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https://www.readbyqxmd.com/read/28635544/heparin-new-life-for-an-old-drug
#1
Carlos Raúl Aláez-Versón, Elena Lantero, Xavier Fernàndez-Busquets
Heparin is one of the oldest drugs, which nevertheless remains in widespread clinical use as an inhibitor of blood coagulation. The history of its identification a century ago unfolded amid one of the most fascinating scientific controversies turning around the distribution of credit for its discovery. The composition, purification and structure-function relationship of this naturally occurring glycosaminoglycan regarding its classical role as anticoagulant will be dealt with before proceeding to discuss its therapeutic potential in, among other, inflammatory and infectious disease, cancer treatment, cystic fibrosis and Alzheimer's disease...
June 21, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28634105/genetic-diversity-in-the-c-terminus-of-merozoite-surface-protein-1-among-plasmodium-knowlesi-isolates-from-selangor-and-sabah-borneo-malaysia
#2
Nan Jiun Yap, Xiang Ting Goh, Anson V Koehler, Timothy William, Tsin Wen Yeo, Indra Vythilingam, Robin B Gasser, Yvonne A L Lim
Plasmodium knowlesi, a malaria parasite of macaques, has emerged as an important parasite of humans. Despite the significance of P. knowlesi malaria in parts of Southeast Asia, very little is known about the genetic variation in this parasite. Our aim here was to explore sequence variation in a molecule called the 42kDa merozoite surface protein-1 (MSP-1), which is found on the surface of blood stages of Plasmodium spp. and plays a key role in erythrocyte invasion. Several studies of P. falciparum have reported that the C-terminus (a 42kDa fragment) of merozoite surface protein-1 (MSP-142; consisting of MSP-119 and MSP-133) is a potential candidate for a malaria vaccine...
June 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28630943/parasites-lacking-the-micronemal-protein-mic2-are-deficient-in-surface-attachment-and-host-cell-egress-but-remain-virulent-in-vivo
#3
Simon Gras, Allison Jackson, Stuart Woods, Gurman Pall, Jamie Whitelaw, Jacqueline M Leung, Gary E Ward, Craig W Roberts, Markus Meissner
Background: Micronemal proteins of the thrombospondin-related anonymous protein (TRAP) family are believed to play essential roles during gliding motility and host cell invasion by apicomplexan parasites, and currently represent major vaccine candidates against Plasmodium falciparum, the causative agent of malaria. However, recent evidence suggests that they play multiple and different roles than previously assumed. Here, we analyse a null mutant for MIC2, the TRAP homolog in Toxoplasma gondii. Methods: We performed a careful analysis of parasite motility in a 3D-environment, attachment under shear stress conditions, host cell invasion and in vivo virulence...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28630585/identification-of-the-plasmodium-species-in-clinical-samples-from-children-residing-in-five-epidemiological-strata-of-malaria-in-cameroon
#4
Tebit Emmanuel Kwenti, Tayong Dizzle Bita Kwenti, Longdoh Anna Njunda, Andreas Latz, Kukwah Anthony Tufon, Theresa Nkuo-Akenji
BACKGROUND: Malaria in Cameroon was previously known to be caused solely by Plasmodium falciparum but today, evidence points to other Plasmodium species including P. vivax, P. ovale and P. malariae. The purpose of this study was to identify the Plasmodium species in clinical samples from children residing in five epidemiological strata of malaria in Cameroon, so as to advise control policies. METHODS: One thousand six hundred nine febrile children (≤15 years) were recruited from five epidemiological strata of malaria including the Sudano-sahelian (SS) strata, the High inland plateau (HIP) strata, the South Cameroonian Equatorial forest (SCEF) strata, the High western plateau (HWP) strata and the Coastal (C) strata...
