Publications

amodiaquine analogues containing no-donor substructures: synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria.	the synthesis and physico-chemical properties of novel compounds obtained by conjugation of amodiaquine with moieties containing either furoxan or nitrooxy no-donor substructures are described. the synthesised compounds were tested in vitro against both the chloroquine sensitive, d10 and the chloroquine resistant, w-2 strains of plasmodium falciparum (p. falciparum). most of the compounds showed an antiplasmodial activity comparable to that of the parent drug. by comparing the activities of simp ...	2011	21396743
synthesis of benzologues of nitazoxanide and tizoxanide: a comparative study of their in vitro broad-spectrum antiprotozoal activity.	we have synthesized two new benzologues of nitazoxanide (nit) and tizoxanide (tiz), using a short synthetic route. both compounds were tested in vitro against six protozoa (giardia intestinalis, trichomonas vaginalis, entamoeba histolytica, plasmodium berghei, leishmania mexicana and trypanosoma cruzi). compound 1 (benzologue of nit) showed broad antiprotozoal effect against all parasites tested, showing ic(50)'s<5 ++m. this compound was five-times more active than nit, and 18-times more potent ...	2011	21397502
suppression of plasmodium berghei parasitemia by licl in an animal infection model.	malaria, caused by the plasmodium parasite is still a health problem worldwide due to resistance of the pathogen to current anti-malarials. the search for new anti-malarial agents has become more crucial with the emergence of chloroquine-resistant plasmodium falciparum strains. protein kinases such as mitogen-activated protein kinase (mapk), mapk kinase, cyclin-dependent kinase (cdk) and glycogen synthase kinase- 3(gsk-3) of parasitic protozoa are potential drug targets. gsk-3 is an enzyme that ...	2010	21399604
use of a selective inhibitor to define the chemotherapeutic potential of the plasmodial hexose transporter in different stages of the parasite's life cycle.	during blood infection, malarial parasites use d-glucose as their main energy source. the plasmodium falciparum hexose transporter (pfht), which mediates the uptake of d-glucose into parasites, is essential for survival of asexual blood-stage parasites. recently, genetic studies in the rodent malaria model, plasmodium berghei, found that the orthologous hexose transporter (pbht) is expressed throughout the parasite's development within the mosquito vector, in addition to being essential during i ...	2011	21402842
sex and death: the effects of innate immune factors on the sexual reproduction of malaria parasites.	malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria ...	2011	21408620
disturbance in hemoglobin metabolism and in vivo antimalarial activity of azole antimycotics.	plasmodium parasites degrade host hemoglobin to obtain free amino acids, essential for protein synthesis. during this event, free toxic heme moieties crystallize spontaneously to produce a non-toxic pigment called hemozoin or ß-hematin. in this context, a group of azole antimycotics, clotrimazole (ctz), ketoconazole (ktz) and fluconazole (fcz), were investigated for their abilities to inhibit ß-hematin synthesis (ißhs) and hemoglobin proteolysis (ihbp) in vitro. the ß-hematin synthesis was recor ...	2011	21412616
nitric oxide protection against murine cerebral malaria is associated with improved cerebral microcirculatory physiology.	cerebral malaria (cm) is a leading cause of death in plasmodium falciparum infections. in the plasmodium berghei anka (pba) murine model, cm pathogenesis is associated with low nitric oxide (no) bioavailability and brain microcirculatory complications, with a marked decrease in cerebral blood flow, vasoconstriction, vascular plugging by adherent cells, and hemorrhages. using intravital microscopy through a closed cranial window, here we show that no supplementation in the form of a no donor (dip ...	2011	21415018
development of the piggybac transposable system for plasmodium berghei and its application for random mutagenesis in malaria parasites.	the genome of a number of species of malaria parasites (plasmodium spp.) has been sequenced in the hope of identifying new drug and vaccine targets. however, almost one-half of predicted plasmodium genes are annotated as hypothetical and are difficult to analyse in bulk due to the inefficiency of current reverse genetic methodologies for plasmodium. recently, it has been shown that the transposase piggybac integrates at random into the genome of the human malaria parasite p. falciparum offering ...	2011	21418605
differential microrna expression in experimental cerebral and noncerebral malaria.	micrornas (mirnas) are posttranscriptional regulatory molecules that have been implicated in the regulation of immune responses, but their role in the immune response to plasmodium infection is unknown. we studied the expression of selected mirnas following infection of cba mice with plasmodium berghei anka (pba), which causes cerebral malaria (cm), or plasmodium berghei k173 (pbk), which causes severe malaria but without cerebral complications, termed non-cm. the differential expression profile ...	2011	21422175
aminoindoles, a novel scaffold with potent activity against plasmodium falciparum.	this study characterizes aminoindole molecules that are analogs of genz-644442. genz-644442 was identified as a hit in a screen of ~70,000 compounds in the broad institute's small-molecule library and the iccb-l compound collection at harvard medical school. genz-644442 is a potent inhibitor of plasmodium falciparum in vitro (50% inhibitory concentrations [ic50s], 200 to 285 nm) and inhibits p. berghei in vivo with an efficacy of > 99% in an adapted version of peters' 4-day suppressive test (w. ...	2011	21422215
plasmodium berghei anka infection increases foxp3, il-10 and il-2 in cxcl-10 deficient c57bl/6 mice.	cerebral malaria (cm) is a major cause of malaria mortality. sequestration of infected red blood cells and leukocytes in brain vessels coupled with the production of pro-inflammatory factors contribute to cm. cxcl-10 a chemokine that is chemotactic to t cells has been linked to fatal cm. mice deficient for cxcl-10 gene are resistant to murine cm, while antibody ablation of cxcl-10 enhanced the production of regulatory t cells (cd4+cd25+foxp3+) and il-10 which regulate the immune system. interleu ...	2011	21439091
induction of antimalaria immunity by pyrimethamine prophylaxis during exposure to sporozoites is curtailed by parasite resistance.	each year, infections with the protozoan parasite plasmodium falciparum kill 1 million people, mostly children in africa. intermittent preventive treatment (ipt) with sulfadoxine-pyrimethamine (sp) reduces the incidence of malaria and aims to prevent mortality in infants, children, and pregnant women. there is contradictory evidence as to whether this strategy may generate additional protection against reinfection beyond the limited duration of the intervention. previous work established that ab ...	2011	21444698
