Publications

antimalarial activity of allicin, a biologically active compound from garlic cloves.	the incidence of malaria is increasing, and there is an urgent need to identify new drug targets for both prophylaxis and chemotherapy. potential new drug targets include plasmodium proteases that play critical roles in the parasite life cycle. we have previously shown that the major surface protein of plasmodium sporozoites, the circumsporozoite protein (csp), is proteolytically processed by a parasite-derived cysteine protease, and this processing event is temporally associated with sporozoite ...	2006	16641443
new potential antimalarial agents: therapeutic-index evaluation of pyrroloquinazolinediamine and its prodrugs in a rat model of severe malaria.	tetra-acetamide pyrroloquinazolinediamine (pqd-a4) and bis-ethylcarbamyl pyrroloquinazolinediamine (pqd-be) are new derivatives of pyrroloquinazolinediamine (pqd) and are being investigated as potential chemotherapeutic agents for the treatment of malaria. comparative studies to assess the therapeutic indices of pqd-a4, pqd-be, and pqd were conducted in plasmodium berghei-infected rats following daily intragastric dosing for three consecutive days. artesunate (as), a standard drug for treatment ...	2006	16641431
antiplasmodial activity of cylicodiscus gabunensis.	the antimalarial activity of ethanolic stembark extract of cylicodiscus gabunensis was studied in vivo in mice infected with plasmodium berghei berghei during early and established infections as well as for repository activity. the ld(50) of the extract was determined to be 223.6 mg/kg, while doses of 250 mg/kg and above were found to be lethal to mice. cylicodiscus gabunensis extract (20-60 mg/kg/day) exhibited a significant (p<0.05) blood schizontocidal activity in 4-day early infection, repos ...	2006	16635557
neuronal apoptosis, metallothionein expression and proinflammatory responses during cerebral malaria in mice.	cerebral malaria (cm) is an acute encephalopathy in humans due to the infection with plasmodium falciparum. neuro-cognitive impairment following cm occurs in about 10% of the treated survivors, while the precise pathophysiological mechanism remains unknown. metallothionein i + ii (mt-i + ii) are increased during cns pathology and disorders. as previously shown, mt-i + ii are neuroprotective through anti-inflammatory, antioxidant and antiapoptotic functions. we have analyzed neuronal apoptosis an ...	2006	16624296
cerebral malaria: role of microparticles and platelets in alterations of the blood-brain barrier.	brain lesions of cerebral malaria (cm) are characterised by a sequestration of plasmodium falciparum-parasitised red blood cells (prbc), leucocytes and platelets within brain microvessels, by an excessive release of pro-inflammatory cytokines as well as by disruption of the blood-brain barrier (bbb). we evaluated the possibility that prbc and platelets interact and induce functional alterations in brain endothelium. using an in vitro model of endothelial lesion, we showed that platelets can act ...	2006	16600245
pathogenic t cells in cerebral malaria.	malaria remains a major global health problem and cerebral malaria (cm) is one of the most serious complications of this disease. recent years have seen important advances in our understanding of the pathogenesis of cerebral malaria. parasite sequestration, a hallmark of this syndrome, is thought to be solely responsible for the pathological process. however, this phenomenon cannot explain all aspects of the pathogenesis of cm. the use of an animal model, plasmodium berghei anka in mice, has all ...	2006	16600241
2-cys peroxiredoxin tpx-1 is involved in gametocyte development in plasmodium berghei.	peroxiredoxins (prxs) constitute a ubiquitous family of antioxidant enzymes involved in diverse cellular functions including cell proliferation and differentiation. to investigate the physiologic role of typical 2-cys prx in malaria parasites (tpx-1), we disrupted this gene in the rodent malaria parasite plasmodium berghei (pbtpx-1). the gene-disrupted parasite (prx ko) developed normally in mouse erythrocytes and multiplied at a rate similar to that of the parent strain (wt) during the experime ...	2006	16597467
using green fluorescent malaria parasites to screen for permissive vector mosquitoes.	the plasmodium species that infect rodents, particularly plasmodium berghei and plasmodium yoelii, are useful to investigate host-parasite interactions. the mosquito species that act as vectors of human plasmodia in south east asia, africa and south america show different susceptibilities to infection by rodent plasmodium species. p. berghei and p. yoelii infect both anopheles gambiae and anopheles stephensi, which are found mainly in africa and asia, respectively. however, it was reported that ...	2006	16569221
