Publications

role for the plasmodium sporozoite-specific transmembrane protein s6 in parasite motility and efficient malaria transmission.	malaria transmission occurs by intradermal deposition of plasmodium sporozoites during the infectious bite of a female anopheles mosquito. after formation in midgut-associated oocysts sporozoites actively enter mosquito salivary glands and subsequently invade host hepatocytes where they transform into clinically silent liver stages. to date, two sporozoite-specific transmembrane proteins have been identified that perform vital functions in natural malaria transmission. the sporozoite invasin tra ...	2009	19016774
the n-terminal domain of plasmodium falciparum circumsporozoite protein represents a target of protective immunity.	the n-terminal domain of the circumsporozoite protein (csp) has been largely neglected in the search for a malaria vaccine in spite of being a target of inhibitory antibodies and protective t cell responses in mice. thus, in order to develop this region as a vaccine candidate to be eventually associated with other candidates and, in particular, with the very advanced c-terminal counterpart, synthetic constructs representing n- and c-terminal regions of plasmodium falciparum and plasmodium berghe ...	2009	18984024
analysis of mutant plasmodium berghei parasites lacking expression of multiple pbccp genes.	plasmodium encodes a family of six secreted multi-domain adhesive proteins, termed pccps, which are released from gametocytes during emergence within the mosquito midgut. the expression and cellular localization of pccp proteins predict a role either in gametocyte development or within the mosquito midgut during the transition from gametes into the ookinete stage. however, mutant parasites lacking expression of any single pccp protein show a phenotype at the oocyst stage with a failure of oocyst ...	2009	18848846
growth-inhibitory effect of a fucoidan from brown seaweed undaria pinnatifida on plasmodium parasites.	the present study was undertaken to investigate the inhibitory effects of fucoidan, a sulfated polysaccharide isolated from the edible brown seaweed undaria pinnatifida, on the growth of plasmodium parasites. in order to assess the anti-malarial activity of fucoidan, growth inhibition activities were evaluated using cultured plasmodium falciparum parasites in vitro and on plasmodium berghei-infected mice in vivo. fucoidan significantly inhibited the invasion of erythrocytes by p. falciparum mero ...	2009	18791738
in vivo antiplasmodial activity of 11(13)-dehydroivaxillin from carpesium ceruum.	the whole plants of carpesium genus are used in traditional medicine as anti-pyretic, analgesic and vermifugic, including a topical application for sores and inflammation. a previous study on carpesium genus suggested that the antiplasmodial activity against plasmodium falciparum was due to the existence of 11(13)- dehydroivaxillin (ddv) from etoac extracts of c. ceruum (compositae). here, the antimalarial activity of ddv was evaluated against plasmodium berghei in mice. the ld(50) of the compou ...	2009	18608780
synthesis and antimalarial activity of pyrazolo and pyrimido benzothiazine dioxide derivatives.	a series of phenylsubstituted pyrazolo and pyrimido benzothiazine dioxide derivatives were synthesized and investigated for their abilities to inhibit beta-hematin formation, hemoglobin hydrolysis and in vivo for their antimalarial efficacy in rodent plasmodium berghei. compounds 3-amino-7-chloro-9-(2'-methylphenyl)-1,9-dihydro-pyrazolo-[4,3-b]benzothiazine 4,4-dioxide 2b and 2,4-diamino-8-chloro-10h-phenyl-pyrimido-[5,4-b]benzothiazine 5,5-dioxide 3a were the most promising as inhibitors of hem ...	2009	18835067
modification of oxidative status in plasmodium berghei-infected erythrocytes by e-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline compared to chloroquine.	e-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline (iq) is a new quinoline derivative which has been reported as a haemoglobin degradation and ss-haematin formation inhibitor. the haemoglobin proteolysis induced by plasmodium parasites represents a source of amino acids and haeme, leading to oxidative stress in infected cells. in this paper, we evaluated oxidative status in plasmodium berghei-infected erythrocytes in the presence of iq using chloroquine (cq) as a control. a ...	2009	19876558
determination of the expression of lymphocyte surface markers and cytokine levels in a mouse model of plasmodium berghei.	this study aimed to determine the changes in lymphocyte surface markers and cytokine profiles during a malarial infection in a mouse model of malaria. mononuclear cells obtained from the spleens of the mice infected with plasmodium berghei (p. berghei) were stained with anti-mouse cd3, anti-mouse cd4, anti-mouse cd8, anti-mouse cd19, anti-mouse cd152, anti-mouse pan natural killer (nk), anti-mouse cd80 monoclonal antibodies and expression of surface markers was evaluated by flow cytometry. in th ...	2009	19845111
limited role of cd4+foxp3+ regulatory t cells in the control of experimental cerebral malaria.	cerebral malaria (cm) associated with plasmodium berghei anka (pba) infection is an accepted model of human cm. cm during pba infection critically depends on sequestration of t cells into the brain. several studies aimed to address the role of regulatory t cells (t(reg)) in modulating this pathogenic t cell response. however, these studies are principally hampered due to the fact that until recently no reagents were available to deplete foxp3(+) t(reg) specifically. to study the function of t(re ...	2009	19890049
a role for immune responses against non-cs components in the cross-species protection induced by immunization with irradiated malaria sporozoites.	immunization with irradiated plasmodium sporozoites induces sterile immunity in rodents, monkeys and humans. the major surface component of the sporozoite the circumsporozoite protein (cs) long considered as the antigen predominantly responsible for this immunity, thus remains the leading candidate antigen for vaccines targeting the parasite's pre-erythrocytic (pe) stages. however, this role for cs was questioned when we recently showed that immunization with irradiated sporozoites (irrspz) of a ...	2009	19890387