dendritic cells and hepatocytes use distinct pathways to process protective antigen from plasmodium in vivo.	malaria-protective cd8+ t cells specific for the circumsporozoite (cs) protein are primed by dendritic cells (dcs) after sporozoite injection by infected mosquitoes. the primed cells then eliminate parasite liver stages after recognizing the cs epitopes presented by hepatocytes. to define the in vivo processing of cs by dcs and hepatocytes, we generated parasites carrying a mutant cs protein containing the h-2k(b) epitope siinfekl, and evaluated the t cell response using transgenic and mutant mi ...	2011	21445239
plasmodium cysteine repeat modular proteins 3 and 4 are essential for malaria parasite transmission from the mosquito to the host.	the plasmodium cysteine repeat modular proteins (pcrmp) are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. analysis of mutants of the rodent parasite plasmodium berghei lacking expression of pcrmp1 or 2 showed that these proteins are essential for targeting of p. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse.	2011	21453484
simple flow cytometric detection of haemozoin containing leukocytes and erythrocytes for research on diagnosis, immunology and drug sensitivity testing.	malaria pigment (haemozoin, hz) has been the focus of diverse research efforts. however, identification of hz-containing leukocytes or parasitized erythrocytes is usually based on microscopy, with inherent limitations. flow cytometric detection of depolarized side-scatter is more accurate and its adaptation to common bench top flow cytometers might allow several applications. these can range from the ex-vivo and in-vitro detection and functional analysis of hz-containing leukocytes to the detect ...	2011	21453521
toward forward genetic screens in malaria-causing parasites using the piggybac transposon.	the ability to analyze gene function in malaria-causing plasmodium parasites has received a boost with a recent paper in bmc genomics that describes a genome-wide mutagenesis system in the rodent malaria species plasmodium berghei using the transposon piggybac. this advance holds promise for identifying and validating new targets for intervention against malaria. but further improvements are still needed for the full power of genome-wide molecular genetic screens to be utilized in this organism. ...	2011	21453557
plasmodium-host interactions directly influence the threshold of memory cd8 t cells required for protective immunity.	plasmodium infections are responsible for millions of cases of malaria and ~1 million deaths annually. recently, we showed that sterile protection (95%) in balb/c mice required plasmodium berghei circumsporozoite protein (cs(252-260))-specific memory cd8 t cells exceeding a threshold of 1% of all pbls. importantly, it is not known if plasmodium species affect the threshold of cs-specific memory cd8 t cells required for protection. furthermore, c57bl/6 mice immunized with radiation-attenuated par ...	2011	21460205
experimental asexual blood stage malaria immunity.	immunity to asexual blood stages of malaria is complex, involving both humoral and cell-mediated immune mechanisms. the availability of murine models of malaria has greatly facilitated the analysis of immune mechanisms involved in resistance to the asexual blood stages. this unit details the materials and methods required for inducing protective immunity toward experimental blood stage malaria parasites by vaccination, repeated infection, and drug cure, as well as adoptive transfer of antigen-sp ...	2011	21462169
cd8+ t cells and ifn-γ mediate the time-dependent accumulation of infected red blood cells in deep organs during experimental cerebral malaria.	infection with plasmodium berghei anka (pba) in susceptible mice induces a syndrome called experimental cerebral malaria (ecm) with severe pathologies occurring in various mouse organs. immune mediators such as t cells or cytokines have been implicated in the pathogenesis of ecm. red blood cells infected with pba parasites have been shown to accumulate in the brain and other tissues during infection. this accumulation is thought to be involved in pba-induced pathologies, which mechanisms are poo ...	2011	21494565
antimalarial activity of endoperoxide compound 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol.	plasmodium falciparum, the major causative parasite for the disease, has acquired resistance to most of the antimalarial drugs used today, presenting an immediate need for new antimalarial drugs. here, we report the in vitro and in vivo antimalarial activities of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (n-251) against p. falciparum and plasmodium berghei parasites. the n-251 showed high antimalarial potencies both in the in vitro and the in vivo tests (ec(50) 2.3×10(-8) m; ed(50) 1 ...	2011	21501696
lead optimization of aryl and aralkyl amine-based triazolopyrimidine inhibitors of plasmodium falciparum dihydroorotate dehydrogenase with antimalarial activity in mice.	malaria is one of the leading causes of severe infectious disease worldwide; yet, our ability to maintain effective therapy to combat the illness is continually challenged by the emergence of drug resistance. we previously reported identification of a new class of triazolopyrimidine-based plasmodium falciparum dihydroorotate dehydrogenase (pfdhodh) inhibitors with antimalarial activity, leading to the discovery of a new lead series and novel target for drug development. active compounds from the ...	2011	21517059
multiple roles for plasmodium berghei phosphoinositide-specific phospholipase c in regulating gametocyte activation and differentiation.	critical events in the life cycle of malaria parasites are controlled by calcium-dependent signalling cascades, yet the molecular mechanisms of calcium release remain poorly understood. the synchronized development of plasmodium berghei gametocytes relies on rapid calcium release from internal stores within 10 s of gametocytes being exposed to mosquito-derived xanthurenic acid (xa). here we addressed the function of phosphoinositide-specific phospholipase c (pi-plc) for regulating gametocyte act ...	2011	21518218
sickle hemoglobin confers tolerance to plasmodium infection.	sickle human hemoglobin (hb) confers a survival advantage to individuals living in endemic areas of malaria, the disease caused by plasmodium infection. as demonstrated hereby, mice expressing sickle hb do not succumb to experimental cerebral malaria (ecm). this protective effect is exerted irrespectively of parasite load, revealing that sickle hb confers host tolerance to plasmodium infection. sickle hb induces the expression of heme oxygenase-1 (ho-1) in hematopoietic cells, via a mechanism in ...	2011	21529713
structure-function analysis of the anopheles gambiae lrim1/apl1c complex and its interaction with complement c3-like protein tep1.	malaria threatens half the world's population and exacts a devastating human toll. the principal malaria vector in africa, the mosquito anopheles gambiae, encodes 24 members of a recently identified family of leucine-rich repeat proteins named lrims. two members of this family, lrim1 and apl1c, are crucial components of the mosquito complement-like pathway that is important for immune defense against plasmodium parasites. lrim1 and apl1c circulate in the hemolymph exclusively as a disulfide-bond ...	2011	21533217
selection of drug resistant mutants from random library of plasmodium falciparum dihydrofolate reductase in plasmodium berghei model.	abstract:	2011	21554743