immunization with a circumsporozoite epitope fused to bordetella pertussis adenylate cyclase in conjunction with cytotoxic t-lymphocyte-associated antigen 4 blockade confers protection against plasmodium berghei liver-stage malaria.	the adenylate cyclase toxoid (act) of bordetella pertussis is capable of delivering its n-terminal catalytic domain into the cytosol of cd11b-expressing professional antigen-presenting cells such as myeloid dendritic cells. this allows delivery of cd8+ t-cell epitopes to the major histocompatibility complex (mhc) class i presentation pathway. recombinant detoxified act containing an epitope of the plasmodium berghei circumsporozoite protein (csp), indeed, induced a specific cd8+ t-cell response ...	2006	16552058
infection with plasmodium berghei boosts antibody responses primed by a dna vaccine encoding gametocyte antigen pbs48/45.	an important consideration in the development of a malaria vaccine for individuals living in areas of endemicity is whether vaccine-elicited immune responses can be boosted by natural infection. to investigate this question, we used plasmodium berghei anka blood-stage parasites for the infection of mice that were previously immunized with a dna vaccine encoding the p. berghei sexual-stage antigen pbs48/45. intramuscular immunization in mice with one or two doses of dna-pbs48/45 or of empty dna v ...	2006	16552033
effective targeting of liposomes to liver and hepatocytes in vivo by incorporation of a plasmodium amino acid sequence.	several species of the protozoan plasmodium effectively target mammalian liver during the initial phase of host invasion. the purpose of this study was to demonstrate that a plasmodium targeting amino acid sequence can be engineered into therapeutic nanoparticle delivery systems.	2006	16550476
piperidones with activity against plasmodium falciparum.	the increasing resistance of the malaria parasites has enforced new strategies of finding new drug targets. we have isolated two genes involved in spermidine metabolism, encoding deoxyhypusine synthase (dhs) and eukaryotic initiation factor 5a (eif-5a) in the malaria parasites. eif-5a is activated by the formation of the unusual amino acid hypusine. this process occurs in two steps. dhs transfers an aminobutyl moiety from the triamine spermidine to a specific lysine residue in the eif-5a precurs ...	2006	16550432
mosquito midguts and malaria: cell biology, compartmentalization and immunology.	the malaria parasite plasmodium has an absolute requirement for both a vertebrate and a mosquito host in order to complete its life cycle, and its interactions with the latter provide the focus for this review. the mosquito midgut represents one of the most challenging environments for the survival and development of plasmodium, and is thus also one of the most attractive sites for novel targeted malaria control strategies. during their attempts to cross the midgut epithelium en route to the sal ...	2006	16542314
rhop-3 protein conservation among plasmodium species and induced protection against lethal p. yoelii and p. berghei challenge.	in the present study, rhop-3 polymorphism among plasmodium falciparum field and laboratory isolates and among rodent plasmodium species was investigated and identified. the rhop-3 gene was found in all plasmodium species so far tested. the overall structure of the rhop-3 protein was found conserved among p. falciparum, plasmodium yoelii, and plasmodium berghei. however, it was more conserved among rodent plasmodium species than between p. falciparum and plasmodium vivax. the most conserved regio ...	2006	16541261
a mosquito 2-cys peroxiredoxin protects against nitrosative and oxidative stresses associated with malaria parasite infection.	malaria parasite infection in anopheline mosquitoes induces nitrosative and oxidative stresses that limit parasite development, but also damage mosquito tissues in proximity to the response. based on these observations, we proposed that cellular defenses in the mosquito may be induced to minimize self-damage. specifically, we hypothesized that peroxiredoxins (prxs), enzymes known to detoxify reactive oxygen species (ros) and reactive nitrogen oxide species (rnos), protect mosquito cells. we iden ...	2006	16540402
plasmodium berghei (anka): infection induces cyp2a5 and 2e1 while depressing other cyp isoforms in the mouse liver.	it has been reported that malaria infection impairs hepatic drug clearance and causes a down-regulation of cyp-mediated monooxygenase activities in rodents and humans. in the present study, we investigated the effects of plasmodium berghei infection on the activity of liver monooxygenases in female dba/2 and c57bl/6 mice. in both mouse strains, p. berghei infection decreased activities mediated by cyp1a (erod: dba/2 65.3%, c57bl/6 44.7%) and 2b (brod: dba/2 64.3%, c57bl/6 49.8%) subfamily isofor ...	2006	16540109
