| functional characterization of an lccl-lectin domain containing protein family in plasmodium berghei. | using bioinformatic, proteomic, immunofluorescence, and genetic cross methods, we have functionally characterized a family of putative parasite ligands as potential mediators of cell-cell interactions. we name these proteins the limulus clotting factor c, coch-5b2, and lgl1 (lccl)-lectin adhesive-like protein (lap) family. we demonstrate that this family is conserved amongst plasmodium spp. it possesses a unique arrangement of adhesive protein domains normally associated with extracellular prote ... | 2004 | 15562607 |
| genetically modified plasmodium parasites as a protective experimental malaria vaccine. | malaria is a mosquito-borne disease that is transmitted by inoculation of the plasmodium parasite sporozoite stage. sporozoites invade hepatocytes, transform into liver stages, and subsequent liver-stage development ultimately results in release of pathogenic merozoites. liver stages of the parasite are a prime target for malaria vaccines because they can be completely eliminated by sterilizing immune responses, thereby preventing malarial infection. using expression profiling, we previously ide ... | 2004 | 15580261 |
| design, synthesis and evaluation of 5-substituted amino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines as novel antimalarials. | novel 5-substituted amino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines were designed based on a pharmacophore developed for potent antimalarial activity using chem-x and moe softwares. the designed molecules were synthesized by following a novel route and were evaluated by rane's test for blood schizonticidal activity in mice infected by plasmodium berghei. based on the mean survival time (mst) data, of the nine compounds evaluated, three had curative potential when compared with chloroquine. | 2005 | 15582413 |
| a proteomic analysis of malaria biology: integration of old literature and new technologies. | the genomic revolution has brought a new vitality into research on plasmodium, its insect and vertebrate hosts. at the cellular level nowhere is the impact greater than in the analysis of protein expression and the 'assembly' of the supramolecular machines that together comprise the functional cell. the repetitive phases of invasion and replication that typify the malaria life cycle, together with the unique phase of sexual differentiation provide a powerful platform on which to investigate the ... | 2004 | 15582521 |
| the role of programmed cell death in plasmodium-mosquito interactions. | many host-parasite interactions are regulated in part by the programmed cell death of host cells or the parasite. here we review evidence suggesting that programmed cell death occurs during the early stages of the development of the malaria parasite in its vector. zygotes and ookinetes of plasmodium berghei have been shown to die by programmed cell death (apoptosis) in the midgut lumen of the vector anopheles stephensi, or whilst developing in vitro. several morphological markers, indicative of ... | 2004 | 15582523 |
| curcumin for malaria therapy. | malaria remains a major global health concern. new, inexpensive, and effective antimalarial agents are urgently needed. here we show that curcumin, a polyphenolic organic molecule derived from turmeric, inhibits chloroquine-resistant plasmodium falciparum growth in culture in a dose dependent manner with an ic(50) of approximately 5 microm. additionally, oral administration of curcumin to mice infected with malaria parasite (plasmodium berghei) reduces blood parasitemia by 80-90% and enhances th ... | 2005 | 15582601 |
| a surface phospholipase is involved in the migration of plasmodium sporozoites through cells. | plasmodium sporozoites, injected by mosquitoes into the skin of the host, traverse cells during their migration to hepatocytes where they continue their life cycle. the mechanisms used by the parasite to rupture the plasma membrane of the host cells are not known. here we report the presence of a phospholipase on the surface of plasmodium berghei sporozoites (p. berghei phospholipase; pb pl) and demonstrate that it is involved in the establishment of a malaria infection in vivo. pb pl is highly ... | 2004 | 15590623 |
| [construction of the subtracted cdna libraries related to artemisinin-resistance of plasmodium berghei]. | to construct the subtracted cdna libraries related to artemisinin-resistance of plasmodium berghei using suppression subtractive hybridization pcr (ssh pcr). | 2004 | 15597707 |
| [additive therapeutic effect of a combination of artemether and daphnetin against plasmodium berghei in mice]. | to investigate the therapeutic effect of a combination of artemether and daphnetin against plasmodium berghei anka strain in mice. | 2004 | 15597713 |
| gene expression in plasmodium berghei ookinetes and early oocysts in a co-culture system with mosquito cells. | using an in vitro development system for plasmodium berghei sporogonic stages and microarray technology we examined parasite gene expression during ookinete invasion of aedes cells and the ensuing oocyst development. a number of genes were found to be differentially expressed. the most prominent class of up-regulated elements corresponded to products involved in protein synthesis and metabolism. furthermore, several previously studied genes with a known in vivo developmental profile matched publ ... | 2005 | 15610814 |
| abca1 gene deletion protects against cerebral malaria: potential pathogenic role of microparticles in neuropathology. | the atp-binding cassette transporter a1 (abca1) modulates the transbilayer distribution of phosphatidylserine at the outer leaflet of the plasma membrane. this external exposure of phosphatidylserine is a hallmark of microparticle production and is impaired in abca1(-/-) mice. in this study, we report about the complete resistance to cerebral malaria of these mice. on analysis of histological and systemic parameters we evidenced an impairment of cellular responses to plasmodium berghei anka infe ... | 2005 | 15632021 |
| a comprehensive survey of the plasmodium life cycle by genomic, transcriptomic, and proteomic analyses. | plasmodium berghei and plasmodium chabaudi are widely used model malaria species. comparison of their genomes, integrated with proteomic and microarray data, with the genomes of plasmodium falciparum and plasmodium yoelii revealed a conserved core of 4500 plasmodium genes in the central regions of the 14 chromosomes and highlighted genes evolving rapidly because of stage-specific selective pressures. four strategies for gene expression are apparent during the parasites' life cycle: (i) housekeep ... | 2005 | 15637271 |
| medicine: knockout malaria vaccine? | | 2005 | 15650722 |
| overexpression and altered nucleocytoplasmic distribution of anopheles ovalbumin-like srpn10 serpins in plasmodium-infected midgut cells. | the design of effective, vector-based malaria transmission blocking strategies relies on a thorough understanding of the molecular and cellular interactions that occur during the parasite sporogonic cycle in the mosquito. during plasmodium berghei invasion, transcription from the srpn10 locus, encoding four serine protease inhibitors of the ovalbumin family, is strongly induced in the mosquito midgut. herein we demonstrate that intense induction as well as redistribution of srpn10 occurs specifi ... | 2005 | 15659062 |