s1p is associated with protection in human and experimental cerebral malaria.	cerebral malaria (cm) is associated with excessive inflammatory responses and endothelial activation. sphingosine 1-phosphate (s1p) is a signaling sphingolipid implicated in regulating vascular integrity, inflammation and t cell migration. we hypothesized that altered s1p signaling during malaria contributes to endothelial activation and inflammation, and show that plasma s1p levels were decreased in ugandan children with cm compared to children with uncomplicated malaria. using the plasmodium b ...	2011	21556483
functional genetics in apicomplexa: potentials and limits.	the apicomplexans are obligate intracellular protozoan parasites and the causative agents of severe diseases in humans and animals. although complete genome sequences are available since many years and for several parasites, they are replete with putative genes of unassigned function. forward and reverse genetic approaches are limited only to a few apicomplexans that can either be propagated in vitro or in a convenient animal model. this review will compare and contrast the most recent strategie ...	2011	21557944
natural microbe-mediated refractoriness to plasmodium infection in anopheles gambiae.	malaria parasite transmission depends on the successful transition of plasmodium through discrete developmental stages in the lumen of the mosquito midgut. like the human intestinal tract, the mosquito midgut contains a diverse microbial flora, which may compromise the ability of plasmodium to establish infection. we have identified an enterobacter bacterium isolated from wild mosquito populations in zambia that renders the mosquito resistant to infection with the human malaria parasite plasmodi ...	2011	21566196
a new role for an old antimicrobial: lysozyme c-1 can function to protect malaria parasites in anopheles mosquitoes.	plasmodium requires an obligatory life stage in its mosquito host. the parasites encounter a number of insults while journeying through this host and have developed mechanisms to avoid host defenses. lysozymes are a family of important antimicrobial immune effectors produced by mosquitoes in response to microbial challenge.	2011	21573077
fosmidomycin uptake into plasmodium and babesia-infected erythrocytes is facilitated by parasite-induced new permeability pathways.	highly charged compounds typically suffer from low membrane permeability and thus are generally regarded as sub-optimal drug candidates. nonetheless, the highly charged drug fosmidomycin and its more active methyl-derivative fr900098 have proven parasiticidal activity against erythrocytic stages of the malaria parasite plasmodium falciparum. both compounds target the isoprenoid biosynthesis pathway present in bacteria and plastid-bearing organisms, like apicomplexan parasites. surprisingly, the ...	2011	21573242
a new class of phenazines with activity against a chloroquine resistant plasmodium falciparum strain and antimicrobial activity.	a series of new phenazines was synthesized by oxygenation of 1- and 2-naphthol with transition metal peroxo complexes and in situ reaction with 1,2-diamines. the phenazines 7-10 and 17 and 18 were derived from the corresponding 1,2-naphthoquinones, compounds 11-14, 19-25, 27-29, 31, and 32 from the corresponding "dimeric" 1,2-naphthoquinones and phenazines 33, 37, and 41 from related 1,2-diones or 1,4 diones. the title compounds were evaluated for in vitro antimalarial activity against plasmodiu ...	2011	21591758
anti-malarial effect of gum arabic.	abstract: background: gum arabic (ga), a nonabsorbable nutrient from the exudate of acacia senegal, exerts a powerful immunomodulatory effect on dendritic cells, antigen-presenting cells involved in the initiation of both innate and adaptive immunity. on the other hand ga degradation delivers short chain fatty acids, which in turn have been shown to foster the expression of foetal haemoglobin in erythrocytes. increased levels of erythrocyte foetal haemoglobin are known to impede the intraerythro ...	2011	21599958
effects of plasmodium berghei on thymus: high levels of apoptosis and premature egress of cd4(+)cd8(+) thymocytes in experimentally infected mice.	we have previously showed alterations in the thymus during experimental infection with plasmodium berghei, the causative agent of malaria. such alterations comprised histological changes with loss of delimitation between cortical and medullar regions, a profound atrophy with depletion of cd4(+)cd8(+) double-positive (dp) thymocytes, and severe changes in the expression of cell migration-related molecules, belonging to the extracellular matrix and chemokine protein families. taken together, these ...	2011	21601941
plasmodium berghei induces apoptotic changes in splenic and peripheral blood cells.	intracellular parasites manipulate host cell apoptosis in different ways either to increase their life span within infected cells or to spread infection. the present data provided information on the cellular changes taking place in spleen and peripheral blood during plasmodium berghei-infection and indicated apoptosis mediated host immune response during infection. our results suggested a significant change in cellular composition and absolute number of white blood cells in spleen and peripheral ...	2011	21602777
induction of pro-inflammatory mediators in plasmodium berghei infected balb/c mice breaks blood-brain-barrier and leads to cerebral malaria in an il-12 dependent manner.	a severe complication of plasmodium infection is cerebral malaria, a condition mainly attributed to overwhelming inflammatory immune reactions of the host. murine models differing in susceptibility to experimental cerebral malaria (ecm) allow detailed studies of the host response. we show that ecm- resistant balb/c mice were driven into interferon gamma- and il-12-dependent ecm and subsequent death if they received cpg-oligonucleotides after plasmodium berghei anka (pba) infection. cpg applicati ...	2011	21609776
synthesis and biological screening of some pyridine derivatives as anti-malarial agents.	two series of pyridine derivatives were synthesised and evaluated for their in vivo anti-malarial activity against plasmodium berghei. the anti-malarial activity was determined in vivo by applying 4-day standard suppressive test using chloroquine (cq)-sensitive p. berghei anka strain-infected mice. compounds 2a, 2g and 2h showed inhibition of the parasite multiplication by 90, 91 and 80%, respectively, at a dose level of 50 µmol/kg. moreover, the most active compounds (2a, 2g and 2h) were tested ...	2011	21612373
plasmodium berghei proteome changes in response to ssj-183 treatment.	the benzo[a]phenoxazine derivative, ssj-183 has shown excellent anti-malarial efficacy and safety. however, its mechanism of action is unclear. we investigated the effect of ssj-183 on the rodent malarial parasite, plasmodium berghei. we analyzed changes in protein expression in the erythrocytic cycle of p. berghei with or without 18h of ssj-183 treatment by two-dimensional gel electrophoresis. we confirmed results with matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flig ...	2011	21622001