accelerated clearance of plasmodium-infected erythrocytes in sickle cell trait and annexin-a7 deficiency.	the course of malaria does not only depend on the virulence of the parasite plasmodium but also on properties of host erythrocytes. here, we show that infection of erythrocytes from human sickle cell trait (hba/s) carriers with ring stages of p. falciparum led to significantly enhanced pge(2) formation, ca(2+) permeability, annexin-a7 degradation, phosphatidylserine (ps) exposure at the cell surface, and clearance by macrophages. p. berghei-infected erythrocytes from annexin-a7-deficient (annexi ...	2009	19910682
new 1-aryl-3-substituted propanol derivatives as antimalarial agents.	this paper describes the synthesis and in vitro antimalarial activity against a p. falciparum 3d7 strain of some new 1-aryl-3-substituted propanol derivatives. twelve of the tested compounds showed an ic(50) lower than 1 microm. these compounds were also tested for cytotoxicity in murine j774 macrophages. the most active compounds were evaluated for in vivo activity against p. berghei in a 4-day suppressive test. compound 12 inhibited more than 50% of parasite growth at a dose of 50 mg/kg/day. i ...	2009	19924051
visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging.	the quantitative analysis of plasmodium development in the liver in laboratory animals in cultured cells is hampered by low parasite infection rates and the complicated methods required to monitor intracellular development. as a consequence, this important phase of the parasite's life cycle has been poorly studied compared to blood stages, for example in screening anti-malarial drugs. here we report the use of a transgenic p. berghei parasite, pbgfp-luc(con), expressing the bioluminescent report ...	2009	19924309
a nonadjuvanted polypeptide nanoparticle vaccine confers long-lasting protection against rodent malaria.	we have designed and produced a prototypic malaria vaccine based on a highly versatile self-assembling polypeptide nanoparticle (sapn) platform that can repetitively display antigenic epitopes. we used this platform to display a tandem repeat of the b cell immunodominant repeat epitope (dppppnpn)(2)d of the malaria parasite plasmodium berghei circumsporozoite protein. administered in saline, without the need for a heterologous adjuvant, the sapn construct p4c-mal conferred a long-lived, protecti ...	2009	19915055
discovery of plasmodium modulators by genome-wide analysis of circulating hemocytes in anopheles gambiae.	insect hemocytes mediate important cellular immune responses including phagocytosis and encapsulation and also secrete immune factors such as opsonins, melanization factors, and antimicrobial peptides. however, the molecular composition of these important immune cells has not been elucidated in depth, because of their scarcity in the circulating hemolymph, their adhesion to multiple tissues and the lack of primary culture methods to produce sufficient material for a genome-wide analysis. in this ...	2009	19940242
evaluation of the in vivo antimalarial activity of ethanolic leaf and stembark extracts of anthocleista djalonensis.	to evaluate the in vivo antimalarial activities of ethanolic leaf and stembark extracts of anthocleista djalonensis used traditionally as malarial remedy in southern nigeria in mice infected with plasmodium berghei berghei.	2009	20407556
the plasmodium hu homolog, which binds the plastid dna sequence-independent manner, is essential for the parasite's survival.	the nuclear genome of the human malaria parasite plasmodium falciparum encodes a homolog of the bacterial hu protein (pfhu). in this study, we characterised pfhu's physiological function. pfhu, which is targeted exclusively to the parasite's plastid, bound its natural target--the plastid dna--sequence-independently and complemented lack of hu in escherichia coli. the hu gene could not be knocked-out from the genome of plasmodium berghei, implying that hu is important for the parasite's survival. ...	2009	19358847
anopheles gambiae croquemort scrbq2, expression profile in the mosquito and its potential interaction with the malaria parasite plasmodium berghei.	the scavenger receptor family comprises transmembrane proteins involved in the recognition of polyanionic ligands. several studies have established that members of this family are involved both in immunity and in developmental processes. in drosophila melanogaster, one of the best characterized scavenger receptors is croquemort, which participates in the recognition of apoptotic cells in the embryo. although comparative genomic studies have revealed the presence of four orthologs of this recepto ...	2009	19366631
antimalarial activity of betulinic acid and derivatives in vitro against plasmodium falciparum and in vivo in p. berghei-infected mice.	malaria is one of the most important tropical diseases and mainly affects populations living in developing countries. reduced sensitivity of plasmodium sp. to formerly recommended antimalarial drugs places an increasing burden on malaria control programs as well as on national health systems in endemic countries. the present study aims to evaluate the antimalarial activity of betulinic acid and its derivative compounds, betulonic acid, betulinic acid acetate, betulinic acid methyl ester, and bet ...	2009	19367418
nanoencapsulation increases quinine antimalarial efficacy against plasmodium berghei in vivo.	the aims of this work were to develop quinine (qn)-loaded nanocapsules, to evaluate their efficacy in vivo and to determine their pharmacokinetics and erythrocyte partition coefficient. plasmodium berghei-infected wistar rats were used to evaluate the efficacy of qn-loaded nanocapsules using different dosing regimens. pharmacokinetics was evaluated after intravenous administration of free or nanoencapsulated qn (25 mg/kg) to infected rats. the qn partition coefficient into p. berghei-infected er ...	2009	19369041
clonal conditional mutagenesis in malaria parasites.	we describe here an efficient method for conditional gene inactivation in malaria parasites that uses the flp/frt site-specific recombination system of yeast. the method, developed in plasmodium berghei, consists of inserting frt sites in the chromosomal locus of interest in a parasite clone expressing the flp recombinase via a developmental stage-specific promoter. using promoters active in mosquito midgut sporozoites or salivary gland sporozoites to drive expression of flp or its thermolabile ...	2009	19380117
