexual blood stage of infection(1). DNA replication commences approximately halfway through the intracellular development following invasion and parasite growth. The schizont stage is associated with multiple rounds of DNA replication and nuclear division without cytokinesis, resulting in a multinucleated cell. Nuclei divide asynchronously through schizogony, with only the final round of DNA replication and segregation being synchronous and coordinated with daughter cell assembly(2,3)...
February 17, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28209188/erratum-to-characterization-of-a-plasmodium-berghei-sexual-stage-antigen-pbph-as-a-new-candidate-for-malaria-transmission-blocking-vaccine
#2
Xu Kou, Wenqi Zheng, Feng Du, Fei Liu, Meilian Wang, Qi Fan, Liwang Cui, Enjie Luo, Yaming Cao
No abstract text is available yet for this article.
February 16, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28159753/requirements-for-driving-anti-pathogen-effector-genes-into-populations-of-disease-vectors-by-homing
#3
Andrea Beaghton, Andrew Hammond, Tony Nolan, Andrea Crisanti, H Charles J Godfray, Austin Burt
There is a need for new interventions against the on-going burden of vector-borne diseases such as malaria and dengue. One suggestion has been to develop genes encoding effector molecules that block parasite development within the vector, and then use the nuclease-based homing reaction as a form of gene drive to spread those genes through target populations. If the effector gene reduces the fitness of the mosquito and does not contribute to the drive, then loss-of-function mutations in the effector will eventually replace functional copies, but protection may nonetheless persist sufficiently long to provide a public health benefit...
February 3, 2017: Genetics
https://www.readbyqxmd.com/read/28091576/adjuvant-and-carrier-protein-dependent-t-cell-priming-promotes-a-robust-antibody-response-against-the-plasmodium-falciparum-pfs25-vaccine-candidate
#4
Andrea J Radtke, Charles F Anderson, Nicolas Riteau, Kelly Rausch, Puthupparampil Scaria, Emily R Kelnhofer, Randall F Howard, Alan Sher, Ronald N Germain, Patrick Duffy
Humoral immune responses have the potential to maintain protective antibody levels for years due to the immunoglobulin-secreting activity of long-lived plasma cells (LLPCs). However, many subunit vaccines under development fail to generate robust LLPC responses, and therefore a variety of strategies are being employed to overcome this limitation, including conjugation to carrier proteins and/or formulation with potent adjuvants. Pfs25, an antigen expressed on malaria zygotes and ookinetes, is a leading transmission blocking vaccine (TBV) candidate for Plasmodium falciparum...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28087198/cloning-characterization-and-transmission-blocking-potential-of-midgut-carboxypeptidase-a-in-anopheles-stephensi
#5
V VenkatRao, Surendra K Kumar, P Sridevi, Vijaykumar Yogesh Muley, R K Chaitanya
Transmission-blocking vaccines (TBV) interrupt malaria parasite transmission and hence form an important component for malaria eradication. Mosquito midgut exopeptidases such as aminopeptidase N & carboxypeptidase B have demonstrated TBV potential. In the present study, we cloned and characterized carboxypeptidase A (CPA) from the midgut of an important malarial vector, Anopheles stephensi. ClustalW amino acid alignment and in silico 3-dimensional structure analysis of CPA predicted the presence of active sites involved in zinc and substrate binding that are conserved among all the known mosquito species...
January 10, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28057055/functional-characterization-of-plasmodium-berghei-psop25-during-ookinete-development-and-as-a-malaria-transmission-blocking-vaccine-candidate
#6
Wenqi Zheng, Fei Liu, Yiwen He, Qingyang Liu, Gregory B Humphreys, Takafumi Tsuboi, Qi Fan, Enjie Luo, Yaming Cao, Liwang Cui
BACKGROUND: Plasmodium ookinete surface proteins as post-fertilization target antigens are potential malaria transmission-blocking vaccine (TBV) candidates. Putative secreted ookinete protein 25 (PSOP25) is a highly conserved ookinete surface protein, and has been shown to be a promising novel TBV target. Here, we further investigated the TBV activities of the full-length recombinant PSOP25 (rPSOP25) protein in Plasmodium berghei, and characterized the potential functions of PSOP25 during the P...
January 5, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28043395/artesunate-tafenoquine-combination-therapy-promotes-clearance-and-abrogates-transmission-of-the-avian-malaria-parasite-plasmodium-gallinaceum
#7
Suchada Tasai, Tawee Saiwichai, Morakot Kaewthamasorn, Sonthaya Tiawsirisup, Prayute Buddhirakkul, Sirintip Chaichalotornkul, Sittiporn Pattaradilokrat
Clinical manifestations of malaria infection in vertebrate hosts arise from the multiplication of the asexual stage parasites in the blood, while the gametocytes are responsible for the transmission of the disease. Antimalarial drugs that target the blood stage parasites and transmissible gametocytes are rare, but are essentially needed for the effective control of malaria and for limiting the spread of resistance. Artemisinin and its derivatives are the current first-line antimalarials that are effective against the blood stage parasites and gametocytes, but resistance to artemisinin has now emerged and spread in various malaria endemic areas...