transition of plasmodium sporozoites into liver stage-like forms is regulated by the rna binding protein pumilio.	many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve rna binding proteins as regulators of translation of key mrnas. in malaria parasites (plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. ...	2011	21625527
synthesis and antimalarial activity of 2-guanidino-4-oxoimidazoline derivatives.	a series of 2-guanidino-4-oxoimidazoline (deoxo-iz) derivatives was prepared and showed potent antimalarial activities in rodent and rhesus models. compound 8e, the most potent analogues of this series, is the first non-8-aminoqinoline antimalarial that demonstrated radical curative activity in non-human primate by oral route and showed causal prophylactic activity comparable to that of the commonly used clinical drugs in rhesus monkeys infected with sporozoites of plasmodium cynomolgi. the meta ...	2011	21627120
antimalarial pyrido[1,2-a]benzimidazoles.	a novel class of antimalarial pyrido[1,2-a]benzimidazoles were synthesized and evaluated for antiplasmodial activity and cytotoxicity following hits identified from screening commercially available compound collections. the most active of these, tdr86919 (4c), showed improved in vitro activity v the drug-resistant k1 strain of plasmodium falciparum relative to chloroquine (ic50 = 0.047 µm v 0.17 µm); potency was retained against a range of drug-sensitive and drug-resistant strains, with negligib ...	2011	21644541
imidazolopiperazines (i): optimization for new antimalarial agents.	starting from a hit series from a gnf compound library collection and based on a cell-based proliferation assay of plasmodium falciparum, a novel imidazolopiperazine scaffold was optimized. sar for this series of compounds is discussed, focusing on optimization of cellular potency against wild-type and drug resistant parasites and improvement of physiochemical and pharmacokinetic properties. the lead compounds in this series showed good potencies in vitro and decent oral exposure levels in vivo. ...	2011	21644570
pharmacokinetics, pharmacodynamics and allometric scaling of chloroquine in a murine malaria model.	chloroquine (cq) is an important antimalarial drug for the treatment of special patient groups and as a comparator for pre-clinical testing of new drugs. pharmacokinetic data for cq in animal models are limited, hence we conducted a three-part investigation, comprising: (i) pharmacodynamic studies of cq and cq plus dihydroartemisinin (dha) in plasmodium berghei infected mice; (ii) pharmacokinetic studies of cq in healthy and malaria-infected mice; and (iii) interspecies allometric scaling for cq ...	2011	21646487
exogenous nitric oxide decreases brain vascular inflammation, leakage and venular resistance during plasmodium berghei anka infection in mice.	abstract: background: cerebral malaria (cm) is a lethal complication of plasmodium falciparum infections. in the plasmodium berghei anka (pba) murine model, cm is associated with marked brain inflammation, increased expression of endothelial cell adhesion molecules and leukocyte and platelet accumulation in brain vessels, causing vascular occlusion and decreased blood flow, damaging the endothelium and leading to blood-brain barrier breakdown, leakage and hemorrhages. exogenous nitric oxide (no) ...	2011	21649904
alternative splicing of the anopheles gambiae dscam gene in diverse plasmodium falciparum infections.	in insects, including anopheles mosquitoes, dscam (down syndrome cell adhesion molecule) appears to be involved in phagocytosis of pathogens, and shows pathogen-specific splice-form expression between divergent pathogen (or parasite) types (e.g. between bacteria and plasmodium or between plasmodium berghei and plasmodium falciparum). here, data are presented from the first study of dscam expression in response to genetic diversity within a parasite species.	2011	21651790
genetic and transcriptional analysis of phosphoinositide-specific phospholipase c in plasmodium.	phosphoinositide-specific phospholipase c (pi-plc) is a major regulator of calcium-dependent signal transduction, which has been shown to be important in various processes of the malaria parasite plasmodium. pi-plc is generally implicated in calcium liberation from intracellular stores through the action of its product, inositol-(1,4,5)-trisphosphate, and is itself dependent on calcium for its activation. here we describe the plc genes from plasmodium species. the encoded proteins contain all do ...	2011	21651909
superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites.	while subunit vaccines have shown partial efficacy in clinical trials, radiation-attenuated sporozoites (ras) remain the "gold standard" for sterilizing protection against plasmodium infection in human vaccinees. the variability in immunogenicity and replication introduced by the extensive, random dna damage necessary to generate ras could be overcome by genetically attenuated parasites (gap) designed via gene deletion to arrest at defined points during liver-stage development. here, we demonstr ...	2011	21669394
the puf-family rna-binding protein puf2 controls sporozoite conversion to liver stages in the malaria parasite.	malaria is a vector-borne infectious disease caused by unicellular, obligate intracellular parasites of the genus plasmodium. during host switch the malaria parasite employs specialized latent stages that colonize the new host environment. previous work has established that gametocytes, sexually differentiated stages that are taken up by the mosquito vector, control expression of genes required for mosquito colonization by translational repression. sexual parasite development is controlled by a ...	2011	21673790
type i interferons suppress cd4(+) t-cell-dependent parasite control during blood-stage plasmodium infection.	during blood-stage plasmodium infection, large-scale invasion of rbcs often occurs before the generation of cellular immune responses. in plasmodium berghei anka (pba)-infected c57bl/6 mice, cd4(+) t cells controlled parasite numbers poorly, instead providing early help to pathogenic cd8(+) t cells. expression analysis revealed that the transcriptional signature of cd4(+) t cells from pba-infected mice was dominated by type i ifn (ifn-i) and ifn-╬│-signalling pathway-related genes. a role for if ...	2011	21674481
glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones--a new strategy to combat malarial parasites.	our work on targeting redox equilibria of malarial parasites propagating in red blood cells has led to the selection of six 1,4-naphthoquinones, which are active at nanomolar concentrations against the human pathogen plasmodium falciparum in culture and against plasmodium berghei in infected mice. with respect to safety, the compounds do not trigger hemolysis or other signs of toxicity in mice. concerning the antimalarial mode of action, we propose that the lead benzyl naphthoquinones are initia ...	2011	21682307
characterization of a new phosphatase from plasmodium.	plasmodium falciparum malaria is the most important parasitic disease worldwide, responsible for an estimated 1 million deaths annually. two p. falciparum genes code for putative phosphoglycerate mutases (pgmases), a widespread protein group characterized by the involvement of histidine residues in their catalytic mechanism. pgmases are responsible for the interconversion between 2 and 3-phosphoglycerate, an intermediate step in the glycolysis pathway. we have determined the crystal structures o ...	2011	21689687
apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in toxoplasma gondii.	apicomplexa are important pathogens that include the causative agents of malaria, toxoplasmosis, and cryptosporidiosis. apicomplexan parasites contain a relict chloroplast, the apicoplast. the apicoplast is indispensable and an attractive drug target. the apicoplast is home to a 1-deoxy-d-xylulose-5-phosphate (doxp) pathway for the synthesis of isoprenoid precursors. this pathway is believed to be the most conserved function of the apicoplast, and fosmidomycin, a specific inhibitor of the pathwa ...	2011	21690250
rodent blood-stage plasmodium survive in dendritic cells that infect naive mice.	plasmodium spp. parasites cause malaria in 300 to 500 million individuals each year. disease occurs during the blood-stage of the parasite's life cycle, where the parasite is thought to replicate exclusively within erythrocytes. infected individuals can also suffer relapses after several years, from plasmodium vivax and plasmodium ovale surviving in hepatocytes. plasmodium falciparum and plasmodium malariae can also persist after the original bout of infection has apparently cleared in the blood ...	2011	21690346
the ifn-+¦-inducible gtpase, irga6, protects mice against toxoplasma gondii but not against plasmodium berghei and some other intracellular pathogens.	clearance of infection with intracellular pathogens in mice involves interferon-regulated gtpases of the irg protein family. experiments with mice genetically deficient in members of this family such as irgm1(lrg-47), irgm3(igtp), and irgd(irg-47) has revealed a critical role in microbial clearance, especially for toxoplasma gondii. the in vivo role of another member of this family, irga6 (iigp, iigp1) has been studied in less detail. we investigated the susceptibility of two independently gener ...	2011	21698150
resistance of a rodent malaria parasite to a thymidylate synthase inhibitor induces an apoptotic parasite death and imposes a huge cost of fitness.	the greatest impediment to effective malaria control is drug resistance in plasmodium falciparum, and thus understanding how resistance impacts on the parasite's fitness and pathogenicity may aid in malaria control strategy.	2011	21698180
4-aminoquinoline analogues and its platinum (ii) complexes as antimalarial agents.	the high incidence of malaria and drug-resistant strains of plasmodium have turned this disease into a problem of major health importance. one of the approaches used to control it is to search for new antimalarial agents, such as quinoline derivates. this class of compounds composes a broad group of antimalarial agents, which are largely employed, and inhibits the formation of +¦-haematin (malaria pigment), which is lethal to the parasite. more specifically, 4-aminoquinoline derivates represent ...	2011	21704476
improvement of the observational method for plasmodium berghei oocysts in the midgut of mosquitoes.	there is a need for improving the method for counting oocysts of plasmodium berghei in the midgut of anopheles mosquitoes. the two methods currently used, the formalin fixation method and the mercurochrome staining method, have contradicting advantages and disadvantages. in the formalin fixation method, the specimen can be preserved but unstained oocysts were often indistinct from the insect tissue. while in the mercurochrome staining method, stained oocysts can be clearly distinguished from ins ...	2011	21707972
toxoplasma gondii peroxiredoxin promotes altered macrophage function, caspase-1-dependent il-1╬▓ secretion enhances parasite replication.	abstract: alternatively activated macrophages (aam) are a key feature th2 immunity and have been associated with a variety of roles during helminth infection. the role this cell subset plays in protzoan infection remain relatively unexplored, herein we describe the effects of a redox enzyme (rtgprx) derived from toxoplasma gondii on murine macrophage phenotype in vitro. rtgprx has been previously associated with the maintainence of parasite oxidative balance. here our experiments show that rtgpr ...	2011	21707997
caspase-1 activation of interleukin-1{beta} (il-1{beta}) and il-18 is dispensable for induction of experimental cerebral malaria.	malaria infection is initiated by sporozoite invasion of hepatocytes and asexual reproduction of liver stages, processes that are regarded to be "clinically and diagnostically silent." merozoites, which egress from hepatocytes, infect erythrocytes in periodic cycles and induce disease. how the host innate immune system contributes to disease outcomes and to the induction of effector cells during malaria remains unclear. likewise, how the initial liver stages may shape responses to blood-stage pa ...	2011	21708993
lessons from sickle cell disease in the treatment and control of malaria.		2011	21714653
cd8+ t effector memory cells protect against liver-stage malaria.	identification of correlates of protection for infectious diseases including malaria is a major challenge and has become one of the main obstacles in developing effective vaccines. we investigated protection against liver-stage malaria conferred by vaccination with adenoviral (ad) and modified vaccinia ankara (mva) vectors expressing pre-erythrocytic malaria ags. by classifying cd8(+) t cells into effector, effector memory (t(em)), and central memory subsets using cd62l and cd127 markers, we fou ...	2011	21715686
antagonistic antimalarial properties of pawpaw leaf aqueous extract in combination with artesunic acid in plasmodium berghei-infected mice.	artemisinins, the main stay in the treatment of malaria are used in combinations with other antimalarials to forestall resistance, as artemisinin-combination therapies (acts). however, acts are expensive and some of the non-artemisinin components are not well-tolerated by patients. there are several folkloric and scientific proofs of the efficacy of herbal remedies for malaria. mature leaves of carica papaya is widely used to treat malaria in several african countries. an act involving a medicin ...	2011	21715732
plasmodium berghei nk65 induces cerebral leukocyte recruitment in vivo: an intravital microscopic study.	malaria is second only to tuberculosis as the leading cause of morbidity and mortality as a consequence of a single infectious agent. much of the pathology of malaria arises from the inappropriate or excessive immune response mounted by the host in an attempt to eliminate the parasite. we here report the inflammatory changes observed in the cerebral microvasculature of c57bl/6 and balb/c mice that had been inoculated with plasmodium berghei nk65, a lethal strain of rodent malaria. although no ne ...	2011	21722620
Cellular and humoral immune effector mechanisms required for sterile protection against sporozoite challenge induced with the novel malaria vaccine candidate CelTOS.	The malarial protein CelTOS, for cell-traversal protein for ookinetes and sporozoites, from Plasmodium berghei has been shown to mediate malarial invasion of both vertebrate and insect host cells and is required for establishing their successful infections. In the vertebrate host, Plasmodium sporozoites traverse via a complex passage through cellular barriers in the skin and the liver sinusoid to infect hepatocytes. Induction of immunity targeted to molecules involved in sporozoite motility and ...	2011	21722682