| a plasmodium sporozoite protein with a membrane attack complex domain is required for breaching the liver sinusoidal cell layer prior to hepatocyte infection. | plasmodium sporozoites are injected into the mammalian host during mosquito blood feeding and carried by the blood stream to the liver, where they infect hepatocytes and develop into erythrocyte-invasive forms. to reach the hepatocytes, sporozoites must cross the liver sinusoidal cell layer, which separates the hepatocytes from the circulatory system. little is known about the molecular mechanisms by which sporozoites breach this cellular barrier. here we report that a protein with a membrane at ... | 2005 | 15659064 |
| [cerebral malaria, a key role for endothelial cells?]. | five to six hundred millions of people, throughout the world, suffer from malaria and more than one million die each year as a consequence, in about 20% of the cases, of cerebral malaria, an important complication of plasmodium falciparum infection (holding & snow, 2001). despite many studies, the physiopathology of these cerebral occurrences is not understood, especially concerning the intricacy and respective roles of the various mechanisms identified: sequestration of parasitized red cells in ... | 2004 | 15662934 |
| invariant valpha14 chain nkt cells promote plasmodium berghei circumsporozoite protein-specific gamma interferon- and tumor necrosis factor alpha-producing cd8+ t cells in the liver after poxvirus vaccination of mice. | understanding the protective mechanism in the liver induced by recombinant vaccines against the pre-erythrocytic stages of malaria is important for vaccine development. most studies in mice have focused on splenic and peripheral blood t cells and identified gamma interferon (ifn-gamma)-producing cd8+ t cells as correlates of protection, which can be induced by prime-boost vaccination with recombinant poxviruses. invariant natural killer t (valpha14inkt) cells can also protect against liver stage ... | 2005 | 15664925 |
| the chemotherapy of rodent malaria. lxii. drug combinations to impede the selection of drug resistance, part 5: rates of development of resistance to some inhibitors of folate metabolism and to artesunate. | in recent years infection with chloroquine-resistant plasmodium falciparum has been combatted with two long-acting antimalarials, pyrimethamine and sulfadoxine, in the combination known as fansidar that exerts a strong, synergistic action on the asexual stages of the parasite. this second-line regimen, however, is failing increasingly because of the selection of resistant clones in endemic areas, and effective, safe, alternative drugs or drug combinations that are also affordable are urgently ne ... | 2004 | 15667710 |
| in vivo antimalarial activity of essential oils from cymbopogon citratus and ocimum gratissimum on mice infected with plasmodium berghei. | the essential oils obtained by hydrodistillation from fresh leaves of cymbopogon citratus and ocimum gratissimum growing in cameroon were analyzed by gc and gc/ms. the main constituents of the oil of ocimum gratissimum were gamma-terpinene (21.9 %), beta-phellandrene (21.1 %), limonene (11.4 %) and thymol (11.2 %), while the oil of cymbopogon citratus contained geranial (32.8 %), neral (29.0 %), myrcene (16.2 %) and beta-pinene (10.5 %). the effects of these oils on the growth of plasmodium berg ... | 2005 | 15678368 |
| parasitology. malaria vaccines: back to the future? | | 2005 | 15681372 |
| imidazolidin-4-one derivatives of primaquine as novel transmission-blocking antimalarials. | imidazolidin-4-one derivatives of primaquine were synthesized as potential double prodrugs of the parent drug. the title compounds inhibit the development of the sporogonic cycle of plasmodium berghei, affecting the appearance of oocysts in the midguts of the mosquitoes. the imidazolidin-4-ones are very stable, both in human plasma and in ph 7.4 buffer, indicating that they are active per se. thus, imidazolidin-4-ones derived from 8-aminoquinolines represent a new entry in antimalarial structure ... | 2005 | 15689174 |
| the anopheles gambiae gamma1 laminin directly binds the plasmodium berghei circumsporozoite- and trap-related protein (ctrp). | | 2005 | 15694493 |
| plasmodium liver stage developmental arrest by depletion of a protein at the parasite-host interface. | plasmodium parasites of mammals, including the species that cause malaria in humans, infect the liver first and develop there into clinically silent liver stages. liver stages grow and ultimately produce thousands of first-generation merozoites, which initiate the erythrocytic cycles causing malaria pathology. here, we present a plasmodium protein with a critical function for complete liver stage development. uis4 (up-regulated in infective sporozoites gene 4) is expressed exclusively in infecti ... | 2005 | 15699336 |
| differences in the neurochemical characteristics of the cortex and striatum of mice with cerebral malaria. | fatal murine cerebral malaria is an encephalitis and not simply a local manifestation in the brain of a systemic process. histopathologically, murine cerebral malaria has been characterized by monocyte adherence to the endothelium of the microvasculature, activation of microglial cells, swelling of endothelial cell nuclei, microvasculature damage, and breakdown of the blood-brain barrier with cerebral oedema. brain parenchymal cells have been proposed to be actively involved in the pathogenesis ... | 2005 | 15700754 |
| c3d binding to the circumsporozoite protein carboxy-terminus deviates immunity against malaria. | the immunogenicity of recombinant protein or anti-viral dna vaccines can be significantly improved by the addition of tandem copies of the complement fragment c3d. we sought to determine if the efficacy of a circumsporozoite protein (csp)-based dna vaccine delivered to mouse skin by gene gun was improved by using this strategy. instead, we found that c3d suppressed the protective immunity against plasmodium berghei malaria infection and deviated immunity, most notably by suppressing the inductio ... | 2005 | 15710912 |
| design, synthesis and antimalarial activity of trifluoromethylartemisinin-mefloquine dual molecules. | | 2005 | 15723441 |
| functional and biochemical modifications in skeletal muscles from malarial mice. | although it is well established that patients suffering from malaria experience skeletal muscle problems (contracture, aches, fatigue, weakness), detailed studies have not been performed to investigate changes in the contractile function and biochemical properties of intact and skinned skeletal muscles of mammals infected with malaria. to this end, we investigated such features in the extensor digitorium longus (edl, fast-twitch, glyocolytic) and in the soleus (sol, slow-twitch, oxidative) muscl ... | 2005 | 15728139 |
