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https://www.readbyqxmd.com/read/28639657/exploring-the-catalytic-mechanism-of-dihydropteroate-synthase-elucidating-the-differences-between-the-substrate-and-inhibitor
#1
Warot Chotpatiwetchkul, Kanokthip Boonyarattanakalin, Duangkamol Gleeson, M Paul Gleeson
Dihydropteroate synthase (DHPS) catalyzes the condensation of 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (DHPPP) with p-aminobenzoic acid (pABA) and is a well validated target for anti-malarial and anti-bacterial drugs. However, in recent years its utility as a therapeutic target has diminished considerably due to multiple mutations. As such, considerable structural biology and medicinal chemistry effort has been expended to understand and overcome this issue. To date no detailed computational analysis of the protein mechanism has been made despite the detailed crystal structures and multiple mechanistic proposals being made...
June 22, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28595540/apicoplast-import-protein-tic20-a-promising-therapeutic-molecular-target-for-plasmodium-falciparum-an-insilico-approach-for-therapeutic-intervention
#2
Pavan C P K Srimath-Tirumala-Peddinti, Sandeep Solmon Kusuma, Deepthi Nammi, Nageswara Rao Reddy Neelapu
Malaria is a lethal disease causing mortality to over millions each year. Drug resistance in the malarial parasite encouraged to discover effective antimalarial drug targets and drugs. An objective of this current study is to identify drug targets for malarial parasite. Genes unique, non-homologous to humans and essential for parasite are identified using BLASTn by comparing genomes between parasite and host. Further open BLASTp was used to filter the targets specific to Plasmodium species and later were subjected to gene property analysis to identify 65 potential targets...
June 5, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28569315/enhancing-the-sensing-specificity-of-a-mos2-nanosheet-based-fret-aptasensor-using-a-surface-blocking-strategy
#3
Alisha Geldert, Kenry, Xiao Zhang, Hua Zhang, Chwee Teck Lim
Aptamer-based biosensing, which uses short, single-stranded nucleic acid segments to bind to a target, can be advantageous over antibody-based diagnostics due to the ease of synthesis and high stability of aptamers. However, the development of most aptamer-based sensors (aptasensors) is still in its initial stages and many factors affecting their performance have not been studied in great detail. Here, we enhance the sensing specificity of a fluorescence resonance energy transfer (FRET)-based MoS2 nanosheet aptasensor in detecting the malarial biomarker Plasmodium lactate dehydrogenase (pLDH)...
June 1, 2017: Analyst
https://www.readbyqxmd.com/read/28555033/annual-wormwood-leaf-inhibits-the-adipogenesis-of-3t3-l1-and-obesity-in-high-fat-diet-induced-obese-rats
#4
Yuno Song, Soo-Jung Lee, Sun-Hee Jang, Tae Hoon Kim, Hong-Duck Kim, Sung-Woo Kim, Chung-Kil Won, Jae-Hyeon Cho
Annual wormwood (AW) (Artemisia annua L.) has anti-malarial, anti-bacterial, anti-oxidant, anti-tumour, and anti-inflammatory activities. In the present study, we evaluated the effects of annual wormwood leaves (AWL) on adipocyte differentiation in 3T3-L1 cells and high-fat diet (HFD)-induced obese rats. 3T3-L1 adipocytes and HFD-induced obese rats were treated with AWL, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. Treatment with AWL effectively prevented triglyceride accumulation during adipogenesis in a dose-dependent manner...
May 28, 2017: Nutrients
https://www.readbyqxmd.com/read/28500788/unraveling-the-importance-of-the-malaria-parasite-helicases
#5
REVIEW
Renu Tuteja
Malaria is a human parasitic disease caused by infection from Plasmodium species, particularly Plasmodium falciparum. Each year millions of people are infected with malaria and large numbers of deaths result due to this deadly infection. P. falciparum contains 14 chromosomes, nearly 5400 genes and a multistage life cycle in humans and mosquitoes. The control of malaria is still a challenge as the parasite is continuously developing resistance to available anti-malarial drugs and the mosquito vector is developing resistance to insecticides...