synthesis and antimalarial activity of new heterocyclic hybrids based on chloroquine and thiazolidinone scaffolds.	a series of new 21 chloroquine heterocyclic hybrids containing either benzylamino fragment or n-(aminoalkyl)thiazolidin-4-one moiety were synthesized and screened for their antimalarial activity against chloroquine (cq)-sensitive 3d7 and multidrug-resistance dd2 strains of plasmodium falciparum. although no compounds more active than cq against 3d7 was found; against dd2 strain, six compounds, four of them with benzylamino fragment, showed an excellent activity, up to 3-fold more active than cq. ...	2011	21723734
vital functions of the malarial ookinete protein, ctrp, reside in the a domains.	the transformation of malaria ookinetes into oocysts occurs in the mosquito midgut and is a major bottleneck for parasite transmission. the secreted ookinete surface protein, circumsporozoite- and thrombospondin-related adhesive protein (trap)-related protein (ctrp), is essential for this transition and hence constitutes a potential target for malaria transmission blockade. ctrp is a modular multidomain protein containing six tandem von willebrand factor a-like (a) domains and seven tandem throm ...	2011	21729699
investigations on the role of a lysozyme from the malaria vector anopheles dirus during malaria parasite development.	a cdna encoding a lysozyme was obtained by rapid amplification of cdna ends-polymerase chain reaction (race-pcr) from females of the malaria vector anopheles dirus a (diptera: culicidae). the 623bp lysozyme (adlys c-1) cdna encodes the 120 amino acid mature protein with a predicted molecular mass of 13.4kda and theoretical pi of 8.45. six cysteine residues and a potential calcium binding motif that are present in adlys c-1 are highly conserved relative to those of c-type lysozymes found in other ...	2011	21741400
in the eye of experimental cerebral malaria.	cerebral malaria is the most severe complication of plasmodium falciparum infection, accounting for 1 million deaths per year. we characterized the murine disease using in vivo magnetic resonance imaging (mri) at 4.7 t, proving that ischemic edema is responsible for fatality. the aim of the present study was to identify early markers of experimental cerebral malaria using very high field conventional mri (11.75 t). cba/j mice infected with plasmodium berghei anka were observed at an early stage ...	2011	21741941
potential of a khaya ivorensis -alstonia boonei extract combination as antimalarial prophylactic remedy.	the decoction of the combined stem barks of khaya ivorensis a. chev. (meliaceae) and alstonia boonei de wild (apocynaceae) has a history of use in traditional medicine of central cameroon for malaria treatment but also for the prevention of the disease.	2011	21742022
structural basis for the regulation of cysteine-protease activity by a new class of protease inhibitors in plasmodium.	plasmodium cysteine proteases are essential for host-cell invasion and egress, hemoglobin degradation, and intracellular development of the parasite. the temporal, site-specific regulation of cysteine-protease activity is a prerequisite for survival and propagation of plasmodium. recently, a new family of inhibitors of cysteine proteases (icps) with homologs in at least eight plasmodium species has been identified. here, we report the 2.6-á+à x-ray crystal structure of the c-terminal, inhibitory ...	2011	21742259
the novel putative transporter npt1 plays a critical role in early stages of plasmodium berghei sexual development.	transmission of plasmodium species from a mammalian host to the mosquito vector requires the uptake, during an infected blood meal, of gametocytes, the precursor cells of the gametes. relatively little is known about the molecular mechanisms involved in the developmental switch from asexual development to sexual differentiation or the maturation and survival of gametocytes. here, we show that a gene coding for a novel putative transporter, npt1, plays a crucial role in the development of plasmod ...	2011	21752110
andrographolide: a novel antimalarial diterpene lactone compound from andrographis paniculata and its interaction with curcumin and artesunate.	andrographolide (and), the diterpene lactone compound, was purified by hplc from the methanolic fraction of the plant andrographis paniculata. the compound was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages of plasmodium falciparum in vitro and plasmodium berghei anka in vivo. ic(50)s for artesunate (as), andrographolide (and), and curcumin (cur) were found to be 0.05, 9.1 and 17.4?µm, respecti ...	2011	21760808
n-acetylglucosaminyltransferase v-deficiency increases susceptibility to murine malaria.	it is considered that several glycoproteins on erythrocytes in mammalian species are involved in malaria parasite infection. to elucidate the role of n-glycans on malaria parasite infection, we induced experimental murine malaria infection (using plasmodium berghei anka) in mice deficient in n-acetylglucosaminyltransferase v (mgat5), which is one of the enzymes involved in ß1,6-glcnac n-glycan biosynthesis. after infection, mgat5(-/-) mice showed severe body weight loss and parasitemia compared ...	2011	21767537
bioinformatics analysis and prediction for structure and function of nitric oxide synthase and similar proteins from plasmodium berghei.	to search and analyze nitric oxide synthase (nos) and similar proteins from plasmodium berghei(pb).	2011	21771405
antimalarial and analgesic activities of ethanolic leaf extract of panicum maximum.	to evaluate antiplasmodial and analgesic activities of ethanolic leaf extract/fractions of panicum maximum.	2011	21771695
arrested oocyst maturation in plasmodium parasites lacking type ii nadh:ubiquinone dehydrogenase.	the plasmodium mitochondrial electron transport chain (mtetc) has received considerable attention as a potential target for new antimalarial drugs. atovaquone, a potent inhibitor of plasmodium cytochrome bc1, in combination with proguanil is recommended for chemoprophylaxis and treatment of malaria. the type ii nadh:ubiquinone oxidoreductase (ndh2) is considered an attractive drug target, since its inhibition is thought to lead to the arrest of the mtetc and, as a consequence, pyrimidine biosynt ...	2011	21771793
the effect of helminth co-infection on malaria in mice: a meta-analysis.	the question of how helminths affect the course of concurrent malaria infection has attracted much interest in recent years. in particular, it has been suggested that by creating an anti-inflammatory immune environment, helminth co-infection may dampen both protective and immunopathological responses to malaria parasites, thus altering malaria infection dynamics and disease severity. both synergistic and antagonistic interactions are reported in the literature, and the causes of variation among ...	2011	21777589
the generation and evaluation of recombinant human iga specific for plasmodium falciparum merozoite surface protein 1-19 (pfmsp119).	abstract: background: human immunoglobulin g (igg) plays an important role in mediating protective immune responses to malaria. although human serum immunoglobulin a (iga) is the second most abundant class of antibody in the circulation, its contribution, if any, to protective responses against malaria is not clear. results: to explore the mechanism(s) by which iga may mediate a protective effect, we generated fully human iga specific for the c-terminal 19-kda region of plasmodium falciparum mer ...	2011	21781305