2017: Tropical Medicine and Health
https://www.readbyqxmd.com/read/28626547/structure-guided-optimization-of-quinoline-inhibitors-of-plasmodium-n-myristoyltransferase
#5
Victor Goncalves, James A Brannigan, Alice Laporte, Andrew S Bell, Shirley M Roberts, Anthony J Wilkinson, Robin J Leatherbarrow, Edward W Tate
The parasite Plasmodium vivax is the most widely distributed cause of recurring malaria. N-Myristoyltransferase (NMT), an enzyme that catalyses the covalent attachment of myristate to the N-terminal glycine of substrate proteins, has been described as a potential target for the treatment of this disease. Herein, we report the synthesis and the structure-guided optimization of a series of quinolines with balanced activity against both Plasmodium vivax and Plasmodium falciparum N-myristoyltransferase (NMT).
January 1, 2017: MedChemComm
https://www.readbyqxmd.com/read/28620583/engineering-of-genetically-arrested-parasites-gaps-for-a-precision-malaria-vaccine
#6
REVIEW
Oriana Kreutzfeld, Katja Müller, Kai Matuschewski
Continuous stage conversion and swift changes in the antigenic repertoire in response to acquired immunity are hallmarks of complex eukaryotic pathogens, including Plasmodium species, the causative agents of malaria. Efficient elimination of Plasmodium liver stages prior to blood infection is one of the most promising malaria vaccine strategies. Here, we describe different genetically arrested parasites (GAPs) that have been engineered in Plasmodium berghei, P. yoelii and P. falciparum and compare their vaccine potential...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28619120/g6pd-deficiency-alleles-in-a-malaria-endemic-region-in-the-western-brazilian-amazon
#7
Jamille G Dombrowski, Rodrigo M Souza, Jonathan Curry, Laura Hinton, Natercia R M Silva, Lynn Grignard, Ligia A Gonçalves, Ana Rita Gomes, Sabrina Epiphanio, Chris Drakeley, Jim Huggett, Taane G Clark, Susana Campino, Claudio R F Marinho
BACKGROUND: Plasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. This X-linked disorder is distributed globally and is caused by allelic variants with a geographical distribution that closely reflects populations exposed historically to endemic malaria...
June 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28619089/light-manipulation-of-mosquito-behaviour-acute-and-sustained-photic-suppression-of-biting-activity-in-the-anopheles-gambiae-malaria-mosquito
#8
Aaron D Sheppard, Samuel S C Rund, Gary F George, Erin Clark, Dominic J Acri, Giles E Duffield
BACKGROUND: Host-seeking behaviours in anopheline mosquitoes are time-of-day specific, with a greater propensity for nocturnal biting. We investigated how a short exposure to light presented during the night or late day can inhibit biting activity and modulate flight activity behaviour. RESULTS: Anopheles gambiae (s.s.), maintained on a 12:12 LD cycle, were exposed transiently to white light for 10-min at the onset of night and the proportion taking a blood meal in a human biting assay was recorded every 2 h over an 8-h duration...
June 16, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28619071/new-adenovirus-based-vaccine-vectors-targeting-pfs25-elicit-antibodies-that-inhibit-plasmodium-falciparum-transmission
#9
Kathleen A McGuire, Kazutoyo Miura, Christopher M Wiethoff, Kim C Williamson
BACKGROUND: An effective malaria transmission-blocking vaccine (TBV) would be a major advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies against Plasmodium falciparum surface protein, Pfs25, are known to block parasite development in the mosquito vector. However, in initial clinical trials the limited immunogenicity of recombinant Pfs25 protein-in-adjuvant vaccines has been a challenge. METHODS: Novel human adenovirus type 5 (Ad5) vectors were used in heterologous prime boost vaccination strategies to augment the immune response against Pfs25...