development and application of a positive-negative selectable marker system for use in reverse genetics in plasmodium.	a limitation of transfection of malaria parasites is the availability of only a low number of positive selectable markers for selection of transformed mutants. this is exacerbated for the rodent parasite plasmodium berghei as selection of mutants is performed in vivo in laboratory rodents. we here report the development and application of a negative selection system based upon transgenic expression of a bifunctional protein (yfcu) combining yeast cytosine deaminase and uridyl phosphoribosyl tran ...	2006	16537837
[cytochrome p-450 and the response to antimalarial drugs].	to assess the relationship between the genetic and phenotypic factors linked to the cytochrome p-450 enzyme system and the response to the antimalarial drugs chloroquine, amodiaquine, mefloquine, and proguanil, as well as to determine how certain biological and social factors of the host influence the behavior of this enzymatic complex.	2006	16536934
diels-alder/thiol-olefin co-oxygenation approach to antimalarials incorporating the 2,3-dioxabicyclo[3.3.1]nonane pharmacophore.	a diels-alder/thiol-olefin co-oxygenation approach to the synthesis of novel bicyclic endoperoxides 17a-22b is reported. some of these endoperoxides (e.g., 17b, 19b, 22a and 22b) have potent nanomolar in vitro antimalarial activity equivalent to that of the synthetic antimalarial agent arteflene. iron(ii)-mediated degradation of sulfone-endoperoxide 19b and spin-trapping with tempo provide a spin-trapped adduct 25 indicative of the formation of a secondary carbon centered radical species 24. rea ...	2006	16527481
recombinant human erythropoietin prevents the death of mice during cerebral malaria.	cerebral involvement during malaria is a complication that leads to seizure, coma, and death. the effect of new neuroprotective therapies has not yet been investigated, although cerebral malaria shares some features with neurological stroke. erythropoietin (epo) is one of the more promising drugs in this area. we measured the effect of epo on the survival of mice infected with plasmodium berghei anka and demonstrated that inoculations of recombinant human epo at the beginning of the clinical man ...	2006	16518761
antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a vanuatu marine sponge xestospongia sp.	as part of our search for new antimalarial drugs, we have screened for inhibitors of pfnek-1, a protein kinase of plasmodium falciparum, in south pacific marine sponges. on the basis of a preliminary screening, the ethanolic crude extract of a new species of xestospongia collected in vanuatu was selected for its promising activity. a bioassay-guided fractionation led us to isolate xestoquinone which inhibits pfnek-1 with an ic(50) around 1 microm. among a small panel of plasmodial protein kinase ...	2006	16513357
plasmodium falciparum erythrocyte invasion: a conserved myosin associated complex.	host cell invasion by apicomplexan parasites is powered by an actin/myosin motor complex that has been most thoroughly described in toxoplasma gondii tachyzoites. in t. gondii, two inner membrane complex (imc) proteins, the peripheral protein tggap45 and the transmembrane protein tggap50, form a complex with the myosin, tgmyoa, and its light chain, tgmlc1. this complex, referred to as the glideosome, anchors the invasion motor to the imc. we have identified and characterized orthologues of tgmlc ...	2006	16513191
perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria.	cerebral malaria is a serious complication of plasmodium falciparum infection. we have investigated the role of perforin in the pathogenesis of cerebral malaria in a murine model (plasmodium berghei anka (pba) infection). c57bl/6 mice demonstrated the typical neuropathological symptoms of experimental cerebral malaria infection from day 5p.i. and became moribund on day 6p.i. this pathology was not seen in pba-infected, perforin-deficient (pfp-/-) mice. from days 5-6p.i. onwards there was a signi ...	2006	16500656
[recent advances in the study of artemisinin-related 1,2,4-trioxanes and ozonides (1,2,4-trioxolanes) as antimalarials].		2005	16496665
plasmodium berghei: development of an irreversible experimental malaria model in wistar rats.	a protocol to infect five-week-old wistar rats by plasmodium berghei which resulted in 100% mortality was developed in this work. in order to accomplish this goal, the effect of the administration of 10(7) and 10(8) parasitized erythrocytes by i.v. and i.p. route was investigated. the animals inoculated with 10(7) parasitized red blood cells by i.p. and i.v. routes showed 25 and 50% mortality, respectively. inoculation with 10(8) parasitized erythrocytes by both routes resulted in a 100% lethal ...	2006	16494867