| antimalarial activities and therapeutic properties of febrifugine analogs. | febrifugine is the active principal isolated 50 years ago from the chinese herb chang shan (dichroa febrifuga lour), which has been used as an antimalarial in chinese traditional medicine for more than 2,000 years. however, intensive study of the properties of febrifugine has been hindered for decades due to its side effects. we report new findings on the effects of febrifugine analogs compared with those of febrifugine extracted from the dry roots of d. febrifuga. the properties of the extracte ... | 2005 | 15728920 |
| do malaria ookinete surface proteins p25 and p28 mediate parasite entry into mosquito midgut epithelial cells? | p25 and p28 are related ookinete surface proteins highly conserved throughout the plasmodium genus that are under consideration as candidates for inclusion in transmission-blocking vaccines. previous research using transgenic rodent malaria parasites lacking p25 and p28 has demonstrated that these proteins have multiple partially redundant functions during parasite infection of the mosquito vector, including an undefined role in ookinete traversal of the mosquito midgut epithelium, and it has be ... | 2005 | 15733320 |
| comparative study on schizontocidal activity of recrystallized or crude daphnetin against malaria parasites. | to compare the schizontocidal activity of recrystallized or crude daphnetin against malaria parasites in vivo. | 2004 | 15745243 |
| midgut epithelial responses of different mosquito-plasmodium combinations: the actin cone zipper repair mechanism in aedes aegypti. | in vivo responses of midgut epithelial cells to ookinete invasion of three different vector-parasite combinations, aedes aegypti-plasmodium gallinaceum, anopheles stephensi-plasmodium berghei, and a. stephensi-p. gallinaceum, were directly compared by using enzymatic markers and immunofluorescence stainings. our studies indicate that, in a. aegypti and a. stephensi ookinetes traverse the midgut via an intracellular route and inflict irreversible damage to the invaded cells. these two mosquito sp ... | 2005 | 15753303 |
| genome update: base skews in 200+ bacterial chromosomes. | | 2005 | 15758208 |
| hgf/met signalling protects plasmodium-infected host cells from apoptosis. | plasmodium, the causative agent of malaria, migrates through several hepatocytes before initiating a malaria infection. we have previously shown that this process induces the secretion of hepatocyte growth factor (hgf) by traversed cells, which renders neighbour hepatocytes susceptible to infection. the signalling initiated by hgf through its receptor met has multifunctional effects on various cell types. our results reveal a major role for apoptosis protection of host cells by hgf/met signallin ... | 2005 | 15760460 |
| chemosensitizing action of cepharanthine against drug-resistant human malaria, plasmodium falciparum. | we have established a system of in vitro and in vivo assays to prioritize plant extracts that can serve as a source of drug candidates for the treatment of malaria, an infectious disease that affects nearly 40% of the world's population. in the present study, we have investigated the biological potential of one such plant-derived drug lead, cepharanthine. in vitro growth inhibition studies indicated this compound possessed good antiplasmodial activity without mediating a cytotoxic response. base ... | 2005 | 15763374 |
| a strong cd8+ t cell response is elicited using the synthetic polypeptide from the c-terminus of the circumsporozoite protein of plasmodium berghei together with the adjuvant qs-21: quantitative and phenotypic comparison with the vaccine model of irradiated sporozoites. | stable protective immunity can be achieved against malaria by the injection of radiation-attenuated sporozoites (gamma-spz) and is mediated by ifn-gamma producing cd8+ t cells targeting the pre-erythrocytic stages. an efficient malaria vaccine should mimic this immunity. we compared the immune response specific for the circumsporozoite protein (csp) of plasmodium berghei (p. berghei), an important target of this protective response, elicited in mice immunized with the long synthetic polypeptide ... | 2005 | 15780728 |
| the natural killer complex regulates severe malarial pathogenesis and influences acquired immune responses to plasmodium berghei anka. | the natural killer complex (nkc) is a genetic region of highly linked genes encoding several receptors involved in the control of nk cell function. the nkc is highly polymorphic, and allelic variability of various nkc loci has been demonstrated in inbred mice. making use of balb.b6-cmv1r congenic mice, in which the nkc from disease-susceptible c57bl/6 mice has been introduced into the disease-resistant balb/c background, we show here that during murine malaria infection, the nkc regulates a rang ... | 2005 | 15784573 |
| synthesis of some cryptolepine analogues, assessment of their antimalarial and cytotoxic activities, and consideration of their antimalarial mode of action. | a series of analogues of cryptolepine (1) have been synthesized and evaluated for their in vitro antiplasmodial and cytotoxic properties. the ic(50) values of several compounds (11a, 11k-m, 11o, 13) against plasmodium falciparum (strain k1) were <0.1 mum, 5-10-fold lower than that of 1 but their cytotoxicities were only 2-4 times greater than that of 1. compounds with a halogen in the quinoline ring and a halogen or a nitro group in the indole ring have enhanced antiplasmodial activity. in mice ... | 2005 | 15801861 |
| convenient access both to highly antimalaria-active 10-arylaminoartemisinins, and to 10-alkyl ethers including artemether, arteether, and artelinate. | an economical phase-transfer method is used to prepare 10-arylaminoartemisinins from dha and arylamines, and artemether, arteether, and artelinate from the corresponding alcohols. in vivo sc screens against plasmodium berghei and p. yoelii in mice reveal that the p-fluorophenylamino derivative 5 g is some 13 and 70 times, respectively, more active than artesunate; this reflects the very high sc activity of 10-alkylaminoartemisinins. however, through the po route, the compounds are less active th ... | 2005 | 15812783 |
| thalidomide influences the function of macrophages and increases the survival of plasmodium berghei-infected cba mice. | malaria remains a major cause of morbidity and mortality in vast areas of the world, mainly due to the severe forms of plasmodium falciparum infection. the exacerbated immune response, with increased production of tnf and reactive nitrogen and oxygen intermediates, plays a role in the complex pathogenesis of the disease. it is recognised that thalidomide decreases tnf production and may modulate several functions of the immune system. this work evaluated the influence of thalidomide on macrophag ... | 2005 | 15817259 |
| arrest in the liver--a genetically defined malaria vaccine? | | 2005 | 15829544 |