the effect of 2,2'-substitution on the metabolism and toxicity of dapsone in vitro and in vivo.	the effect of 2,2'-substitution with fluorine, methyl or trifluoromethyl groups on the toxicity, metabolism and pharmacological activity of dapsone has been investigated in vitro and in vivo. there was marked inter-species variation in the bioactivation (n-hydroxylation) of the compounds, as determined by methemoglobin formation. however, the inclusion of fluorine significantly (p<0.01) reduced methemoglobin formation compared with dapsone in all species studied. all three analogs resulted in si ...	1998	21781861
deltamethrin exposure affects host resistance to plasmodium infection in mice.	effects of exposure to deltamethrin on host resistance to malaria infection (plasmodium berghei) were examined in swiss albino male mice. four doses of deltamethrin were initially tested with two non-lethal doses, 5 and 10mg/kg, selected for more detailed study. survival times of infected mice did not change when they were exposed to the compound for 14 days before the infection. however, survival times were shortened when they were exposed to the compound, particularly at the high-dose, after a ...	2005	21783571
comparative efficacy of pre-erythrocytic whole organism vaccine strategies against the malaria parasite.	despite major efforts over the past 50 years to develop a malaria vaccine, no product has been licensed yet. irradiated sporozoites are the benchmark for an experimental live-attenuated malaria vaccine that induces potent protection against re-infection in humans and animal models. lasting protection can also be elicited by parasite attenuation via tailored genetic modification or drug cover leading to renewed interest in whole-organism vaccination strategies. in this study, we systematically co ...	2011	21787828
critical role for a stage-specific actin in male exflagellation of the malaria parasite.	male gametogenesis occurs directly after uptake of malaria parasites by the mosquito vector and leads to the release of eight nucleated flagellar gametes. here, we report that one of the two parasite actin isoforms, named actin ii, is essential for this process. disruption of actin ii in plasmodium berghei resulted in viable asexual blood stages, but male gametogenesis was specifically inhibited. upon activation, male gametocyte dna was replicated normally and axonemes assembled, but egress from ...	2011	21790945
global proteomic analysis of plasma from mice infected with plasmodium berghei anka using two dimensional gel electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry.	abstract: background: a global proteomic strategy was used to identify proteins, which are differentially expressed in the murine model of severe malaria in the hope of facilitating future development of novel diagnostic, disease monitoring and treatment strategies. methods: mice (4-week-old cd1 male mice) were infected with plasmodium berghei anka strain, and infection allowed to establish until a parasitaemia of 30% was attained. total plasma and albumin depleted plasma samples from infected a ...	2011	21791037
organelle segregation into plasmodium liver stage merozoites.	the liver stage of the plasmodium parasite remains one of the most promising targets for intervention against malaria as it is clinically silent, precedes the symptomatic blood stage and represents a bottleneck in the parasite life cycle. however, many aspects of the development of the parasite during this stage are far from understood. during the liver stage, the parasite undergoes extensive replication, forming tens of thousands of infectious merozoites from each invading sporozoite. this impl ...	2011	21801293
prevention of experimental cerebral malaria by flt3 ligand during infection with plasmodium berghei anka.	dendritic cells are the most potent antigen-presenting cells, but their roles in blood-stage malaria-infection are not fully understood. we examined the effects of flt3 ligand, a cytokine which induces dendritic cell production, in vivo on the course of infection with plasmodium berghei anka. mice treated with flt3 ligand showed preferential expansion of cd8(+) dendritic cells and granulocytes, lower parasitemia, and were protected from the development of lethal experimental cerebral malaria (ec ...	2011	21807908
design and evaluation of primaquine-artemisinin hybrids as a multistage anti-malarial strategy.	it is widely accepted that the struggle against malaria depends on the development of new strategies to fight infection. the "magic bullet" thought to be necessary to reach eradication should not only provide treatment for all plasmodium sp. that infect human red blood cells but also eliminate the replicative and dormant liver forms of the parasite. moreover, these goals should ideally be achieved by using different mechanisms of action to avoid the development of resistance. to that end, two hy ...	2011	21807973
Conserved peptide sequences bind to actin and enolase on the surface of Plasmodium berghei ookinetes.	SUMMARYThe description of Plasmodium ookinete surface proteins and their participation in the complex process of mosquito midgut invasion is still incomplete. In this study, using phage display, a consensus peptide sequence (PWWP) was identified in phages that bound to the Plasmodium berghei ookinete surface and, in selected phages, bound to actin and enolase in overlay assays with ookinete protein extracts. Actin was localized on the surface of fresh live ookinetes by immunofluorescence and ele ...	2011	21816124
interaction between ciprofloxacin and chloroquine in mice infected with chloroquine resistant plasmodium berghei : interaction between ciprofloxacin and chloroqune.	the increasing spread of chloroquine resistant malaria has intensified the search for new antimalarial treatment, especially drugs that can be used in combination. ciprofloxacin (cfx) a fluoroquinolone commonly used to treat bacterial infections has been shown to possess significant antimalarial activity both in vitro and in vivo. thus efforts in this study were devoted to evaluating the antimalarial activity of combination of chloroquine (cq) with varying doses (10, 20, 40 80, 160-ámg/kg body w ...	2011	21826489
infection intensity dependent responses of anopheles gambiae to african malaria parasites plasmodium falciparum.	malaria remains a devastating disease despite efforts for control and prevention. extensive studies using mostly rodent infection models reveal that successful plasmodium parasite transmission by the african mosquito vector anopheles gambiae depends on finely tuned vector/parasite interactions. here we investigate the transcriptional response of a. gambiae to geographically related plasmodium falciparum populations at varying infection intensities and different infection stages. these responses ...	2011	21844236