immunopathological consequences of the loss of engulfment genes: the case of abca1.	programmed cell death plays a crucial role in the maintenance of cell homeostasis. an initial, effector phase leads to the generation of apoptotic corpses and is closely followed by a swift clearance by professional or amateur phagocytes. several aspects distinguish this latter process of engulfment of dying cells from the classical forms of phagocytosis. they concern all aspects of the process from the recognition of the prey to the final outcome, i.e. immunological silence. the engulfment of d ...	2005	16471259
total syntheses of hexacyclinol, 5-epi-hexacyclinol, and desoxohexacyclinol unveil an antimalarial prodrug motif.		2006	16470558
the effects of blood feeding and exogenous supply of tryptophan on the quantities of xanthurenic acid in the salivary glands of anopheles stephensi (diptera: culicidae).	xanthurenic acid (xa), produced as a byproduct during the biosynthesis of insect eye pigment (ommochromes), is a strong inducer of plasmodium gametogenesis at very low concentrations. in previous studies, it was shown that xa is present in anopheles stephensi (diptera: culicidae) mosquito salivary glands and that during blood feeding the mosquitoes ingested their own saliva into the midgut. considering these two facts together, it is therefore likely that xa is discharged with saliva during bloo ...	2006	16469295
celtos, a novel malarial protein that mediates transmission to mosquito and vertebrate hosts.	the malarial parasite has two hosts in its life cycle, a vertebrate and a mosquito. we report here that malarial invasion into these hosts is mediated by a protein, designated cell-traversal protein for ookinetes and sporozoites (celtos), which is localized to micronemes that are organelles for parasite invasive motility. targeted disruption of the celtos gene in plasmodium berghei reduced parasite infectivity in the mosquito host approximately 200-fold. the disruption also reduced the sporozoit ...	2006	16468982
kupffer cell function during the erythocytic stage of malaria.	previous studies using isolated perfused rat liver in vivo have suggested that during the erythrocytic phase of malaria infection, overall phagocytosis by kupffer cells is enhanced. the aim of the present study was to further investigate the individual phagocytic capacity and prostaglandin e(2) (pge(2)) secretion of isolated kupffer cells in vitro, and the immunohistochemical characteristics of kupffer cells in vivo.	2006	16460493
improved transfection and new selectable markers for the rodent malaria parasite plasmodium yoelii.	the rodent malaria plasmodium yoelii is a useful model to study protective immunity to pre-erythrocytic stages of infection, pathogenesis of erythrocytic stages, and vaccine development. however, the utility of the p. yoelii model system has not been fully realized because transfection and genetic manipulation methodologies for this rodent species are less developed than that of another rodent species plasmodium berghei. here we report improved transfection efficiency using the amaxa nucleofecto ...	2006	16458371
simultaneous increases in immune-competent cells and nitric oxide in the spleen during plasmodium berghei infection in mice.	nitric oxide and other reactive nitrogen intermediates (rni) are thought to be important mediators of both immunological and pathological responses of the vertebrate host to malaria infection. the role of rni has been studied most often by assay of stable rni metabolites (nitrites, nitrates) in blood. this study evaluated the nature of the rni response of mice to malaria by analyzing the subsets of immune-competent cells within the organ displaying increased rni in vivo.	2006	16440118
protective and pathogenic roles of cd8+ t cells during malaria infection.	cd8+ t cells play a key role in protection against pre-erythrocytic stages of malaria infection. many vaccine strategies are based on the idea of inducing a strong infection-blocking cd8+ t cell response. here, we summarize what is known about the development, specificity and protective effect of malaria-specific cd8+ t cells and report on recent developments in the field. although work in mouse models continues to make progress in our understanding of the basic biology of these cells, many ques ...	2006	16438672