molecular genetics and comparative genomics reveal rnai is not functional in malaria parasites.	techniques for targeted genetic disruption in plasmodium, the causative agent of malaria, are currently intractable for those genes that are essential for blood stage development. the ability to use rna interference (rnai) to silence gene expression would provide a powerful means to gain valuable insight into the pathogenic blood stages but its functionality in plasmodium remains controversial. here we have used various rna-based gene silencing approaches to test the utility of rnai in malaria p ...	2009	19380379
two c-type lectins cooperate to defend anopheles gambiae against gram-negative bacteria.	c-type lectins (ctls) are a family of proteins that share a common structural motif, the carbohydrate recognition domain, and may act as receptors in pathogen recognition. indeed, some vertebrate ctls, particularly the collectins, are unequivocally implicated in the innate immune response to certain microbes. although studies in insects and other invertebrates have described ctl activation of effector immune responses in vitro, the contribution of these ctls to immune defenses in vivo is still p ...	2009	19380589
piperaquine pharmacodynamics and parasite viability in a murine malaria model.	piperaquine (pq) is an important partner drug in antimalarial combination treatments, but the long half-life of pq raises concerns about drug resistance. our aim was to investigate the extended antimalarial effect of pq in a study of drug efficacy, reinoculation outcomes, and parasite viability after the administration of a single dose of pq in the murine malaria model. initially, male swiss mice were inoculated with plasmodium berghei and at 64 h after parasite inoculation were given pq phospha ...	2009	19380600
kinetics of mosquito-injected plasmodium sporozoites in mice: fewer sporozoites are injected into sporozoite-immunized mice.	malaria is initiated when the mosquito introduces sporozoites into the skin of a mammalian host. to successfully continue the infection, sporozoites must invade blood vessels in the dermis and be transported to the liver. a significant number of sporozoites, however, may enter lymphatic vessels in the skin or remain in the skin long after the mosquito bite. we have used fluorescence microscopy of plasmodium berghei sporozoites expressing a fluorescent protein to evaluate the kinetics of sporozoi ...	2009	19390607
rosiglitazone modulates the innate immune response to plasmodium falciparum infection and improves outcome in experimental cerebral malaria.	for severe malarial syndromes such as cerebral malaria, adverse clinical outcomes are often mediated by the immune system rather than caused by the parasite directly. however, few therapeutic agents have been developed to modulate the host's immunopathological responses to infection. here, we report that the peroxisome proliferator-activated receptor gamma (ppargamma) agonist rosiglitazone modulated the host response to malaria by enhancing phagocytic clearance of malaria-parasitized erythrocyte ...	2009	19392627
antiplasmodial and antitrypanosomal activity of bicyclic amides and esters of dialkylamino acids.	several bicyclic amides and esters of dialkylamino acids were prepared. their activities against a multiresistant strain of plasmodium falciparum and against trypanosoma brucei rhodesiense (stib 900) were examined. structure-activity relationships were discussed. particularly the ester compounds showed good antiplasmodial and antitrypanosomal activity and a single compound was tested in vivo against plasmodium berghei.	2009	19395265
disruption of nod-like receptors alters inflammatory response to infection but does not confer protection in experimental cerebral malaria.	research relating to host inflammatory processes during malaria infection has focused on toll-like receptors, membrane-bound receptors implicated in innate sensing, and phagocytosis of parasitized erythrocytes by host cells. this is the first study to examine the role of nod proteins, members of the nod-like receptor (nlr) family of cytoplasmic proteins involved in pathogen recognition, in a murine model of cerebral malaria (plasmodium berghei anka, pba). here, we find that nod1nod2(-/-) mice in ...	2009	19407112
[role of histamine and histamine receptors in the pathogenesis of malaria].	a hallmark of the host response to plasmodium parasite is an inflammatory reaction characterized by elevated histaminemia levels. since histamine, which acts through four different receptors and which synthesis is under the control of the histidine decarboxylase (hdc), is endowed with pro-inflammatory and immunosuppressive activities, we hypothesized that this vaso-active amine may participe to malaria pathogenesis. combining genetic and pharmacologic approaches by using h1r(-/-), h2r(-/-), h3r( ...	2009	19409190
rate of red blood cell destruction varies in different strains of mice infected with plasmodium berghei-anka after chronic exposure.	severe malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses. thus the following has been thought to be involved: auto-immune-mediated mechanisms of uninfected red blood cell destruction, and host genetic factors to explain the differences in individual responses under the same malaria transmission. in this study, the extent of red blood cell (rbc) destruction in different strains of s ...	2009	19416511
localisation and timing of expression of putative plasmodium berghei rhoptry proteins in merozoites and sporozoites.	invasive forms of apicomplexan parasites contain secretory organelles (which may include micronemes, rhoptries or dense granules), the contents of which mediate invasion of host cells. only few rhoptry proteins have been identified in plasmodium and then only in merozoites and none in the sporozoite or ookinete. epitope-tagged proteins (with either green fluorescent protein or c-myc) were used to analyse the expression and cellular localisation of a known plasmodium rhoptry protein (rap2/3) and ...	2009	19428669
lisp1 is important for the egress of plasmodium berghei parasites from liver cells.	most apicomplexa are obligatory intracellular parasites that multiply inside a so-called parasitophorous vacuole (pv) formed upon parasite entry into the host cell. plasmodium, the agent of malaria and the apicomplexa most deadly to humans, multiplies in both hepatocytes and erythrocytes in the mammalian host. although much has been learned on how apicomplexa parasites invade host cells inside a pv, little is known of how they rupture the pv membrane and egress host cells. here, we characterize ...	2009	19438514