| apoptotic plasmodium-infected hepatocytes provide antigens to liver dendritic cells. | malaria starts with infection of the host liver by plasmodium sporozoites. inoculation with radiation-attenuated plasmodium sporozoites induces complete protection against malaria. protection is mediated by dendritic cells (dcs) and cd8(+) t cells, but the source of parasite antigens mediating this response remains unclear. here, we show that hepatocytes infected with irradiated plasmodium sporozoites undergo apoptosis shortly after infection. infection with irradiated sporozoites induces the re ... | 2005 | 15838783 |
| motility and infectivity of plasmodium berghei sporozoites expressing avian plasmodium gallinaceum circumsporozoite protein. | avian and rodent malaria sporozoites selectively invade different vertebrate cell types, namely macrophages and hepatocytes, and develop in distantly related vector species. to investigate the role of the circumsporozoite (cs) protein in determining parasite survival in different vector species and vertebrate host cell types, we replaced the endogenous cs protein gene of the rodent malaria parasite plasmodium berghei with that of the avian parasite p. gallinaceum and control rodent parasite p. y ... | 2005 | 15839899 |
| the in vitro and in vivo antimalarial activity of cardiospermum halicacabum l. and momordica foetida schumch. et thonn. | two plants cardiospermum halicacabum l. and momordica foetida schumch. et thonn traditionally used to treat symptoms of malaria in parts of east and central africa were screened for in vitro and in vivo antimalarial activity. using the nitro tetrazolium blue-based parasite lactate dehydrogenase assay as used by [makler, m.t., ries, j.m., williams, j.a., bancroft, j.e., piper, r.c., gibbins, b.l., hinrichs, d.j., 1993. parasite lactate dehydrogenase as an assay for plasmodium falciparum drug sens ... | 2005 | 15848033 |
| [automatic analysis of micronuclei by flow cytometry using anti-cd71-fitc and pi staining]. | to explore flow cytometry (fcm) based method for automatic analysis of micronuclei (mn) in cells staining with anti-cd71-fitc and pi. | 2005 | 15862014 |
| a mitogen-activated protein kinase regulates male gametogenesis and transmission of the malaria parasite plasmodium berghei. | differentiation of malaria parasites into sexual forms (gametocytes) in the vertebrate host and their subsequent development into gametes in the mosquito vector are crucial steps in the completion of the parasite's life cycle and transmission of the disease. the molecular mechanisms that regulate the sexual cycle are poorly understood. although several signal transduction pathways have been implicated, a clear understanding of the pathways involved has yet to emerge. here, we show that a plasmod ... | 2005 | 15864297 |
| direct processing and presentation of antigen from malaria sporozoites by professional antigen-presenting cells in the induction of cd8 t-cell responses. | irradiated malaria sporozoites induce better protection than viable untreated sporozoites. we observed early differences between irradiated and viable untreated sporozoites in priming responses in vivo to a protective cd8 t-cell epitope, pb9, of the circumsporozoite protein of plasmodium berghei. sporozoites were processed for mhc class i presentation by dendritic cells (dc) to prime pb9-specific ifn-gamma-producing cd8 t cells. dc pulsed with untreated and irradiated sporozoites were similarly ... | 2005 | 15877610 |
| synthesis and antimalarial activity of e-2-quinolinylbenzocycloalcanones. | a series of e-2-quinolinylbenzocycloalcanones 5-21 were prepared and evaluated for their activity to inhibit beta-hematin formation and the hydrolysis of hemoglobin in vitro. positive compounds for both assays were also tested for their efficacy in rodent plasmodium berghei. compounds 6, 16, 19, and 20, were the most promising. inhibition of beta-hematin formation was minimal when a hydrogen or methoxy groups were present on the position 8 of the quinoline and position 4' of the indanone ring as ... | 2005 | 15878218 |
| brain macrophage activation in murine cerebral malaria precedes accumulation of leukocytes and cd8+ t cell proliferation. | although the activation of brain macrophages is associated with both human and mouse cerebral malaria (cm) the relative contributions of the heterogeneous populations of brain macrophages to the disease are unknown. in this work, we dissociate for the first time inflammatory monocytes from resident brain macrophages in mice developing cm when infected with plasmodium berghei. based on the differential expression of cd45 in brain macrophage cell populations and by using bone-marrow (bm) chimeras ... | 2005 | 15885309 |
| synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives. | phenylurenyl chalcone derivatives have been synthesized and tested as inhibitors of in vitro development of a chloroquine-resistant strain of plasmodium falciparum, activity of the cysteine protease falcipain-2, in vitro globin hydrolysis, beta-hematin formation, and murine plasmodium berghei malaria. the most active antimalarial compound was 1-[3'-n-(n'-phenylurenyl)phenyl]-3(3,4,5-trimethoxyphenyl)-2-propen-1-one 49, with an ic(50) of 1.76 microm for inhibition of p. falciparum development. re ... | 2005 | 15887974 |
| ookinete-induced midgut peroxidases detonate the time bomb in anopheline mosquitoes. | previous analysis of the temporal-spatial relationship between ookinete migration and the cellular localization of genes mediating midgut immune defense responses suggested that, in order to survive, parasites must complete invasion before toxic chemicals ("a bomb") are generated by the invaded cell. recent studies indicate that ookinete invasion induces tyrosine nitration as a two-step reaction, in which nos induction is followed by a localized increase in peroxidase activity. peroxidases utili ... | 2005 | 15894189 |
| fas has a role in cerebral malaria, but not in proliferation or exclusion of the murine parasite in mice. | we examined the susceptibility of murine fas-deficient mutants to malaria infection in order to investigate the role of fas in an experimental murine model of cerebral malaria (cm). we infected mice of b6 and cba wild-type and mutant backgrounds with plasmodium berghei anka. the incidence of cm in the mutant mice (b6-lpr, cba-lprcg) was decreased by about 50% compared with wild-type control strains at 2 weeks after infection. we did not observe significant differences of parasitemia during a mur ... | 2005 | 15900502 |
| intravital observation of plasmodium berghei sporozoite infection of the liver. | plasmodium sporozoite invasion of liver cells has been an extremely elusive event to study. in the prevailing model, sporozoites enter the liver by passing through kupffer cells, but this model was based solely on incidental observations in fixed specimens and on biochemical and physiological data. to obtain direct information on the dynamics of sporozoite infection of the liver, we infected live mice with red or green fluorescent plasmodium berghei sporozoites and monitored their behavior using ... | 2005 | 15901208 |