a calcium-dependent protein kinase regulates plasmodium ookinete access to the midgut epithelial cell.	plasmodium parasites are fertilized in the mosquito midgut and develop into motile zygotes, called ookinetes, which invade the midgut epithelium. here we show that a calcium-dependent protein kinase, cdpk3, of the rodent malarial parasite (plasmodium berghei) is produced in the ookinete stage and has a critical role in parasite transmission to the mosquito vector. targeted disruption of the cdpk3 gene decreased ookinete ability to infect the mosquito midgut by nearly two orders of magnitude. ele ...	2006	16430692
synthesis and antimalarial activity of new 3-arylquinoxaline-2-carbonitrile derivatives.	new series of 3-arylquinoxaline-carbonitrile derivatives have been synthesized from various 5-substituted or 5,6-disubstituted benzofuroxanes and tested for their in vitro and in vivo activity against the erythrocytic development of plasmodium falciparum strain with different chloroquine-resistance status. quinoxaline 1,4-dioxide derivatives showed superior antimalarial activity in respect to reduced quinoxaline analogues. the best activity was observed with nonsubstituted quinoxaline 1,4-dioxid ...	2005	16430030
systemic activation of dendritic cells by toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity.	the mechanisms responsible for the immunosuppression associated with sepsis or some chronic blood infections remain poorly understood. here we show that infection with a malaria parasite (plasmodium berghei) or simple systemic exposure to bacterial or viral toll-like receptor ligands inhibited cross-priming. reduced cross-priming was a consequence of downregulation of cross-presentation by activated dendritic cells due to systemic activation that did not otherwise globally inhibit t cell prolife ...	2006	16415871
synthesis of 2-azabicyclo[3.2.2]nonanes from bicyclo[2.2.2]octan-2-ones and their activities against trypanosoma brucei rhodesiense and plasmodium falciparum k1.	new 2-azabicyclo[3.2.2]nonanes were prepared from antiprotozoal bicyclo[2.2.2]octan-2-ones to investigate the influence of the replacement of the rigid bicyclo-octane structure by the more flexible bicyclo-nonane system on the antiplasmodial and antitrypanosomal activity.	2005	16401404
antimalarial and antiplasmodial activities of norneolignans. syntheses and sar.	a systematic change of the substituents and side chain of the norneolignan hinokiresinol afforded a 10 fold improvement of the ic(50) value toward inhibition of the growth of plasmodium falciparum. the more potent compounds controlled the parasitemia in mice infected with plasmodium berghei.	2006	16392829
novel surface display system for proteins on non-genetically modified gram-positive bacteria.	a novel display system is described that allows highly efficient immobilization of heterologous proteins on bacterial surfaces in applications for which the use of genetically modified bacteria is less desirable. this system is based on nonliving and non-genetically modified gram-positive bacterial cells, designated gram-positive enhancer matrix (gem) particles, which are used as substrates to bind externally added heterologous proteins by means of a high-affinity binding domain. this binding do ...	2006	16391130
pbcrk-1, the plasmodium berghei orthologue of p. falciparum cdc-2 related kinase-1 (pfcrk-1), is essential for completion of the intraerythrocytic asexual cycle.	the molecular mechanisms underlying gametocytogenesis in malaria parasites are not understood. plasmodium falciparum cdc2-related kinase 1 (pfcrk-1), a gene that is expressed predominantly in gametocytes, bears homology to the pitslre subfamily of cyclin-dependent kinases and has been hypothesized to function as a negative regulator of the cell cycle. we attempted to knock-out pbcrk-1, the p. berghei orthologue of pfcrk-1, but were unable to recover p. berghei parasites with a disrupted pbcrk-1 ...	2006	16375894
gene-expression profiling discriminates between cerebral malaria (cm)-susceptible mice and cm-resistant mice.	the development of cerebral malaria (cm) in mice with plasmodium berghei anka infection is under genetic control. brain gene-expression patterns were investigated in well-defined genetically cm-resistant (cm-r; balb/c and dba/2) and cm-susceptible (cm-s; c57bl/6 and cba/j) mice by use of cdna microarrays. by combining transcriptional profiling with rigorous statistical methods and cluster analysis, we identified a set of 69 genes that perfectly discriminated between mouse strains and between cm- ...	2006	16362897
preservation of borrelia kansas and plasmodium berghei.	[this corrects the article on p. 224 in vol. 20.].	1971	16349897