May 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28422980/genetic-and-epigenetic-changes-in-host-abcb1-influences-malaria-susceptibility-to-plasmodium-falciparum
#6
Himanshu Gupta, Sima Chaudhari, Ayushi Rai, Smitha Bhat, Pratima K Sahu, Manjunath H Hande, Sydney C D'Souza, Umakanth Shashikiran, Kapaettu Satyamoorthy
Multiple mechanisms such as genetic and epigenetic variations within a key gene may play a role in malarial susceptibility and response to anti-malarial drugs in the population. ABCB1 is one of the well-studied membrane transporter genes that code for the P-glycoprotein (an efflux protein) and whose effect on malaria disease predisposition and susceptibility to drugs remains to be understood. We studied the association of single nucleotide variations in human ABCB1 that influences its function in subjects with uncomplicated and complicated malaria caused by Plasmodium falciparum (Pf)...
2017: PloS One
https://www.readbyqxmd.com/read/28369062/t-cell-subtypes-and-reciprocal-inflammatory-mediator-expression-differentiate-p-falciparum-memory-recall-responses-in-asymptomatic-and-symptomatic-malaria-patients-in-southeastern-haiti
#7
Jason S Lehmann, Joseph J Campo, Micheline Cicéron, Christian P Raccurt, Jacques Boncy, Valery E M Beau De Rochars, Anthony P Cannella
Asymptomatic Plasmodium falciparum infection is responsible for maintaining malarial disease within human populations in low transmission countries such as Haiti. Investigating differential host immune responses to the parasite as a potential underlying mechanism could help provide insight into this highly complex phenomenon and possibly identify asymptomatic individuals. We performed a cross-sectional analysis of individuals who were diagnosed with malaria in Sud-Est, Haiti by comparing the cellular and humoral responses of both symptomatic and asymptomatic subjects...
2017: PloS One
https://www.readbyqxmd.com/read/28368498/the-antigen-presenting-potential-of-v%C3%AE-9v%C3%AE-2-t-cells-during-plasmodium-falciparum-blood-stage-infection
#8
Jennifer Howard, Séverine Loizon, Christopher J Tyler, Dorothée Duluc, Bernhard Moser, Matthieu Mechain, Alexandre Duvignaud, Denis Malvy, Marita Troye-Blomberg, Jean-Francois Moreau, Matthias Eberl, Odile Mercereau-Puijalon, Julie Déchanet-Merville, Charlotte Behr, Maria Mamani-Matsuda
During Plasmodium falciparum infections, erythrocyte-stage parasites inhibit dendritic cell maturation and function, compromising effective antimalarial adaptive immunity. Human Vγ9Vδ2 T cells can act in vitro as antigen-presenting cells (APCs) and induce αβ T-cell activation. However, the relevance of this activity in vivo has remained elusive. Because Vγ9Vδ2 T cells are activated during the early immune response against P. falciparum infection, we investigated whether they could contribute to the instruction of adaptive immune responses toward malaria parasites...
May 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28357359/chemical-proteomics-approach-reveals-the-direct-targets-and-the-heme-dependent-activation-mechanism-of-artemisinin-in-plasmodium-falciparum-using-an-artemisinin-based-activity-probe
#9
COMMENT
Jigang Wang, Qingsong Lin
Artemisinin and its analogues are currently the most effective anti-malarial drugs. The activation of artemisinin requires the cleavage of the endoperoxide bridge in the presence of iron sources. Once activated, artemisinins attack macromolecules through alkylation and propagate a series of damages, leading to parasite death. Even though several parasite proteins have been reported as artemisinin targets, the exact mechanism of action (MOA) of artemisinin is still controversial and its high potency and specificity against the malaria parasite could not be fully accounted for...
April 5, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28357319/phylogenetic-profiles-of-all-membrane-transport-proteins
#10
January Weiner, Taco W A Kooij
In order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. Proteins that are essential to survival and specific to malaria parasites are key candidates. To survive within host cells, the parasites need to acquire nutrients and dispose of waste products across multiple membranes. Additionally, like all eukaryotes, they must redistribute ions and organic molecules between their various internal membrane bound compartments. Membrane transport proteins mediate all of these processes and are considered important mediators of drug resistance as well as drug targets in their own right...