June 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28618269/red-blood-cell-invasion-by-the-malaria-parasite-is-coordinated-by-the-pfap2-i-transcription-factor
#10
Joana Mendonca Santos, Gabrielle Josling, Philipp Ross, Preeti Joshi, Lindsey Orchard, Tracey Campbell, Ariel Schieler, Ileana M Cristea, Manuel Llinás
Obligate intracellular parasites must efficiently invade host cells in order to mature and be transmitted. For the malaria parasite Plasmodium falciparum, invasion of host red blood cells (RBCs) is essential. Here we describe a parasite-specific transcription factor PfAP2-I, belonging to the Apicomplexan AP2 (ApiAP2) family, that is responsible for regulating the expression of genes involved in RBC invasion. Our genome-wide analysis by ChIP-seq shows that PfAP2-I interacts with a specific DNA motif in the promoters of target genes...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618199/lipid-interactions-modulate-the-structural-and-antigenic-properties-of-the-c-terminal-domain-of-the-malaria-antigen-merozoite-surface-protein-2
#11
Sreedam C Das, Rodrigo A V Morales, Jeffrey Seow, Krishnarjuna Bankala, Ravindu Dissanayake, Robin F Anders, Christopher A MacRaild, Raymond S Norton
Merozoite surface protein 2 (MSP2) is a highly abundant, GPI-anchored antigen on the malaria parasite Plasmodium falciparum. MSP2 induces an immune response in the context of natural infections and vaccine trials, and these responses are associated with protection from parasite infection. Recombinant MSP2 is highly disordered in solution but antigenic analyses suggest that it is more ordered on the merozoite surface. We have shown previously that the interaction of recombinant full-length MSP2 with lipid surfaces induces a conformational change in the conserved N-terminal region of MSP2, which contributes to epitope masking in this region...
June 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28617870/a-novel-genetic-technique-in-plasmodium-berghei-allows-liver-stage-analysis-of-genes-required-for-mosquito-stage-development-and-demonstrates-that-de-novo-heme-synthesis-is-essential-for-liver-stage-development-in-the-malaria-parasite
#12
Upeksha L Rathnapala, Christopher D Goodman, Geoffrey I McFadden
The combination of drug resistance, lack of an effective vaccine, and ongoing conflict and poverty means that malaria remains a major global health crisis. Understanding metabolic pathways at all parasite life stages is important in prioritising and targeting novel anti-parasitic compounds. The unusual heme synthesis pathway of the rodent malaria parasite, Plasmodium berghei, requires eight enzymes distributed across the mitochondrion, apicoplast and cytoplasm. Deletion of the ferrochelatase (FC) gene, the final enzyme in the pathway, confirms that heme synthesis is not essential in the red blood cell stages of the life cycle but is required to complete oocyst development in mosquitoes...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28617253/the-emerging-role-of-the-human-bone-marrow-as-a-privileged-developmental-niche-for-the-transmission-stages-of-the-malaria-parasite-plasmodium-falciparum-commentary
#13
Pietro Alano
The spread of malaria relies on the ability of the Plasmodium parasites to be transmitted from infected individuals to the Anopheles mosquito vectors. Recent work on the most lethal of the malaria parasites, Plasmodium falciparum, identified the infected human bone marrow as a preferential site for the localization and maturation of the parasite transmission stages, the gametocytes. These findings unveil a complex host parasite interplay and an unsuspected role of the bone marrow microenvironment in the successful transmission of the malaria parasite and have major implications in developing and targeting future interventions to block the transmission of P...
April 2017: Annali Dell'Istituto Superiore di Sanità
https://www.readbyqxmd.com/read/28615849/in-vivo-antimalarial-activity-of-aqueous-leaf-and-bark-extracts-of-trema-orientalis-against-plasmodium-berghei-in-mice
#14
Oluwatoyosi Eniola Oyebola, Olajumoke Abimbola Morenikeji, Isaiah Oluwafemi Ademola
The control of malaria relies on the use of chemical antimalarial, but the development of resistance necessitates research into alternatives. Trema orientalis (L.) Blume is used in Nigerian folklore medicine for the treatment of malaria. This study investigates the in vivo antiplasmodial activity of aqueous leaf and bark extracts of T. orientalis in rodent model. Swiss Albino mice weighing 23-27 g were intraperitoneally infected with Plasmodium berghei. The lethal dose in mice was estimated to be greater than 5000 mg/kg based on toxicity signs and death...