characterization of plasmodium falciparum cgmp-dependent protein kinase (pfpkg): antiparasitic activity of a pkg inhibitor.	cyclic gmp-dependent protein kinase (pkg) has been biochemically and genetically validated in toxoplasma gondii as a primary target responsible for the antiparasitic activity of the trisubstituted pyrrole 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1h pyrrol-3-yl] pyridine (compound 1) [biftu t, feng d, ponpipom m, et al. synthesis and sar of 2,3-diarylpyrrole inhibitors of parasite cgmp-dependent protein kinase as novel anticoccidial agents. bioorg med chem lett 2005;15:3296-301; gurnett ...	2006	16325279
do apoptotic plasmodium-infected hepatocytes initiate protective immune responses?		2006	16323145
transgenic plasmodium berghei sporozoites expressing beta-galactosidase for quantification of sporozoite transmission.	malaria transmission occurs during a blood-meal of an infected anopheles mosquito. visualization and quantification of sporozoites along the journey from the mosquito midgut, where they develop, to the vertebrate liver, their final target organ, is important for understanding many aspects of sporozoite biology. here we describe the generation of plasmodium berghei parasites that express the reporter gene lacz as a stable transgene, under the control of the sporozoite-specific csp promoter. trans ...	2006	16316690
an atypical mitogen-activated protein kinase controls cytokinesis and flagellar motility during male gamete formation in a malaria parasite.	the transmission of malaria parasites to the mosquito depends critically on the rapid initiation of sexual reproduction in response to triggers from the mosquito midgut environment. we here identify an essential function for an atypical mitogen-activated protein kinase of the rodent malaria parasite plasmodium berghei, pbmap-2, in male sexual differentiation and parasite transmission to the mosquito. a deletion mutant no longer expressing the pbmap-2 protein develops as wild type throughout the ...	2005	16313614
antimalarial activities of new pyrrolo[3,2-f]quinazoline-1,3-diamine derivatives.	wr227825 is an antimalarial pyrroloquinazolinediamine derivative with a high potency but a low therapeutic index. a series of carbamate, carboxamide, succinimide, and alkylamine derivatives of wr227825 were prepared to search for compounds with an improved therapeutic index. the new acetamides and imide showed potent cell growth inhibition against four clones of plasmodium falciparum (d-6, rcs, w-2, and tm91c235), with a 50% inhibitory concentration of approximately 0.01 ng/ml, and were highly a ...	2005	16304154
cell- rather than antibody-mediated immunity leads to the development of profound thrombocytopenia during experimental plasmodium berghei malaria.	experimental malarial thrombocytopenia can reach life-threatening levels and is believed to be due to abs targeting platelets for destruction by the reticuloendothelial system. however, we report that abs account for at most 15% of platelet destruction as plasmodium berghei-infected b cell-deficient mice exhibited profound thrombocytopenia (83%) as did c57bl/6 controls (98%). further, no significant increase in abs bound to intact platelets was observed during infection. p. berghei infection can ...	2005	16301680
generation of gene targeting constructs for plasmodium berghei by a pcr-based method amenable to high throughput applications.		2006	16290088
towards systematic identification of plasmodium essential genes by transposon shuttle mutagenesis.	after the deciphering of the genome sequences of several plasmodium species, efforts must turn to elucidating gene function and identifying essential gene products. however, random approaches are lacking and gene targeting is inefficient in plasmodium. here, we established shuttle transposon mutagenesis in plasmodium berghei. we constructed a mini-tn5 derivative that can transpose into parasite genes cloned in escherichia coli, providing an efficient means of generating knockout fragments. a 10( ...	2005	16284199
purinoceptors are involved in the induction of an osmolyte permeability in malaria-infected and oxidized human erythrocytes.	in human erythrocytes, infection by the malaria parasite plasmodium falciparum or oxidative stress induces a new organic osmolyte and anion permeability. to examine a role for autocrine purinoceptor signaling during this induction process, erythrocytic purinoceptor expression, and atp release were determined. furthermore, using pharmacological and genetic approaches the dependence on purinoceptor signaling of osmolyte permeability and plasmodium development, both in vitro and in vivo, were asses ...	2006	16267125
an immune-responsive serpin, srpn6, mediates mosquito defense against malaria parasites.	we have functionally analyzed the orthologous srpn6 genes from anopheles stephensi and anopheles gambiae using phylogenetic, molecular, reverse genetic, and cell biological tools. the results strongly implicate srpn6 in the innate immune response against plasmodium. this gene belongs to a mosquito-specific gene cluster including three additional anopheles serpins. srpn6 expression is induced by escherichia coli and both rodent and human malaria parasites. the gene is specifically expressed in mi ...	2005	16260729