egress of plasmodium berghei gametes from their host erythrocyte is mediated by the mdv-1/peg3 protein.	malaria parasites invade erythrocytes of their host both for asexual multiplication and for differentiation to male and female gametocytes - the precursor cells of plasmodium gametes. for further development the parasite is dependent on efficient release of the asexual daughter cells and of the gametes from the host erythrocyte. how malarial parasites exit their host cells remains largely unknown. we here report the characterization of a plasmodium berghei protein that is involved in egress of b ...	2009	19438517
azathioprine favourably influences the course of malaria.	azathioprine triggers suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. eryptosis may accelerate the clearance of plasmodium-infected erythrocytes. the present study thus explored whether azathioprine influences eryptosis of plasmodium-infected erythrocytes, development of parasitaemia and thus the course of malaria.	2009	19442289
the high throughput sequence annotation service (ht-sas) - the shortcut from sequence to true medline words.	advances in high-throughput technologies available to modern biology have created an increasing flood of experimentally determined facts. ordering, managing and describing these raw results is the first step which allows facts to become knowledge. currently there are limited ways to automatically annotate such data, especially utilizing information deposited in published literature.	2009	19445703
hundreds of microsatellites for genotyping plasmodium yoelii parasites.	genetic crosses have been employed to study various traits of rodent malaria parasites and to locate loci that contribute to drug resistance, immune protection, and disease virulence. compared with human malaria parasites, genetic crossing of rodent malaria parasites is more easily performed; however, genotyping methods using microsatellites (mss) or large-scale single nucleotide polymorphisms (snps) that have been widely used in typing plasmodium falciparum are not available for rodent malaria ...	2009	19450732
automated classification of plasmodium sporozoite movement patterns reveals a shift towards productive motility during salivary gland infection.	the invasive stages of malaria and other apicomplexan parasites use a unique motility machinery based on actin, myosin and a number of parasite-specific proteins to invade host cells and tissues. the crucial importance of this motility machinery at several stages of the life cycle of these parasites makes the individual components potential drug targets. the different stages of the malaria parasite exhibit strikingly diverse movement patterns, likely reflecting the varied needs to achieve succes ...	2009	19455538
recrudescent plasmodium berghei from pregnant mice displays enhanced binding to the placenta and induces protection in multigravida.	pregnancy-associated malaria (pam) is associated with placenta pathology and poor pregnancy outcome but the mechanisms that control the malaria parasite expansion in pregnancy are still poorly understood and not amenable for study in human subjects. here, we used a set of new tools to re-visit an experimental mouse model of pregnancy-induced malaria recrudescence, balb/c with chronic plasmodium berghei infection. during pregnancy 60% of the pre-exposed primiparous females showed pregnancy-induce ...	2009	19461965
an essential role for the plasmodium nek-2 nima-related protein kinase in the sexual development of malaria parasites.	the molecular control of cell division and development in malaria parasites is far from understood. we previously showed that a plasmodium gametocyte-specific nima-related protein kinase, nek-4, is required for completion of meiosis in the ookinete, the motile form that develops from the zygote in the mosquito vector. here, we show that another nima-related kinase, pfnek-2, is also predominantly expressed in gametocytes, and that pfnek-2 is an active enzyme displaying an in vitro substrate prefe ...	2009	19491095
going live: a comparative analysis of the suitability of the rfp derivatives redstar, mcherry and tdtomato for intravital and in vitro live imaging of plasmodium parasites.	fluorescent proteins have proven to be important tools for in vitro live imaging of parasites and for imaging of parasites within the living host by intravital microscopy. we observed that a red fluorescent transgenic malaria parasite of rodents, plasmodium berghei-redstar, is suitable for in vitro live imaging experiments but bleaches rapidly upon illumination in intravital imaging experiments using mice. we have therefore generated two additional transgenic parasite lines expressing the novel ...	2009	19492329
plasmodium berghei-infection induces volume-regulated anion channel-like activity in human hepatoma cells.	parasite infection can lead to alterations in the permeability of host plasma membranes. presented here is the first demonstration that this phenomenon occurs in plasmodium-infected liver cells. using the whole-cell patch-clamp technique, volume-regulated anion channel (vrac) activity was characterized in huh-7 cells (a human hepatoma cell line) before and after infection with plasmodium berghei. consistent with the presence of vracs, hypotonic bath solution induced large ion currents in huh-7 c ...	2009	19496788
genome-wide transcriptomic profiling of anopheles gambiae hemocytes reveals pathogen-specific signatures upon bacterial challenge and plasmodium berghei infection.	the mosquito anopheles gambiae is a major vector of human malaria. increasing evidence indicates that blood cells (hemocytes) comprise an essential arm of the mosquito innate immune response against both bacteria and malaria parasites. to further characterize the role of hemocytes in mosquito immunity, we undertook the first genome-wide transcriptomic analyses of adult female an. gambiae hemocytes following infection by two species of bacteria and a malaria parasite.	2009	19500340
malaria downmodulates mrna expression and catalytic activities of cyp1a2, 2e1 and 3a11 in mouse liver.	it has been reported that malaria reduces cytochrome-p450 (cyp) content and monooxygenase activities in the mammalian host liver. the mechanism by which malaria modulates cyp activities, however, remains unclear. in this study we found that activities of ethoxy- and benzyloxy-resorufin-o-dealkylases, p-nitrophenol-hydroxylase and erythromycin-n-demethylase (mediated by cyp1a, 2b, 2e1 and 3a, respectively) were depressed, while uridine-glucuronosyl-transferase (a phase 2 enzyme) was unaltered in ...	2009	19501084