January 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28043178/towards-clinical-development-of-a-pfs48-45-based-transmission-blocking-malaria-vaccine
#8
Michael Theisen, Matthijs M Jore, Robert Sauerwein
Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45...
January 3, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28040374/the-rheopathobiology-of-plasmodium-vivax-and-other-important-primate-malaria-parasites
#9
REVIEW
Bruce M Russell, Brian M Cooke
Our current understanding of how malaria parasites remodel their host red blood cells (RBCs) and ultimately cause disease is largely based on studies of Plasmodium falciparum. In this review, we expand our knowledge to include what is currently known about pathophysiological changes to RBCs that are infected by non-falciparum malaria parasites. We highlight the potential folly of making generalizations about the rheology of malaria infection, and emphasize the need for more systematic studies into the erythrocytic biology of non-falciparum malaria parasites...
December 28, 2016: Trends in Parasitology
https://www.readbyqxmd.com/read/28027318/stage-specific-changes-in-plasmodium-metabolism-required-for-differentiation-and-adaptation-to-different-host-and-vector-environments
#10
Anubhav Srivastava, Nisha Philip, Katie R Hughes, Konstantina Georgiou, James I MacRae, Michael P Barrett, Darren J Creek, Malcolm J McConville, Andrew P Waters
Malaria parasites (Plasmodium spp.) encounter markedly different (nutritional) environments during their complex life cycles in the mosquito and human hosts. Adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (TCA) metabolism in mosquito stages. Here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage-specific changes in Plasmodium berghei carbon metabolism and determine the functional significance of these changes on parasite survival in the blood and mosquito stages...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27993160/erratum-to-an-optimised-age-based-dosing-regimen-for-single-low-dose-primaquine-for-blocking-malaria-transmission-in-cambodia
#11
Rithea Leang, Naw Htee Khu, Mavuto Mukaka, Mark Debackere, Rupam Tripura, Soy Ty Kheang, Say Chy, Neeraj Kak, Philippe Buchy, Arnaud Tarantola, Didier Menard, Arantxa Roca-Felterer, Rick M Fairhurst, Sim Kheng, Sinoun Muth, Song Ngak, Arjen M Dondorp, Nicholas J White, Walter Robert John Taylor
No abstract text is available yet for this article.
December 20, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27982038/release-of-plasmodium-sporozoites-requires-proteins-with-histone-fold-dimerization-domains
#12
Chiara Currà, Renate Gessmann, Tomasino Pace, Leonardo Picci, Giulia Peruzzi, Vassiliki Varamogianni-Mamatsi, Lefteris Spanos, Célia R S Garcia, Roberta Spaccapelo, Marta Ponzi, Inga Siden-Kiamos
The sporozoite, the stage of the malaria parasite transmitted by the mosquito, first develops for ∼2 weeks in an oocyst. Rupture of the oocyst capsule is required for release of sporozoites, which then transfer to the salivary gland where they are injected into a new host. Here we identify two parasite proteins that we call oocyst rupture proteins 1 (ORP1) and ORP2. These proteins have a histone-fold domain (HFD) that promotes heterodimer formation in the oocyst capsule at the time of rupture. Oocyst rupture is prevented in mutants lacking either protein...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27978709/a-malaria-transmission-blocking-usnic-acid-derivative-prevents-plasmodium-zygote-to-ookinete-maturation-in-the-mosquito-midgut
#13
Rebecca Pastrana-Mena, Derrick K Mathias, Michael Delves, Krithika Rajaram, Jonas G King, Rebecca Yee, Beatrice Trucchi, Luisella Verotta, Rhoel R Dinglasan
The evolution of drug resistance is a recurrent problem that has plagued efforts to treat and control malaria. Recent emergence of artemisinin resistance in Southeast Asia underscores the need to develop novel antimalarials and identify new targetable pathways in Plasmodium parasites. Transmission-blocking approaches, which typically target gametocytes in the host bloodstream or parasite stages in the mosquito gut, are recognized collectively as a strategy that when used in combination with antimalarials that target erythrocytic stages will not only cure malaria but will also prevent subsequent transmission...
December 16, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27977810/disrupting-mosquito-reproduction-and-parasite-development-for-malaria-control
#14
Lauren M Childs, Francisco Y Cai, Evdoxia G Kakani, Sara N Mitchell, Doug Paton, Paolo Gabrieli, Caroline O Buckee, Flaminia Catteruccia
The control of mosquito populations with insecticide treated bed nets and indoor residual sprays remains the cornerstone of malaria reduction and elimination programs. In light of widespread insecticide resistance in mosquitoes, however, alternative strategies for reducing transmission by the mosquito vector are urgently needed, including the identification of safe compounds that affect vectorial capacity via mechanisms that differ from fast-acting insecticides. Here, we show that compounds targeting steroid hormone signaling disrupt multiple biological processes that are key to the ability of mosquitoes to transmit malaria...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27938356/plasmodium-falciparum-genotype-and-gametocyte-prevalence-in-children-with-uncomplicated-malaria-in-coastal-ghana
#15
Ruth Ayanful-Torgby, Akua Oppong, Joana Abankwa, Festus Acquah, Kimberly C Williamson, Linda Eva Amoah
BACKGROUND: Plasmodium falciparum gametocytes are vital to sustaining malaria transmission. Parasite densities, multiplicity of infection as well as asexual genotype are features that have been found to influence gametocyte production. Measurements of the prevalence of Plasmodium sp. gametocytes may serve as a tool to monitor the success of malaria eradication efforts. METHODS: Whole blood was collected from 112 children aged between 6 months and 13 years with uncomplicated P...