August 30, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28340585/analytical-sensitivity-of-current-best-in-class-malaria-rapid-diagnostic-tests
#11
COMPARATIVE STUDY
Alfons Jimenez, Roxanne R Rees-Channer, Rushini Perera, Dionicia Gamboa, Peter L Chiodini, Iveth J González, Alfredo Mayor, Xavier C Ding
BACKGROUND: Rapid diagnostic tests (RDTs) are today the most widely used method for malaria diagnosis and are recommended, alongside microscopy, for the confirmation of suspected cases before the administration of anti-malarial treatment. The diagnostic performance of RDTs, as compared to microscopy or PCR is well described but the actual analytical sensitivity of current best-in-class tests is poorly documented. This value is however a key performance indicator and a benchmark value needed to developed new RDTs of improved sensitivity...
March 24, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28320390/false-negative-malaria-rapid-diagnostic-tests-in-rwanda-impact-of-plasmodium-falciparum-isolates-lacking-hrp2-and-declining-malaria-transmission
#12
Christina T Kozycki, Noella Umulisa, Stephen Rulisa, Emil I Mwikarago, Jean Pierre Musabyimana, Jean Pierre Habimana, Corine Karema, Donald J Krogstad
BACKGROUND: Rapid diagnostic tests (RDTs) for histidine rich protein 2 (HRP2) are often used to determine whether persons with fever should be treated with anti-malarials. However, Plasmodium falciparum parasites with a deletion of the hrp2 gene yield false-negative RDTs and there are concerns the sensitivity of HRP2-based RDTs may fall when the intensity of transmission decreases. METHODS: This observational study enrolled 9226 patients at three health centres in Rwanda from April 2014 to April 2015...
March 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28292906/parasitophorous-vacuole-poration-precedes-its-rupture-and-rapid-host-erythrocyte-cytoskeleton-collapse-in-plasmodium-falciparum-egress
#13
Victoria L Hale, Jean M Watermeyer, Fiona Hackett, Gema Vizcay-Barrena, Christiaan van Ooij, James A Thomas, Matthew C Spink, Maria Harkiolaki, Elizabeth Duke, Roland A Fleck, Michael J Blackman, Helen R Saibil
In the asexual blood stages of malarial infection, merozoites invade erythrocytes and replicate within a parasitophorous vacuole to form daughter cells that eventually exit (egress) by sequential rupture of the vacuole and erythrocyte membranes. The current model is that PKG, a malarial cGMP-dependent protein kinase, triggers egress, activating malarial proteases and other effectors. Using selective inhibitors of either PKG or cysteine proteases to separately inhibit the sequential steps in membrane perforation, combined with video microscopy, electron tomography, electron energy loss spectroscopy, and soft X-ray tomography of mature intracellular Plasmodium falciparum parasites, we resolve intermediate steps in egress...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28283009/-production-and-molecular-characterization-of-plasmodium-falciparum-recombinant-circumsporozoite-protein-with-37-nanp-and-4-nvdp-epitopes
#14
Yunus Uyar, Abdüssamed Akşit, Serkan Karaca, Şirin Sahra Ceylan, Merve Yürük
Malaria is caused by the protozoan parasite Plasmodium, the leading cause of death amongst the parasitic diseases. The disease is transmitted to human by the bites of female Anopheles mosquitoes. According to the World Health Organization (WHO) data, there were an estimated 214 million malaria cases and estimated 438.000 deaths occurred worldwide, in 2015. It is observed that 90% of all the deaths due to malaria occur in Africa. 78% of these cases were children who are under five years old. Intensive malaria interventions helped to reduce malaria incidence by 37% between 2000 and 2015...
January 2017: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28270152/a-systematic-review-on-malaria-sero-epidemiology-studies-in-the-brazilian-amazon-insights-into-immunological-markers-for-exposure-and-protection
#15
REVIEW
Pedro M Folegatti, André M Siqueira, Wuelton M Monteiro, Marcus Vinícius G Lacerda, Chris J Drakeley, Érika M Braga
BACKGROUND: Considerable success in reducing malaria incidence and mortality has been achieved in Brazil, leading to discussions over the possibility of moving towards elimination. However, more than reporting and counting clinical cases, elimination will require the use of efficient tools and strategies for measuring transmission dynamics and detecting the infectious reservoir as the primary indicators of interest for surveillance and evaluation. Because acquisition and maintenance of anti-malarial antibodies depend on parasite exposure, seroprevalence rates could be used as a reliable tool for assessing malaria endemicity and an adjunct measure for monitoring transmission in a rapid and cost-effective manner...