novel antimicrobial peptides isolated from skin secretions of the mexican frog hyla eximia.	in this work, we describe the original characterization of peptides and proteins present in the skin secretions of the mexican amphibian hyla eximia. to this purpose, a novel water/dark extraction method, as well as the classic electrical stimulation procedure, was applied in order to extract the skin secretion. two novel antimicrobial peptides he-1 and he-2 were sequenced. in addition, a molecular mass fingerprint revealed more than one hundred different molecules. eight peptides in homogeneous ...	2009	19508207
synthesis and antimalarial activities of optically active labdane-type diterpenes.	an efficient method for the synthesis of optically active labdane-type diterpenes from (+)-manool 8 is described. we prepared the natural labdane-type diterpene 5 via key intermediate peroxide 9, and synthetic hydroxybutenolides 6 and 7 via a furan photosensitised oxygenation reaction of labdafuran (14). compounds 5, 6, 7 and 9 were evaluated as inhibitors of the beta-haematin formation and globin proteolysis, and then were assayed in a malarial murine model. compound 9 was the most promising co ...	2009	19521902
methotrexate and aminopterin lack in vivo antimalarial activity against murine malaria species.	the antifolate anticancer drug methotrexate (mtx) has potent activity against plasmodium falciparum in vitro. experience of its use in the treatment of rheumatoid arthritis indicates that it could be safe and efficacious for treating malaria. we sought to establish a murine malaria model to study the mechanism of action and resistance of mtx and its analogue aminopterin (amp). we used plasmodium berghei, plasmodium yoelii yoelii, plasmodium chabaudi and plasmodium vinckei. none of these species ...	2009	19527714
host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events.	plasmodium sporozoites migrate to the liver where they traverse several hepatocytes before invading the one inside which they will develop and multiply into thousands of merozoites. although this constitutes an essential step of malaria infection, the requirements of plasmodium parasites in liver cells and how they use the host cell for their own survival and development are poorly understood.	2009	19534804
in-depth validation of acridine orange staining for flow cytometric parasite and reticulocyte enumeration in an experimental model using plasmodium berghei.	flow cytometry is potentially an effective method for counting malaria parasites, but inconsistent results have hampered its routine use in rodent models. a published two-channel method using acridine orange offers clear discrimination between the infected and uninfected erythrocytes. however, preliminary studies showed concerns when dealing with plasmodium berghei-infected blood samples with high numbers of reticulocytes. in hyperparasitemic or chronic p. berghei infection, enhanced erythropoie ...	2009	19545567
histamine h(3) receptor-mediated signaling protects mice from cerebral malaria.	histamine is a biogenic amine that has been shown to contribute to several pathological conditions, such as allergic conditions, experimental encephalomyelitis, and malaria. in humans, as well as in murine models of malaria, increased plasma levels of histamine are associated with severity of infection. we reported recently that histamine plays a critical role in the pathogenesis of experimental cerebral malaria (cm) in mice infected with plasmodium berghei anka. histamine exerts its biological ...	2009	19547708
gamma-glutamylcysteine synthetase from plasmodium berghei.	gamma-glutamylcysteine synthetase (l-glutamate-l-cysteine ligase, gamma-gcs, ec 6.3.2.2.), the rate limiting enzyme in glutathione biosynthetic pathway has been analysed in the asexual erythrocytic stages of rodent malaria parasite, plasmodium berghei and its host erythrocytes. cell-free parasite isolated by saponin lysis contained about 2 and 8 times higher activity of gamma-gcs compared to p. berghei-infected and normal mice erythrocytes respectively. subcellular fractionation revealed that th ...	2009	19567234
molecular adjuvants for malaria dna vaccines based on the modulation of host-cell apoptosis.	malaria represents a major global health problem but despite extensive efforts, no effective vaccine is available. various vaccine candidates have been developed that provide protection in animal models, such as a gene gun-delivered dna vaccine encoding the circumsporozoite protein (csp) of plasmodium berghei. a common shortcoming of most malaria vaccines is the requirement for multiple immunizations leaving room for improvement even for established vaccine candidates such as the csp-dna vaccine ...	2009	19576940
antiplasmodial activity of punica granatum l. fruit rind.	sun-dried rind of the immature fruit of punica granatum l. (punicaceae) (pg) is presently used as a herbal formulation (omaria) in orissa, india, for the therapy and prophylaxis of malaria. the aims of this study were (i) to assess in vitro the antiplasmodial activity of the methanolic extract, of a tannin enriched fraction and of compounds/metabolites of the antimalarial plant, (ii) to estimate the curative efficacy of the pg extracts and (iii) to explore the mechanism of action of the antiplas ...	2009	19577622
ethanolic extract of clerodendrum violaceum gürke leaves enhances kidney function in mouse model of malaria.	evaluation of the effects of daily oral administration of ethanolic extract of c. violaceum leaves (13 mg/kg body weight) for 5 days on some kidney function indices of uninfected and plasmodium berghei-infected mice was done on days 3, 8 and 14 post-infection. the indices studied include serum urea and creatinine concentrations with the specific activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase in the kidney. treatment of p. berghei-infected mice with et ...	2009	19579800
anti-malarial activity of 6-(8'z-pentadecenyl)-salicylic acid from viola websteri in mice.	petroleum ether extracts of viola websteri hemsl (violaceae) were reported to have anti-plasmodial activity against plasmodium falciparum in vitro, with this activity being largely attributable to 6-(8'z-pentadecenyl)-salicylic acid (6-sa).	2009	19583856