December 9, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27930652/safety-and-reproducibility-of-a-clinical-trial-system-using-induced-blood-stage-plasmodium-vivax-infection-and-its-potential-as-a-model-to-evaluate-malaria-transmission
#16
Paul Griffin, Cielo Pasay, Suzanne Elliott, Silvana Sekuloski, Maggy Sikulu, Leon Hugo, David Khoury, Deborah Cromer, Miles Davenport, Jetsumon Sattabongkot, Karen Ivinson, Christian Ockenhouse, James McCarthy
BACKGROUND: Interventions to interrupt transmission of malaria from humans to mosquitoes represent an appealing approach to assist malaria elimination. A limitation has been the lack of systems to test the efficacy of such interventions before proceeding to efficacy trials in the field. We have previously demonstrated the feasibility of induced blood stage malaria (IBSM) infection with Plasmodium vivax. In this study, we report further validation of the IBSM model, and its evaluation for assessment of transmission of P...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27912985/immunogenicity-and-malaria-transmission-reducing-potency-of-pfs48-45-and-pfs25-encoded-by-dna-vaccines-administered-by-intramuscular-electroporation
#17
Dibyadyuti Datta, Geetha P Bansal, Dietlind L Gerloff, Barry Ellefsen, Drew Hannaman, Nirbhay Kumar
Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV). Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting. However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms. In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses...
January 5, 2017: Vaccine
https://www.readbyqxmd.com/read/27912876/in-vitro-and-ex-vivo-activity-of-an-azadirachta-indica-a-juss-seed-kernel-extract-on-early-sporogonic-development-of-plasmodium-in-comparison-with-azadirachtin-a-its-most-abundant-constituent
#18
Nisha Dahiya, Giuseppina Chianese, Solomon Mequanente Abay, Orazio Taglialatela-Scafati, Fulvio Esposito, Giulio Lupidi, Massimo Bramucci, Luana Quassinti, George Christophides, Annette Habluetzel, Leonardo Lucantoni
BACKGROUND: NeemAzal(®) (NA) is a quantified extract from seed kernels of neem, Azadirachta indica A.Juss. (Meliaceae), with a wide spectrum of biological properties, classically ascribed to its limonoid content. NA contains several azadirachtins (A to L), azadirachtin A (AzaA) being its main constituent. AzaA has been shown to inhibit microgamete formation of the rodent malaria parasite Plasmodium berghei, and NA was found to completely inhibit the transmission of Plasmodium berghei to Anopheles stephensi mosquitoes when administered to gametocytemic mice at a corresponding AzaA dose of 50mg/kg before exposure to mosquitoes...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27903741/whole-killed-blood-stage-vaccine-induced-immunity-suppresses-the-development-of-malaria-parasites-in-mosquitoes
#19
Feng Zhu, Taiping Liu, Chenhao Zhao, Xiao Lu, Jian Zhang, Wenyue Xu
As a malaria transmission-blocking vaccine alone does not confer a direct benefit to the recipient, it is necessary to develop a vaccine that not only blocks malaria transmission but also protects vaccinated individuals. In this study we observed that a whole-killed blood-stage vaccine (WKV) not only conferred protection against the blood-stage challenge but also markedly inhibited the transmission of different strains of the malaria parasite. Although the parasitemia is much lower in WKV-immunized mice challenged with malaria parasites, the gametocytemia is comparable between control and immunized mice during the early stages of infection...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27895131/the-plasmodium-falciparum-cell-traversal-protein-for-ookinetes-and-sporozoites-as-a-candidate-for-preerythrocytic-and-transmission-blocking-vaccines
#20
Diego A Espinosa, Joel Vega-Rodriguez, Yevel Flores-Garcia, Amy R Noe, Christian Muñoz, Russell Coleman, Torben Bruck, Keith Haney, Alex Stevens, Diane Retallack, Jeff Allen, Thomas S Vedvick, Christopher B Fox, Steven G Reed, Randall F Howard, Ahmed M Salman, Chris J Janse, Shahid M Khan, Fidel Zavala, Gabriel M Gutierrez
Recent studies have shown that immune responses against the cell-traversal protein for Plasmodium ookinetes and sporozoites (CelTOS) can inhibit parasite infection. While these studies provide important evidence toward the development of vaccines targeting this protein, it remains unknown whether these responses could engage the Plasmodium falciparum CelTOS in vivo Using a newly developed rodent malaria chimeric parasite expressing the P. falciparum CelTOS (PfCelTOS), we evaluated the protective effect of in vivo immune responses elicited by vaccination and assessed the neutralizing capacity of monoclonal antibodies specific against PfCelTOS...
February 2017: Infection and Immunity
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