antimalarial activity of 4-(5-trifluoromethyl-1h-pyrazol-1-yl)-chloroquine analogues.	the antimalarial activity of chloroquine-pyrazole analogues, synthesized from the reaction of 1,1,1-trifluoro-4-methoxy-3-alken-2-ones with 4-hydrazino-7-chloroquinoline, has been evaluated in vitro against a chloroquine resistant plasmodium falciparum clone. parasite growth in the presence of the test drugs was measured by incorporation of [(3)h]hypoxanthine in comparison to controls with no drugs. all but one of the eight (4,5-dihydropyrazol-1-yl) chloroquine 2 derivatives tested showed a sign ...	2006	16257205
antimalarial drug synergism and antagonism: mechanistic and clinical significance.	interactions between antimicrobial agents provide clues as to their mechanisms of action and influence the combinations chosen for therapy of infectious diseases. in the treatment of malaria, combinations of drugs, in many cases acting synergistically, are increasingly important in view of the frequency of resistance to single agents. the study of antimalarial drug interactions is therefore of great significance to both treatment and research. it is therefore worrying that the analysis of drug-i ...	2005	16243458
high efficiency transfection of plasmodium berghei facilitates novel selection procedures.	the use of transfection in the study of the biology of malaria parasites has been limited due to poor transfection efficiencies (frequency of 10(-6) to 10(-9)) and a paucity of selection markers. here, a new method of transfection, using non-viral nucleofector technology, is described for the rodent parasite plasmodium berghei. the transfection efficiency obtained (episomal and targeted integration into the genome) is in the range of 10(-2) to 10(-3). such high transfection efficiency strongly r ...	2006	16242190
the liver stage of plasmodium berghei inhibits host cell apoptosis.	plasmodium berghei is the causative agent of rodent malaria and is widely used as a model system to study the liver stage of plasmodium parasites. the entry of p. berghei sporozoites into hepatocytes has extensively been studied, but little is known about parasite-host interaction during later developmental stages of the intracellular parasite. growth of the parasite far beyond the normal size of the host cell is an important stress factor for the infected cell. cell stress is known to trigger p ...	2005	16238623
activation of calpains, calpastatin and spectrin cleavage in the brain during the pathology of fatal murine cerebral malaria.	neuronal calpains appear to be activated uncontrollably by sustained elevation of cytosolic calcium levels under pathological conditions as well as neurodegenerative diseases. in the present study, we have characterized calpain activation in cytosolic extract of mice cerebral cortex and cerebellum using an experimental model of fatal murine cerebral malaria (fmcm). pathology of fmcm resulted in the increase in activity of calpains in both cerebral cortex and cerebellum. western blot analysis rev ...	2006	16236382
severe malarial anemia of low parasite burden in rodent models results from accelerated clearance of uninfected erythrocytes.	severe malarial anemia (sma) is the most frequent life-threatening complication of malaria and may contribute to the majority of malarial deaths worldwide. to explore the mechanisms of pathogenesis, we developed a novel murine model of sma in which parasitemias peaked around 1.0% of circulating red blood cells (rbcs) and yet hemoglobin levels fell to 47% to 56% of baseline. the severity of anemia was independent of the level of peak or cumulative parasitemia, but was linked kinetically to the du ...	2006	16210332
mutational analysis of the gpi-anchor addition sequence from the circumsporozoite protein of plasmodium.	the plasma membrane of plasmodium sporozoites is uniformly covered by the glycosylphosphatidylinositol (gpi)-anchored circumsporozoite (cs) protein. sporozoites form in the mosquito midgut through a budding process that occurs within a multinucleate oocyst underneath the basal lamina of the gut. earlier genetic studies established that normal sporozoite development requires cs. mutant parasites lacking cs [cs (-)] do not form sporozoites. ultrastructural analysis of the oocysts from these parasi ...	2005	16207248