the interaction between dc and plasmodium berghei/chabaudi-infected erythrocytes in mice involves direct cell-to-cell contact, internalization and tlr.	early interactions between blood-stage plasmodium parasites and cells of the innate immune system are very important in shaping the adaptive immune response to malaria, and a number of studies have suggested that dc are responsible for this phenomenon. therefore, we examined the capacity of murine bm-derived dc to internalize parasites, be activated and produce cytokines upon in vitro interaction with murine erythrocytes infected with two different strains of rodent malaria parasites (plasmodium ...	2009	19585512
plasmodium berghei hap2 induces strong malaria transmission-blocking immunity in vivo and in vitro.	fertilization in plasmodium is a complex process that occurs in the gut of the female anopheles mosquito upon uptake of a bloodmeal. it requires the emergence of the gametocyte from the rbc and release of eight flagellate male gametes from each male cell, and subsequent fertilization of a similarly emerged immotile extracellular female macrogamete. previous studies have demonstrated that antibodies against male gamete surface proteins ingested from the blood of an infected and immunized host inh ...	2009	19596419
malaria ookinetes exhibit multiple markers for apoptosis-like programmed cell death in vitro.	abstract:	2009	19604379
addlp, a bacterial defensin-like peptide, exhibits anti-plasmodium activity.	antimicrobial defensins with the cysteine-stabilized alpha-helical and beta-sheet (csalphabeta) motif are widely distributed in three eukaryotic kingdoms. however, recent work suggests that bacteria could possess defensin-like peptides (dlps). here, we report recombinant expression, in vitro folding, structural and functional characterization of a dlp from the myxobacterium anaeromyxobacter dehalogenans (addlp). circular dichroism analysis indicates that recombinant addlp adopts a typical struct ...	2009	19615342
evaluation of in vivo antimalarial activities of ethanolic leaf and seed extracts of telfairia occidentalis.	the leaves and seeds of telfairia occidentalis are used as vegetables in making soups in southern nigeria. in this study, we investigated the antimalarial activity of leaf and seed extracts in vivo in mice infected with plasmodium berghei berghei during early and established infections. t. occidentalis leaf extract (250-750 mg/kg/day) exhibited antiplasmodial activity both in the 4-day early infection test and in established infection with a marked increase of the mean survival time, which, howe ...	2009	19627216
mosquito immune responses and compatibility between plasmodium parasites and anopheline mosquitoes.	functional screens based on dsrna-mediated gene silencing identified several anopheles gambiae genes that limit plasmodium berghei infection. however, some of the genes identified in these screens have no effect on the human malaria parasite plasmodium falciparum; raising the question of whether different mosquito effector genes mediate anti-parasitic responses to different plasmodium species.	2009	19643026
malarial hemozoin is a nalp3 inflammasome activating danger signal.	background: characteristic symptoms of malaria include recurrent fever attacks and neurodegeneration, signs that are also found in patients with a hyperactive nalp3 inflammasome. plasmodium species produce a crystal called hemozoin that is generated by detoxification of heme after hemoglobin degradation in infected red blood cells. thus, we hypothesized that hemozoin could activate the nalp3 inflammasome, due to its particulate nature reminiscent of other inflammasome-activating agents. methodol ...	2009	19652710
antiplasmodial activity of root extract and fractions of croton zambesicus.	antiplasmodial activity of root extract and fractions of croton zambesicus were evaluated to ascertain the folkloric claim of its antimalarial activity and elucidate its antiplasmodial mechanism of action.	2009	18996464
highly efficient subcloning of rodent malaria parasites by injection of single merosomes or detached cells.	this protocol describes a method for obtaining rodent plasmodium parasite clones with high efficiency, which takes advantage of the normal course of plasmodium in vitro exoerythrocytic development. at the completion of development, detached cells/merosomes form, which contain hundreds to thousands of merozoites. as all parasites within a single detached cell/merosome derive from the same sporozoite, we predicted them to be genetically identical. to prove this, hepatoma cells were infected simult ...	2009	19745825
altered nucleotide receptor expression in a murine model of cerebral malaria.	in cerebral malaria, the most severe complication of malaria, both neurotransmission mechanisms and energy metabolism are affected. to understand how metabolic changes modify neurotransmission, we examined p2 receptor expression in a murine model of cerebral malaria. quantitative polymerase chain reaction experiments revealed that parasite deposition was greatest in the cerebellum, compared with other areas of the brain, suggesting a correlation between brain parasitemia and loss of control of m ...	2009	19758097
the ig domain protein cd9p-1 down-regulates cd81 ability to support plasmodium yoelii infection.	invasion of hepatocytes by plasmodium sporozoites is a prerequisite for establishment of a malaria natural infection. the molecular mechanisms underlying sporozoite invasion are largely unknown. we have previously reported that cd81 is required on hepatocytes for infection by plasmodium falciparum and plasmodium yoelii sporozoites. cd81 belongs to the tetraspanin superfamily of transmembrane proteins. by interacting with each other and with other transmembrane proteins, tetraspanins may play a r ...	2009	19762465
a cyclic gmp signalling module that regulates gliding motility in a malaria parasite.	the ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. the regulation of gliding motility is poorly understood. through genetic interaction studies we here describe a signalling module that identifies guanosine 3', 5'-cyclic monophosphate (cgmp) as an important second messenger regulating ookinete differentiation and mot ...	2009	19779564
structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues.	based on the indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3) and isoneocryptolepine (4), used as lead compounds for new antimalarial agents, a series of tricyclic and bicyclic analogues, including carbolines, azaindoles, pyrroloquinolines and pyrroloisoquinolines was synthesized and biologically evaluated. none of the bicyclic compounds was significantly active against the chloroquine-resistant strain plasmodium falciparum k1, in contrast to the tricyclic der ...	2009	19781948