| transcriptome analysis of anopheles stephensi-plasmodium berghei interactions. | simultaneous microarray-based transcription analysis of 4987 anopheles stephensi midgut and plasmodium berghei infection stage specific cdnas was done at seven successive time points: 6, 20 and 40h, and 4, 8, 14 and 20 days after ingestion of malaria infected blood. the study reveals the molecular components of several anopheles processes relating to blood digestion, midgut expansion and response to plasmodium-infected blood such as digestive enzymes, transporters, cytoskeletal and structural co ... | 2005 | 15907562 |
| protein farnesyltransferase inhibitors exhibit potent antimalarial activity. | new therapeutics to combat malaria are desperately needed. here we show that the enzyme protein farnesyltransferase (pft) from the malaria parasite plasmodium falciparum (p. falciparum) is an ideal drug target. pft inhibitors (pftis) are well tolerated in man, but are highly cytotoxic to p. falciparum. because of their anticancer properties, pftis comprise a highly developed class of compounds. pftis are ideal for the rapid development of antimalarials, allowing "piggy-backing" on previously gar ... | 2005 | 15916422 |
| reduced cerebral blood flow and n-acetyl aspartate in a murine model of cerebral malaria. | cerebral malaria is an important cause of morbidity and mortality in many parts of the world. it has been suggested that cerebral malaria is associated with reduced perfusion due to the blockage of blood vessels by parasitized erythrocytes; although, no quantitative validation of this has been done. we infected c57bl/6 mice with the anka strain of plasmodium berghei and on day 6 of infection we investigated alterations in brain function using arterial spin labeling mri and proton mrs. mr images ... | 2005 | 15918069 |
| cassane- and norcassane-type diterpenes from caesalpinia crista of indonesia and their antimalarial activity against the growth of plasmodium falciparum. | the ch2cl2 extract of the seed kernels of caesalpinia crista, which exhibited promising antimalarial activity against plasmodium berghei-infected mice in vivo, was examined and resulted in the isolation of seven new furanocassane-type diterpenes [caesalpinins c-g (1-5) and norcaesalpinins d and e (6, 7)] together with norcaesalpinins a-c (8-10) and 11 known compounds (norcaesalpinins a-c, 2-acetoxy-3-deacetoxycaesaldekarin e, caesalmin b, caesaldekarin e, caesalpin f, 14(17)-dehydrocaesalpin f, ... | 2005 | 15921414 |
| genetically modified plasmodium highlights the potential of whole parasite vaccine strategies. | a genetically modified malaria sporozoite might breathe new life into the traditional approach to vaccine development, that of using whole organisms. mueller and colleagues recently knocked out a gene, uis3, from the rodent parasite, plasmodium berghei, and demonstrated that the sporozoite forms could not develop beyond the stage of the life cycle in the liver (thus not giving rise to clinical disease, which is associated with blood infection) but could induce protection against subsequent chall ... | 2005 | 15922944 |
| driving midgut-specific expression and secretion of a foreign protein in transgenic mosquitoes with agaper1 regulatory elements. | the anopheles gambiae adult peritrophic matrix protein 1 (agaper1) regulatory elements were used to drive the expression of phospholipase a2 (pla2), a protein known to disrupt malaria parasite development in mosquitoes. these agaper1 regulatory elements were sufficient to promote the accumulation of pla2 in midgut epithelial cells before a blood meal and its release into the lumen upon blood ingestion. plasmodium berghei oocyst formation was reduced by approximately 80% (74-91% range) in transge ... | 2005 | 15926896 |
| synthesis and evaluation of beta-carbolinium cations as new antimalarial agents based on pi-delocalized lipophilic cation (dlc) hypothesis. | several beta-carbolines including naturally occurring substances and their corresponding cationic derivatives were synthesized and evaluated for antimalarial (antiplasmodial) activity in vitro and in vivo. a tetracyclic carbolinium salt was elucidated for antileishmanial and antitrypanosomal activities in vitro as well as antiplasmodial activity. quarternary carbolinium cations showed much higher potencies in vitro than electronically neutral beta-carbolines and a good correlation was observed b ... | 2005 | 15930777 |
| revealing the molecular determinants of gender in malaria parasites. | malaria parasites have a complex life cycle with asexual multiplication in a vertebrate host and obligate sexual reproduction in the mosquito; however, commitment to sexual development begins in the vertebrate with differentiation of female and male gametocytes. in this issue of cell, khan et al. (2005) used elegant approaches to purify male and female gametocytes and elucidated their respective proteome, providing the basis for understanding sexual development in this pathogen. | 2005 | 15935749 |
| proteome analysis of separated male and female gametocytes reveals novel sex-specific plasmodium biology. | gametocytes, the precursor cells of malaria-parasite gametes, circulate in the blood and are responsible for transmission from host to mosquito vector. the individual proteomes of male and female gametocytes were analyzed using mass spectrometry, following separation by flow sorting of transgenic parasites expressing green fluorescent protein, in a sex-specific manner. promoter tagging in transgenic parasites confirmed the designation of stage and sex specificity of the proteins. the male proteo ... | 2005 | 15935755 |
| supplementation of cxcl12 (cxcl12) induces homing of cd11c+ dendritic cells to the spleen and enhances control of plasmodium berghei malaria in balb/c mice. | in malaria, parasitaemia is controlled in the spleen, a multicomponent organ that undergoes changes in its cellular constituents to control the parasite. during this process, dendritic cells (dcs) orchestrate the positioning of effector cells in a timely manner for optimal parasite clearance. we have recently demonstrated that cxcl12 [stromal cell-derived factor-1 (cxcl12)] supplementation partially restores the ability to control parasitaemia in plasmodium berghei-infected mice. in the present ... | 2005 | 15946257 |
| plasmodium berghei ookinetes bind to anopheles gambiae and drosophila melanogaster annexins. | using a proteomic approach we identified polypeptides from anopheles gambiae and drosophila melanogaster protein extracts that selectively bind purified plasmodium berghei ookinetes in vitro; these were two and three distinct polypeptides, respectively, with an apparent molecular weight of about 36 kda. combining two-dimensional electrophoresis and maldi-tof (matrix-associated laser desorption ionization time of flight) mass spectrometry we determined that the polypeptides correspond to isomorph ... | 2005 | 15948958 |
| antimalarial activities and toxicities of three plants used as traditional remedies for malaria in the democratic republic of congo: croton mubango , nauclea pobeguinii and pyrenacantha staudtii. | the antimalarial activities of crude extracts and 17 fractions from the partition of 80%-methanolic extracts of three plants (the stem bark of croton mubango, the stem bark of nauclea pobeguinii and the leaves of pyrenacantha staudtii) used as antimalarial remedies in the democratic republic of congo were studied both in vitro (against plasmodium falciparum) and in mice infected with pl. berghei berghei. the toxic effects of dried aqueous extracts of the plants were also investigated, in uninfec ... | 2005 | 15949182 |