plasmodium berghei: effect of protease inhibitors during gametogenesis and early zygote development.	plasmodium berghei: the effect of five protease inhibitors, tpck, tlck, pmsf, leupeptin, and 1,10-phenanthroline on in vitro gametogenesis and early zygote development of p. berghei was investigated. pmsf and leupeptin showed no effect. cysteine/serine protease inhibitors tpck/tlck at concentrations of 75 and 100 microm were effective on inhibiting exflagellation center formation, and this effect was reversible with the addition of l-cysteine. exflagellation center formation was most effectively ...	2005	16198343
performance of flow cytometric analysis for the micronucleus assay--a reconstruction model using serial dilutions of malaria-infected cells with normal mouse peripheral blood.	to confirm the performance and statistical power of a flow cytometric method for scoring micronucleated erythrocytes, reconstruction experiments were performed. for these investigations, peripheral blood erythrocytes from untreated mice, with a micronucleated erythrocyte frequency of approximately 0.1% were combined with known quantities of plasmodium berghei (malaria) infected mouse erythrocytes. these cells had an infected erythrocyte frequency of approximately 0.7%, and mimic the dna content ...	2006	16188876
plasmodium berghei resists killing by reactive oxygen species.	reactive oxygen species (ros) are widely believed to kill malarial parasites. c57bl/6 mice injected with p. berghei inocula incubated with supraphysiological doses of no (< or =150 microm) or with peroxynitrite (220 microm), however, exhibited parasitemia similar to that seen with those given control inocula, and there was no difference in disease development. only treatment of inocula with no doses nearing saturation (> or =1.2 mm) resulted in no detectable parasitemia in the recipients; flow c ...	2005	16177347
synergistic antimalarial activity of ketones with rufigallol and vitamin c.	malaria remains a major cause of human morbidity and mortality worldwide. plasmodium falciparum, the most virulent of the 4 human plasmodium species causing malaria, is potentially life threatening, is increasing in prevalence and is becoming even more resistant to in-use drugs. in light of the growing problem of multi-drug resistance to malarial parasites, the development of new drugs or the use of a combination therapy is of primary importance. a previous report describes a remarkable synergis ...	2005	16174410
in vivo antimalarial activities of extracts from amaranthus spinosus l. and boerhaavia erecta l. in mice.	extracts obtained from two burkinabe folk medicine plants, spiny amaranth (amaranthus spinosus l., amaranthaceae) and erect spiderling (boerhaavia erecta l., nyctagynaceae) were screened for antimalarial properties with the aim of testing the validity of their traditional uses. the plant extracts showed significant antimalarial activities in the 4-day suppressive antimalarial assay in mice inoculated with red blood cells parasitized with plasmodium berghei berghei. we obtained values for ed(50) ...	2006	16171960
selectively impaired cd8+ but not cd4+ t cell cycle arrest during priming as a consequence of dendritic cell interaction with plasmodium-infected red cells.	individuals living in malaria-endemic areas show generally low t cell responses to malaria ags. in this study, we show murine dendritic cell (dc) interaction with parasitized erythrocytes (prbc) arrested their maturation, resulting in impaired ability to stimulate naive, but not recall t cell responses in vitro and in vivo. moreover, within the naive t cell population, prbc-treated dc were selectively deficient in priming cd8(+) but not cd4(+) t cells. indeed, dc that had taken up prbc were show ...	2005	16148095
analysis of immune response patterns in naïve and plasmodium berghei-infected young rats following a ferroquine treatment.	the direct antimalarial activity of ferroquine (fq, ssr97193), a chloroquine (cq) derivative, is well established. to determine whether the fq anti-parasite activity affects the host immune properties, we have investigated its effect on several immunological parameters in young rats infected with plasmodium berghei and compared it with that of cq. in uninfected young rats, treatment with either drug did not show any impairment in the cellular distribution of spleen cells in their response to mit ...	2005	16140302
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
how i became a biochemist.		2005	16036582
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
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
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
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
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
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 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
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
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