dissecting the genetic basis of resistance to malaria parasites in anopheles gambiae.	the ability of anopheles gambiae mosquitoes to transmit plasmodium parasites is highly variable between individuals. however, the genetic basis of this variability has remained unknown. we combined genome-wide mapping and reciprocal allele-specific rna interference (rasrnai) to identify the genomic locus that confers resistance to malaria parasites and demonstrated that polymorphisms in a single gene encoding the antiparasitic thioester-containing protein 1 (tep1) explain a substantial part of t ...	2009	19797663
statins fail to improve outcome in experimental cerebral malaria and potentiate toll-like receptor-mediated cytokine production by murine macrophages.	cerebral malaria is responsible for a large proportion of the estimated one million deaths caused by plasmodium falciparum malaria annually. this disease is associated with excessive pro-inflammatory cytokine production resulting from dysregulated host responses to infection. on the basis of reports indicating potent activity against host-mediated inflammatory disorders such as sepsis, we examined the activity of statins (3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors) on malaria-ass ...	2009	19815878
anopheles mortality is both age- and plasmodium-density dependent: implications for malaria transmission.	daily mortality is an important determinant of a vector's ability to transmit pathogens. original simplifying assumptions in malaria transmission models presume vector mortality is independent of age, infection status and parasite load. previous studies illustrate conflicting evidence as to the importance of plasmodium-induced vector mortality, but very few studies to date have considered the effect of infection density on mosquito survival.	2009	19822012
the crystal structures of macrophage migration inhibitory factor from plasmodium falciparum and plasmodium berghei.	malaria, caused by plasmodium falciparum and related parasites, is responsible for millions of deaths each year, mainly from complications arising from the blood stages of its life cycle. macrophage migration inhibitory factor (mif), a protein expressed by the parasite during these stages, has been characterized in mammals as a cytokine involved in a broad spectrum of immune responses. it also possesses two catalytic activities, a tautomerase and an oxidoreductase, though the physiological signi ...	2009	19827093
preliminary studies on the effects of orally-administered transforming growth factor-beta on protozoan diseases in mice.	transforming growth factor beta-1 (tgf-beta1) is a pleiotropic cytokine with both pro- and antiinflammatory properties, depending on its environment and concentration. the present study evaluated the effects of orally-delivered tgf-beta1 on mice parenterally-infected with various protozoan parasites. we report that while orally-administered tgf-beta1 seems to confer partial protection against murine chronic babesiosis and acute trypanosomosis, no beneficial clinical effects were observed against ...	2009	19827745
structure-activity relationship studies of manzamine a: amidation of positions 6 and 8 of the beta-carboline moiety.	twenty manzamine amides were synthesized and evaluated for in vitro antimalarial and antimicrobial activities. the amides of manzamine a (1) showed significantly reduced cytotoxicity against vero cells, although were less active than 1. the structure-activity analysis showed that linear, short alkyl groups adjacent to the amide carbonyl at position 8 are favored for antimalarial activity, while bulky and cyclic groups at position 6 provided the most active amides. most of the amides showed poten ...	2009	19833520
signalling in malaria parasites. the malsig consortium.	depending on their developmental stage in the life cycle, malaria parasites develop within or outside host cells, and in extremely diverse contexts such as the vertebrate liver and blood circulation, or the insect midgut and hemocoel. cellular and molecular mechanisms enabling the parasite to sense and respond to the intra- and the extra-cellular environments are therefore key elements for the proliferation and transmission of plasmodium, and therefore are, from a public health perspective, stra ...	2009	19839262
primaquine dipeptide derivatives bearing an imidazolidin-4-one moiety at the n-terminus as potential antimalarial prodrugs.	primaquine dipeptide derivatives bearing an imidazolidin-4-one moiety at the n-terminus were synthesized and evaluated as potential transmission-blocking antimalarial prodrugs. all compounds were hydrolyzed to the parent dipeptide derivative of primaquine in neutral and basic solutions, with half lives ranging from 0.7 to 31 h at 37 degrees c, depending on the nature of the substituents present in the imidazolidin-4-one moiety and in the c-terminal amino acid directly coupled to primaquine. the ...	2009	19232784
variant-specific immunity to plasmodium berghei in pregnant mice.	we have investigated the immunological basis of pregnancy-related plasmodium berghei recrudescence in immune mice with substantial preexisting immunity. specifically, we examined the relevance of this experimental model to the study of pregnancy-associated malaria (pam) caused by p. falciparum in women with substantial preexisting protective immunity. we used mice with immunity induced prior to pregnancy and employed flow cytometry to assess their levels of immunoglobulin g (igg) recognizing ant ...	2009	19237516
polymeric linear peptide chimeric vaccine-induced antimalaria immunity is associated with enhanced in vitro antigen loading.	immunization of mice with plasmodium berghei or plasmodium yoelii synthetic linear peptide chimeras (lpcs) based on the circumsporozoite protein protects against experimental challenge with viable sporozoites. the immunogenicity of lpcs is significantly enhanced by spontaneous polymerization. to better understand the antigenic properties of polymeric antimalarial peptides, we studied the immune responses elicited in mice immunized with a polymer or a monomer of a linear peptide construct specifi ...	2009	19237530