| dispiro-1,2,4-trioxane analogues of a prototype dispiro-1,2,4-trioxolane: mechanistic comparators for artemisinin in the context of reaction pathways with iron(ii). | single electron reduction of the 1,2,4-trioxane heterocycle of artemisinin (1) forms primary and secondary carbon-centered radicals. the complex structure of 1 does not lend itself to a satisfactory dissection of the electronic and steric effects that influence the formation and subsequent reaction of these carbon-centered free radicals. to help demarcate these effects, we characterized the reactions of achiral dispiro-1,2,4-trioxolane 4 and dispiro-1,2,4-trioxanes 5-7 with ferrous bromide and 4 ... | 2005 | 15960511 |
| plasmodium berghei nk65: studies on the effect of treatment duration and inoculum size on recrudescence. | recrudescence of plasmodium berghei nk65 infection was studied to examine factors affecting recrudescence. treatment with a high dose of chloroquine did not prevent recrudescence, but an extended duration of treatment suppressed the frequency of recrudescence. infection with a larger number of parasites also resulted in more frequent recrudescences. recrudescent parasites were as sensitive to chloroquine as those before treatment. splenectomized mice were administered carbon particles, infected, ... | 2005 | 15961077 |
| laminin and the malaria parasite's journey through the mosquito midgut. | during the invasion of the mosquito midgut epithelium, plasmodium ookinetes come to rest on the basal lamina, where they transform into the sporozoite-producing oocysts. laminin, one of the basal lamina's major components, has previously been shown to bind several surface proteins of plasmodium ookinetes. here, using the recently developed rnai technique in mosquitoes, we used a specific dsrna construct targeted against the lanb2 gene (laminin gamma1) of anopheles gambiae to reduce its mrna leve ... | 2005 | 15961736 |
| genetic control of parasite clearance leads to resistance to plasmodium berghei anka infection and confers immunity. | unprecedented cure after infection with the lethal plasmodium berghei anka was observed in an f2 progeny generated by intercrossing the wild-derived wla and the laboratory c57bl/6 mouse strains. resistant mice were able to clear parasitaemia and establish immunity. the observed resistance was disclosed as a combinatorial effect of genetic factors derived from the two parental strains. genetic mapping of survival time showed that the wla allele at a locus on chromosome 1 (colocalizing with berghe ... | 2005 | 15973462 |
| the complex interplay between mosquito positive and negative regulators of plasmodium development. | the malaria parasite, plasmodium, requires sexual development in the mosquito before it can be transmitted to the vertebrate host. mosquito genes are able to substantially modulate this process, which can result in major decreases in parasite numbers. even in susceptible mosquitoes, haemolymph proteins implicated in systemic immune reactions, together with local epithelial responses, cause lysis of more than 80% of the ookinetes that cross the mosquito midgut. in a refractory mosquito strain, im ... | 2005 | 15996894 |
| the immune status of kupffer cells profoundly influences their responses to infectious plasmodium berghei sporozoites. | multi-factorial immune mechanisms underlie protection induced with radiation-attenuated plasmodia sporozoites (gamma-spz). spz pass through kupffer cells (kc) before invading hepatocytes but the involvement of kc in protection is poorly understood. in this study we investigated whether gamma-spz-immune kc respond to infectious spz in a manner that is distinct from the response of naive kc to infectious spz. kc were isolated from (1) naive, (2) spz-infected, (3) gamma-spz-immune, and (4) gamma-sp ... | 2005 | 15997465 |
| the chemotherapy of rodent malaria. lxiii. drug combinations to impede the selection of drug resistance, part 6: the potential value of chlorproguanil and dapsone in combination, and with the addition of artesunate. | resistance is readily produced in rodent malaria using the single-dose, '2%-relapse technique' (2%rt) against the individual compounds chlorproguanil (cpg), chlorcycloguanil (ccg), cycloguanil, dapsone (dds) and artesunate (asn). using the '4-day test', a low level of synergism or a simple additional action between cpg and dds was observed with multiple dosing of these two compounds in a combination. resistance to a 1 : 3 combination of cpg-dds was selected in each of three parasite lines: plasm ... | 2005 | 16004705 |
| functional genomic analysis of midgut epithelial responses in anopheles during plasmodium invasion. | the malaria parasite plasmodium must complete a complex developmental life cycle within anopheles mosquitoes before it can be transmitted into the human host. one day after mosquito infection, motile ookinetes traverse the midgut epithelium and, after exiting to its basal site facing the hemolymph, develop into oocysts. previously, we have identified hemolymph factors that can antagonize or promote parasite development. | 2005 | 16005290 |
| differences in biochemical properties of the plasmodial falcipain-2 and berghepain-2 orthologues: implications for in vivo screens of inhibitors. | falcipain-2a, the cysteine protease of plasmodium falciparum has been proposed as a good drug target. this study evaluated the suitability of plasmodium berghei as the animal model and reports the first functional expression and characterization of the falcipain-2a orthologue, berghepain-2. comparative studies revealed that the orthologues exhibited different biochemical properties. berghepain-2 demonstrated optimal activity at a narrower ph optima of 5.5-6 and a lack of preference for substrate ... | 2005 | 16019160 |
| a malarial cysteine protease is necessary for plasmodium sporozoite egress from oocysts. | the plasmodium life cycle is a sequence of alternating invasive and replicative stages within the vertebrate and invertebrate hosts. how malarial parasites exit their host cells after completion of reproduction remains largely unsolved. inhibitor studies indicated a role of plasmodium cysteine proteases in merozoite release from host erythrocytes. to validate a vital function of malarial cysteine proteases in active parasite egress, we searched for target genes that can be analyzed functionally ... | 2005 | 16027235 |
| spiro and dispiro-1,2,4-trioxolanes as antimalarial peroxides: charting a workable structure-activity relationship using simple prototypes. | this paper describes the discovery of synthetic 1,2,4-trioxolane antimalarials and how we established a workable structure-activity relationship in the context of physicochemical, biopharmaceutical, and toxicological profiling. an achiral dispiro-1,2,4-trioxolane (3) in which the trioxolane is flanked by a spiroadamantane and spirocyclohexane was rapidly identified as a lead compound. nonperoxidic 1,3-dioxolane isosteres of 3 were inactive as were trioxolanes without the spiroadamantane. the tri ... | 2005 | 16033274 |