antiplasmodial activity of xanthium strumarium against plasmodium berghei-infected balb/c mice.	the present work was undertaken to evaluate the antiplasmodial activity of ethanolic leaves extract of traditional medicinal plant xanthium strumarium in plasmodium berghei-infected balb/c mice along with phytochemical screening and acute toxicity test to support its traditional medicinal use as a malaria remedy. the ethanolic leaves extract of x. strumarium (elexs) 150, 250, 350 and 500 mg/kg/day demonstrated dose-dependent chemosuppression during early and established infection long with signi ...	2011	21847597
antimalarial activities of new guanidylimidazole and guanidylimidazoline derivatives.	a series of new guanidylimidazole derivatives was prepared and evaluated in mice and rhesus monkeys infected with malarial sporozoites. the majority of the new compounds showed poor metabolic stability and weak in vitro activities in three clones of plasmodium falciparum. compounds 8a, 8h, 9a, 16a, and 16e cured the mice infected with sporozoites of p. berghei at 160 and 320 mg/kg/day × 3 po. compounds 8a showed better causal prophylactic activity than primaquine, tafenoquine, and malarone in ...	2011	21848332
inactivation of a plasmodium apicoplast protein attenuates formation of liver merozoites.	malaria parasites undergo a population expansion inside the host liver before disease onset. developmental arrest inside host hepatocytes elicits protective immune responses. therefore, elucidation of the molecular mechanisms leading to mature hepatic merozoites, which initiate the pathogenic blood phase, also informs anti-malaria vaccine strategies. using targeted gene deletion in the rodent model malaria parasite plasmodium berghei, we show that a plasmodium-specific apicoplast protein plays a ...	2011	21848587
structure-activity relationships of 4-position diamine quinoline methanols as intermittent preventative treatment (ipt) against plasmodium falciparum.	a library of diamine quinoline methanols were designed based on the mefloquine scaffold. the systematic variation of the 4-position amino alcohol side chain led to analogues that maintained potency while reducing accumulation in the central nervous system (cns). although the mechanism of action remains elusive, these data indicate that the 4-position side chain is critical for activity and that potency (as measured by ic(90)) does not correlate with accumulation in the cns. a new lead compound, ...	2011	21854078
cns hypoxia is more pronounced in murine cerebral than noncerebral malaria and is reversed by erythropoietin.	cerebral malaria (cm) is associated with high mortality and risk of sequelae, and development of adjunct therapies is hampered by limited knowledge of its pathogenesis. to assess the role of cerebral hypoxia, we used two experimental models of cm, plasmodium berghei anka in cba and c57bl/6 mice, and two models of malaria without neurologic signs, p. berghei k173 in cba mice and p. berghei anka in balb/c mice. hypoxia was demonstrated in brain sections using intravenous pimonidazole and staining ...	2011	21854739
reverse fosmidomycin derivatives against the antimalarial drug target ispc (dxr).	reverse hydroxamate-based inhibitors of ispc, a key enzyme of the non-mevalonate pathway of isoprenoid biosynthesis and a validated antimalarial target, were synthesized and biologically evaluated. the binding mode of one derivative in complex with ecispc and a divalent metal ion was clarified by x-ray analysis. pilot experiments have demonstrated in vivo potential.	2011	21866890
Development and evaluation of a prototype non-woven fabric filter for purification of malaria-infected blood.	Many malaria-related studies depend on infected red blood cells (iRBCs) as fundamental material; however, infected blood samples from human or animal models include leukocytes (white blood cells or WBCs), especially difficult to separate from iRBCs in cases involving Plasmodium vivax. These host WBCs are a source of contamination in biology, immunology and molecular biology studies, requiring their removal. Non-woven fabric (NWF) has the ability to adsorb leukocytes and is already used as filtra ...	2011	21867550
Quinoline antimalarials containing a dibemethin group are active against chloroquinone-resistant Plasmodium falciparum and inhibit chloroquine transport via the P. falciparum chloroquine-resistance transporter (PfCRT).	A series of 4-amino-7-chloroquinolines with dibenzylmethylamine (dibemethin) side chains were shown to inhibit synthetic hemozoin formation. These compounds were equally active against cultures of chloroquine-sensitive (D10) and chloroquine-resistant (K1) Plasmodium falciparum. The most active compound had an IC(50) value comparable to that of chloroquine, and its potency was undiminished when tested in three additional chloroquine-resistant strains. The three most active compounds exhibited lit ...	2011	21875063
heterogeneous and tissue-specific regulation of effector t cell responses by ifn-gamma during plasmodium berghei anka infection.	ifn-γ and t cells are both required for the development of experimental cerebral malaria during plasmodium berghei anka infection. surprisingly, however, the role of ifn-γ in shaping the effector cd4(+) and cd8(+) t cell response during this infection has not been examined in detail. to address this, we have compared the effector t cell responses in wild-type and ifn-γ(-/-) mice during p. berghei anka infection. the expansion of splenic cd4(+) and cd8(+) t cells during p. berghei anka infection ...	2011	21880980
FLP/FRT-mediated conditional mutagenesis in pre-erythrocytic stages of Plasmodium berghei.	We describe here a highly efficient procedure for conditional mutagenesis in Plasmodium. The procedure uses the site-specific recombination FLP-FRT system of yeast and targets the pre-erythrocytic stages of the rodent Plasmodium parasite P. berghei, including the sporozoite stage and the subsequent liver stage. The technique consists of replacing the gene under study by an FRTed copy (i.e., flanked by FRT sites) in the erythrocytic stages of a parasite clone that expresses the flip (FLP) recombi ...	2011	21886105
comparison of the reactivity of antimalarial 1,2,4,5-tetraoxanes with 1,2,4-trioxolanes in the presence of ferrous iron salts, heme, and ferrous iron salts/phosphatidylcholine.	dispiro-1,2,4,5-tetraoxanes and 1,2,4-trioxolanes represent attractive classes of synthetic antimalarial peroxides due to their structural simplicity, good stability, and impressive antimalarial activity. we investigated the reactivity of a series of potent amide functionalized tetraoxanes with fe(ii)gluconate, feso(4), feso(4)/tempo, feso(4)/phosphatidylcholine, and heme to gain knowledge of their potential mechanism of bioactivation and to compare the results with the corresponding 1,2,4-triox ...	2011	21888440
experimentally controlled downregulation of the histone chaperone fact in plasmodium berghei reveals that it is critical to male gamete fertility.	human fact (facilitates chromatin transcription) consists of the proteins spt16 and ssrp1 and acts as a histone chaperone in the (dis)assembly of nucleosome (and thereby chromatin) structure during transcription and dna replication. we identified a plasmodium berghei protein, termed fact-l, with homology to the spt16 subunit of fact. epitope tagging of fact-l showed nuclear localization with high expression in the nuclei of (activated) male gametocytes. the gene encoding fact-l could not be dele ...	2011	21899698