March 7, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28258239/the-pushmi-pullyu-of-resistance-to-chloroquine-in-malaria
#16
REVIEW
Ruth Skrzypek, Richard Callaghan
Malarial infection continues to impart devastating health problems in the developing world. Treatment of malaria has involved chemotherapy since 168 BC, with the most prevalent and successful forms using plant alkaloids. Perhaps the greatest treatment success against malaria was by chloroquine, a synthetic derivative of the quinines found in the Cinchona tree bark. Chloroquine is able to kill parasites by interfering with haem metabolism in the parasite's digestive vacuole. The widespread use of chloroquine predictably resulted in the development of drug-resistant malaria and the most highly implicated resistance mediators are the transporter proteins P-glycoprotein (P-gp) homologue 1 (P-gh1) and Plasmodium falciparum chloroquine-resistance transporter (PfCRT), which reside on the parasite's digestive vacuole...
February 28, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28252130/an-embedded-barcode-for-connected-malaria-rapid-diagnostic-tests
#17
Thomas F Scherr, Sparsh Gupta, David W Wright, Frederick R Haselton
Many countries are shifting their efforts from malaria control to disease elimination. New technologies will be necessary to meet the more stringent demands of elimination campaigns, including improved quality control of malaria diagnostic tests, as well as an improved means for communicating test results among field healthcare workers, test manufacturers, and national ministries of health. In this report, we describe and evaluate an embedded barcode within standard rapid diagnostic tests as one potential solution...
March 2, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28242687/quantification-of-labile-heme-in-live-malaria-parasites-using-a-genetically-encoded-biosensor
#18
James R Abshire, Christopher J Rowlands, Suresh M Ganesan, Peter T C So, Jacquin C Niles
Heme is ubiquitous, yet relatively little is known about the maintenance of labile pools of this cofactor, which likely ensures its timely bioavailability for proper cellular function. Quantitative analysis of labile heme is of fundamental importance to understanding how nature preserves access to the diverse chemistry heme enables, while minimizing cellular damage caused by its redox activity. Here, we have developed and characterized a protein-based sensor that undergoes fluorescence quenching upon heme binding...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28195463/target-elucidation-by-cocrystal-structures-of-nadh-ubiquinone-oxidoreductase-of-plasmodium-falciparum-pfndh2-with-small-molecule-to-eliminate-drug-resistant-malaria
#19
Yiqing Yang, You Yu, Xiaolu Li, Jing Li, Yue Wu, Jie Yu, Jingpeng Ge, Zhenghui Huang, Lubin Jiang, Yu Rao, Maojun Yang
Drug-resistant malarial strains have been continuously emerging recently, which posts a great challenge for the global health. Therefore, new antimalarial drugs with novel targeting mechanisms are urgently needed for fighting drug-resistant malaria. NADH-ubiquinone oxidoreductase of Plasmodium falciparum (PfNDH2) represents a viable target for antimalarial drug development. However, the absence of structural information on PfNDH2 limited rational drug design and further development. Herein, we report high resolution crystal structures of the PfNDH2 protein for the first time in Apo-, NADH-, and RYL-552 (a new inhibitor)-bound states...
February 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28188731/design-in-silico-and-in%C3%A2-vitro-evaluation-of-curcumin-analogues-against-plasmodium-falciparum
#20
Chandrajit Dohutia, Dipak Chetia, Kabita Gogoi, Kishore Sarma
The polyphenolic compound curcumin has been reported for its antimalarial properties in various scientific studies. Plasmodium falciparum ATP6, the parasite orthologue of mammalian sarcoplasmic Ca(2+) ATPase (SERCA) has been identified as a key molecular target of both artemisinin and curcumin. The work was thereby undertaken to study the anti-malarial properties of two different series of curcumin analogues based on their docking interactions with PfATP6 and correlating the results with their anti-malarial activity...
April 2017: Experimental Parasitology
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