| how i became a biochemist. | | 2005 | 16036582 |
| the proteasome inhibitor mln-273 blocks exoerythrocytic and erythrocytic development of plasmodium parasites. | protein degradation is regulated during the cell cycle of all eukaryotic cells and is mediated by the ubiquitin-proteasome pathway. potent and specific peptide-derived inhibitors of the 20s proteasome have been developed recently as anti-cancer agents, based on their ability to induce apoptosis in rapidly dividing cells. here, we tested a novel small molecule dipeptidyl boronic acid proteasome inhibitor, named mln-273 on blood and liver stages of plasmodium species, both of which undergo active ... | 2005 | 16038394 |
| phagocyte-derived reactive oxygen species do not influence the progression of murine blood-stage malaria infections. | phagocyte-derived reactive oxygen species have been implicated in the clearance of malaria infections. we investigated the progression of five different strains of murine malaria in gp91(phox-/-) mice, which lack a functional nadph oxidase and thus the ability to produce phagocyte-derived reactive oxygen species. we found that the absence of functional nadph oxidase in the gene knockout mice had no effect on the parasitemia or total parasite burden in mice infected with either resolving (plasmod ... | 2005 | 16041008 |
| prolonged survival of a murine model of cerebral malaria by kynurenine pathway inhibition. | c57bl/6j mice infected with plasmodium berghei anka develop neurological dysfunction and die within 7 days of infection. we show that treatment of infected mice with a kynurenine-3-hydroxylase inhibitor prevents them from developing neurological symptoms and extends their life span threefold until severe anemia develops. | 2005 | 16041050 |
| [dna/mva combined immunization: antibody response to plasmodium falciparum merozoite surface protein 1 in mice]. | to explore the effect of dna/mva combined immunization in enhancing antibody response to msp1. | 2005 | 16042175 |
| systems biology in malaria research. | a recent publication of genome and expression analyses of the murine parasites plasmodium chabaudi chabaudi and plasmodium berghei presents the state of the art in plasmodium systems biology. by integrating genomics, transcriptomics and proteomics, the authors can classify and annotate genes by their expression profiles and can even detect evidence of posttranscriptional gene silencing in the murine malaria species. | 2005 | 16043412 |
| murine malaria parasite sequestration: cd36 is the major receptor, but cerebral pathology is unlinked to sequestration. | sequestration of malaria-parasite-infected erythrocytes in the microvasculature of organs is thought to be a significant cause of pathology. cerebral malaria (cm) is a major complication of plasmodium falciparum infections, and pfemp1-mediated sequestration of infected red blood cells has been considered to be the major feature leading to cm-related pathology. we report a system for the real-time in vivo imaging of sequestration using transgenic luciferase-expressing parasites of the rodent mala ... | 2005 | 16051702 |
| 4-aminoquinoline quinolizidinyl- and quinolizidinylalkyl-derivatives with antimalarial activity. | a set of quinolizidinyl and quinolizidinylalkyl derivatives of 4-amino-7-chloroquinoline and of 9-amino-6-chloro-2-methoxyacridine were prepared and tested in vitro against cq-sensitive (d-10) and cq-resistant (w-2) strains of plasmodium falciparum. all compounds but one exerted significant antimalarial activity. some of the quinolizidine derivatives were from 5 to 10 times more active than chloroquine on the cq-resistant strain. no toxicity against mammalian cells was observed. | 2005 | 16054368 |
| plants, symbiosis and parasites: a calcium signalling connection. | a unique family of protein kinases has evolved with regulatory domains containing sequences that are related to ca(2+)-binding ef-hands. in this family, the archetypal ca(2+)-dependent protein kinases (cdpks) have been found in plants and some protists, including the malarial parasite, plasmodium falciparum. recent genetic evidence has revealed isoform-specific functions for a cdpk that is essential for plasmodium berghei gametogenesis, and for a related chimeric ca(2+) and calmodulin-dependent ... | 2005 | 16072038 |
| immune signaling pathways regulating bacterial and malaria parasite infection of the mosquito anopheles gambiae. | we show that, in the malaria vector anopheles gambiae, expression of cecropin 1 is regulated by rel2, an nf-kappab-like transcription factor orthologous to drosophila relish. through alternative splicing, rel2 produces a full-length (rel2-f) and a shorter (rel2-s) protein isoform lacking the inhibitory ankyrin repeats and death domain. rna interference experiments show that, in contrast to drosophila relish, which responds solely to gram-negative bacteria, the anopheles rel2-f and rel2-s isoform ... | 2005 | 16076953 |
| a chemotactic response facilitates mosquito salivary gland infection by malaria sporozoites. | sporozoite invasion of mosquito salivary glands is critical for malaria transmission to vertebrate hosts. after release into the mosquito hemocoel, the means by which malaria sporozoites locate the salivary glands is unknown. we developed a matrigel-based in vitro system to observe and analyze the motility of gfp-expressing plasmodium berghei sporozoites in the presence of salivary gland products of anopheles stephensi mosquitoes using temperature-controlled, low-light-level video microscopy. sp ... | 2005 | 16081617 |
| imaging experimental cerebral malaria in vivo: significant role of ischemic brain edema. | the first in vivo magnetic resonance study of experimental cerebral malaria is presented. cerebral involvement is a lethal complication of malaria. to explore the brain of susceptible mice infected with plasmodium berghei anka, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). they reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. we provide the first in vivo demo ... | 2005 | 16093385 |
| malaria parasites in mosquitoes: laboratory models, evolutionary temptation and the real world. | a recent study describing the effect of plasmodium berghei infection on some anopheles gambiae immune genes demonstrates that p. berghei is responsible for the upregulation of several genes involved in the immune response that affect parasitic development differently during the ookinete-to-oocyst developmental transition. it is important to question the relevance of such results, which are based on a laboratory model system, when discussing host-parasite interactions and, especially, the develop ... | 2005 | 16099724 |
| effect of chloroquine on the expression of genes involved in the mosquito immune response to plasmodium infection. | chloroquine has been described to increase plasmodium infectivity to the mosquito vector and is known to affect the vertebrate host immune response including during malarial infection. although knowledge of the mosquito immune response has recently improved, nothing is known about the impact of chloroquine on mosquito immunity. in order to characterize the influence of chloroquine on the mosquito immune system, we have analyzed the effect of chloroquine on anopheles gambiae (i) serine proteases ... | 2005 | 16102418 |