June 2017: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/28615061/synergistic-effect-of-il-12-and-il-18-induces-tim3-regulation-of-%C3%AE-%C3%AE-t-cell-function-and-decreases-the-risk-of-clinical-malaria-in-children-living-in-papua-new-guinea
#15
Louis Schofield, Lisa J Ioannidis, Stephan Karl, Leanne J Robinson, Qiao Y Tan, Daniel P Poole, Inoni Betuela, Danika L Hill, Peter M Siba, Diana S Hansen, Ivo Mueller, Emily M Eriksson
BACKGROUND: γδ T cells are important for both protective immunity and immunopathogenesis during malaria infection. However, the immunological processes determining beneficial or detrimental effects on disease outcome remain elusive. The aim of this study was to examine expression and regulatory effect of the inhibitory receptor T-cell immunoglobulin domain and mucin domain 3 (TIM3) on γδ T cells. While TIM3 expression and function on conventional αβ T cells have been clearly defined, the equivalent characterization on γδ T cells and associations with disease outcomes is limited...
June 15, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28615016/ex-vivo-susceptibility-and-genotyping-of-plasmodium-falciparum-isolates-from-pikine-senegal
#16
Aminata Mbaye, Amy Gaye, Baba Dieye, Yaye D Ndiaye, Amy K Bei, Muna Affara, Awa B Deme, Mamadou S Yade, Khadim Diongue, Ibrahima M Ndiaye, Tolla Ndiaye, Mouhamed Sy, Ngayo Sy, Ousmane Koita, Donald J Krogstad, Sarah Volkman, Davis Nwakanma, Daouda Ndiaye
BACKGROUND: The monitoring of Plasmodium falciparum sensitivity to anti-malarial drugs is a necessity for effective case management of malaria. This species is characterized by a strong resistance to anti-malarial drugs. In Senegal, the first cases of chloroquine resistance were reported in the Dakar region in 1988 with nearly 7% population prevalence, reaching 47% by 1990. It is in this context that sulfadoxine-pyrimethamine temporarily replaced chloroquine as first line treatment in 2003, pending the introduction of artemisinin-based combination therapy in 2006...
June 14, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28614791/human-vaccination-against-plasmodium-vivax-duffy-binding-protein-induces-strain-transcending-antibodies
#17
Ruth O Payne, Sarah E Silk, Sean C Elias, Kathryn H Milne, Thomas A Rawlinson, David Llewellyn, A Rushdi Shakri, Jing Jin, Geneviève M Labbé, Nick J Edwards, Ian D Poulton, Rachel Roberts, Ryan Farid, Thomas Jørgensen, Daniel Gw Alanine, Simone C de Cassan, Matthew K Higgins, Thomas D Otto, James S McCarthy, Willem A de Jongh, Alfredo Nicosia, Sarah Moyle, Adrian Vs Hill, Eleanor Berrie, Chetan E Chitnis, Alison M Lawrie, Simon J Draper
BACKGROUND: Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by the P. vivax merozoite depends on an interaction between the Duffy antigen receptor for chemokines (DARC) and region II of the parasite's Duffy-binding protein (PvDBP_RII). Naturally acquired binding-inhibitory antibodies against this interaction associate with clinical immunity, but it is unknown whether these responses can be induced by human vaccination...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28614050/cracking-ali-baba-s-code
#18
Oliver Billker
A protein called P36 holds the key to how different species of malaria parasite invade liver cells.
June 14, 2017: ELife
https://www.readbyqxmd.com/read/28612631/genetically-attenuated-malaria-parasites-as-vaccines
#19
Ashley M Vaughan, Stefan H I Kappe
No abstract text is available yet for this article.
June 16, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28612497/pharmacotherapy-follow-up-role-in-active-malaria-surveillance-in-a-travel-medicine-centre-outside-the-transmission-area-in-brazil
#20
R S Pedro, P Brasil, A Pina-Costa, C R Machado, L S Damasceno, C T Daniel-Ribeiro, L Guaraldo
WHAT IS KNOWN AND OBJECTIVE: Malaria is a potentially severe disease, widespread in tropical and subtropical areas. Apart from parasite drug resistance, which receives the largest share of attention, several factors directly influence the response to antimalarial treatment such as incorrect doses, adverse drug events, lack of adherence to treatment, drug quality and drug-drug interactions. Pharmacotherapy follow-up can be used to monitor and improve the effectiveness of treatment, prevent drug-related problems and ensure patient safety...
June 13, 2017: Journal of Clinical Pharmacy and Therapeutics
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