| genetically attenuated, p36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells. | immunization with plasmodium sporozoites that have been attenuated by gamma-irradiation or specific genetic modification can induce protective immunity against subsequent malaria infection. the mechanism of protection is only known for radiation-attenuated sporozoites, involving cell-mediated and humoral immune responses invoked by infected hepatocytes cells that contain long-lived, partially developed parasites. here we analyzed sporozoites of plasmodium berghei that are deficient in p36p (p36p ... | 2005 | 16103357 |
| mapping antimalarial pharmacophores as a useful tool for the rapid discovery of drugs effective in vivo: design, construction, characterization, and pharmacology of metaquine. | resistant strains of plasmodium falciparum and the unavailability of useful antimalarial vaccines reinforce the need to develop new efficacious antimalarials. this study details a pharmacophore model that has been used to identify a potent, soluble, orally bioavailable antimalarial bisquinoline, metaquine (n,n'-bis(7-chloroquinolin-4-yl)benzene-1,3-diamine) (dihydrochloride), which is active against plasmodium berghei in vivo (oral id(50) of 25 micromol/kg) and multidrug-resistant plasmodium fal ... | 2005 | 16107142 |
| early cytokine production is associated with protection from murine cerebral malaria. | cerebral malaria (cm) is an infrequent but serious complication of plasmodium falciparum infection in humans. animal and human studies suggest that the pathogenesis of cm is immune mediated, but the precise mechanisms leading to cerebral pathology are unclear. in mice, infection with plasmodium berghei anka results in cm on day 6 postinoculation (p.i.), while infection with the closely related strain p. berghei k173 does not result in cm. infection with p. berghei k173 was associated with increa ... | 2005 | 16113282 |
| fetuin-a, a hepatocyte-specific protein that binds plasmodium berghei thrombospondin-related adhesive protein: a potential role in infectivity. | malaria infection is initiated when the insect vector injects plasmodium sporozoites into a susceptible vertebrate host. sporozoites rapidly leave the circulatory system to invade hepatocytes, where further development generates the parasite form that invades and multiplies within erythrocytes. previous experiments have shown that the thrombospondin-related adhesive protein (trap) plays an important role in sporozoite infectivity for hepatocytes. trap, a typical type-1 transmembrane protein, has ... | 2005 | 16113307 |
| anopheles gambiae srpn2 facilitates midgut invasion by the malaria parasite plasmodium berghei. | we report on a phylogenetic and functional analysis of genes encoding three mosquito serpins (srpn1, srpn2 and srpn3), which resemble known inhibitors of prophenoloxidase-activating enzymes in other insects. following rna interference induction by double-stranded rna injection, knockdown of srpn2 in adult anopheles gambiae produced a notable phenotype: the appearance of melanotic pseudotumours, which increased in size and number with time, indicating spontaneous melanization and association with ... | 2005 | 16113656 |
| plasmodium berghei alpha-tubulin ii: a role in both male gamete formation and asexual blood stages. | plasmodium falciparum contains two genes encoding different isotypes of alpha-tubulin, alpha-tubulin i and alpha-tubulin ii. alpha-tubulin ii is highly expressed in male gametocytes and forms part of the microtubules of the axoneme of male gametes. here we present the characterization of plasmodium berghei alpha-tubulin i and alpha-tubulin ii that encode proteins of 453 and 450 amino acids, respectively. alpha-tubulin ii lacks the well-conserved three amino acid c-terminal extension including a ... | 2005 | 16115694 |
| close association of invading plasmodium berghei and beta integrin in the anopheles gambiae midgut. | we have used confocal microscopy and an antibody against anopheles gambiae beta integrin to study this protein's distribution in the mosquito midgut and its relationship to invading plasmodium berghei parasites. an extensive reorganization of integrin is seen to take place in the midgut epithelial cells following the uptake of either non-infected or parasite-infected blood meal, probably reflecting the reshaping of the gut due to the presence of the food bolus and the peritrophic membrane that s ... | 2005 | 16116619 |
| bypassing the midgut results in development of plasmodium berghei oocysts in a refractory strain of anopheles gambiae (diptera: culicidae). | the l35 strain of anopheles gambiae giles was genetically selected for its ability to melanize and kill malaria parasites. a wide range of plasmodium species are subject to this response when orally ingested, including the rodent malaria, p. berghei. however, when we directly injected p. berghei into the hemocoel, we found that parasites developed normally to the oocyst stage. this work suggests that the parasite melanization response depends on the interaction of the ookinetes and the midgut. t ... | 2005 | 16119566 |
| toxicokinetics and hydrolysis of artelinate and artesunate in malaria-infected rats. | comparative toxicokinetic (tk) and hydrolysis studies of intravenously administered two new antimalarial agents, artelinate (al) and artesunate (as), were performed in malaria-infected rats using three daily equimolar doses (96 micromoles/kg). the tk evaluation was related to select one drug for severe malaria treatment in u.s. army. drug concentration of as with daily dose of 36.7 mg/kg was one-third less on day 3 than on day 1, which resembled its active metabolite, dihydroartemisinin (dha), s ... | 2005 | 16126618 |
| risk assessment and therapeutic indices of artesunate and artelinate in plasmodium berghei-infected and uninfected rats. | artesunate (as) is being developed as a potential agent for the treatment of severe and complicated malaria. a risk assessment of the therapeutic index and related hematological changes of as and artelinate (al) following daily intravenous injection for 3 days was conducted in plasmodium berghei-infected and uninfected rats. the minimum doses of as and al for parasitemia suppression were 2.3 and 2.5 mg/kg, respectively, and the suppressive doses for half parasitemia (sd50) were 7.4 and 8.6 mg/kg ... | 2005 | 16126619 |
| a malaria parasite-encoded vacuolar h(+)-atpase is targeted to the host erythrocyte. | the asexual development of malaria parasites inside the erythrocyte is accompanied by changes in the composition, structure, and function of the host cell membrane and cytoplasm. the parasite exports a membrane network into the host cytoplasm and several proteins that are inserted into the erythrocyte membrane, although none of these proteins has been shown to have enzymatic activity. we report here that a functional malaria parasite-encoded vacuolar (v)-h(+)-atpase is exported to the erythrocyt ... | 2005 | 16135514 |