glatiramer acetate reduces the risk for experimental cerebral malaria: a pilot study.	cerebral malaria (cm) is associated with high mortality and morbidity caused by a high rate of transient or persistent neurological sequelae. studies on immunomodulatory and neuroprotective drugs as ancillary treatment in murine cm indicate promising potential. the current study was conducted to evaluate the efficacy of glatiramer acetate (ga), an immunomodulatory drug approved for the treatment of relapsing remitting multiple sclerosis, in preventing the death of c57bl/6j mice infected with pla ...	2009	19250545
influence of paclitaxel on parasitemia and survival of plasmodium berghei infected mice.	paclitaxel triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. eryptosis of infected erythrocytes may delay development of parasitemia and thus favourably influence the course of malaria. the present study explored whether paclitaxel influences in vitro parasite growth and eryptosis of plasmodium falciparum infected human erythrocytes and in vivo parasitemia and survival of plasmodium berghei infected mi ...	2009	19255513
paternal effect of the nuclear formin-like protein misfit on plasmodium development in the mosquito vector.	malaria parasites must undergo sexual and sporogonic development in mosquitoes before they can infect their vertebrate hosts. we report the discovery and characterization of misfit, the first protein with paternal effect on the development of the rodent malaria parasite plasmodium berghei in anopheles mosquitoes. misfit is expressed in male gametocytes and localizes to the nuclei of male gametocytes, zygotes and ookinetes. gene disruption results in mutant ookinetes with reduced genome content, ...	2009	19662167
anopheles gambiae pgrplc-mediated defense against bacteria modulates infections with malaria parasites.	recognition of peptidoglycan (pgn) is paramount for insect antibacterial defenses. in the fruit fly drosophila melanogaster, the transmembrane pgn recognition protein lc (pgrp-lc) is a receptor of the imd signaling pathway that is activated after infection with bacteria, mainly gram-negative (gram-). here we demonstrate that bacterial infections of the malaria mosquito anopheles gambiae are sensed by the orthologous pgrplc protein which then activates a signaling pathway that involves the rel/nf ...	2009	19662170
ca/c1 peptidases of the malaria parasites plasmodium falciparum and p. berghei and their mammalian hosts--a bioinformatical analysis.	in genome-wide screens we studied ca/c1 peptidases of malaria-causing plasmodia and their hosts (man and mouse). for plasmodium falciparum and p. berghei, several new ca/c1 peptidase genes encoding proteases of the l- and b-family with specific promoter modules were identified. in addition, two new human ca/c1 peptidase loci and one new mouse gene locus were found; otherwise, the sets of ca/c1 peptidase genes in man and mouse seem to be complete now. in each species studied there is a multitude ...	2009	19663681
characterization of plasmodium falciparum calcium-dependent protein kinase 4.	in plasmodium berghei, the orthologous gene of p. falciparum calcium-dependent protein kinase 4 (pfcdpk4) was reported to be essential for the exflagellation of male gametocytes. to elucidate the role of pfcdpk4 in p. falciparum gametogenesis, we characterized the biological function of pfcdpk4 in vitro. pfcdpk4 was purified as a fusion protein that was labeled with [gamma-(32)p]atp; this labeling was then eliminated by phosphatase. phosphorylation activity of pfcdpk4 was eliminated when its put ...	2009	19666141
vital role for the plasmodium actin capping protein (cp) beta-subunit in motility of malaria sporozoites.	summary successful malaria transmission from the mosquito vector to the mammalian host depends crucially on active sporozoite motility. sporozoite locomotion and host cell invasion are driven by the parasite's own actin/myosin motor. a unique feature of this motor machinery is the presence of very short subpellicular actin filaments. therefore, f-actin stabilizing proteins likely play a central role in parasite locomotion. here, we investigated the role of the plasmodium berghei actin capping pr ...	2009	19682250
bioassay-guided fractionation and in vivo antiplasmodial effect of fractions of chloroform extract of artemisia maciverae linn.	in the search for new plant-derived anti-malarial compounds, chromatographic fractions of chloroform extract of whole plants of artemisia maciverae were tested in vivo using chloroquine resistant and chloroquine sensitive plasmodium berghei nk 65 infected swiss albino mice. one fraction and a sub-fraction of this were most active at 10/mg and cleared parasitemia in mice within 3 days. the different fractions and sub-fractions were tested with different reagents to determine the broad classes of ...	2009	19695214
pathogenic roles of cd14, galectin-3, and ox40 during experimental cerebral malaria in mice.	an in-depth knowledge of the host molecules and biological pathways that contribute towards the pathogenesis of cerebral malaria would help guide the development of novel prognostics and therapeutics. genome-wide transcriptional profiling of the brain tissue during experimental cerebral malaria (ecm ) caused by plasmodium berghei anka parasites in mice, a well established surrogate of human cerebral malaria, has been useful in predicting the functional classes of genes involved and pathways alte ...	2009	19710907
quantitative assessment of dna replication to monitor microgametogenesis in plasmodium berghei.	targeting the crucial step of plasmodium transition from vertebrate host to mosquito vector is a promising approach to eliminate malaria. uptake by the mosquito activates gametocytes within seconds, and in the case of male (micro) gametocytes leads to rapid dna replication and the release of eight flagellated gametes. we developed a sensitive assay to monitor p. berghei microgametocyte activation based on [(3)h]hypoxanthine incorporation into dna. optimal ph range and xanthurenic acid concentrat ...	2009	19712704
cd8 t cell immunity to plasmodium permits generation of protective antibodies after repeated sporozoite challenge.	individuals living in malaria endemic areas are subject to repeated infections yet fail to develop sterilizing immunity, however, immunization of mice with attenuated sporozoites or subunit vaccines has shown the ability to protect mice against a sporozoite challenge. we recently reported that mice primed with dendritic cells coated with the dominant circumsporozoite cd8 t cell epitope from plasmodium berghei followed by a boost with recombinant listeria monocytogenes expressing the same epitope ...	2009	19712771
construction of transgenic plasmodium berghei as a model for evaluation of blood-stage vaccine candidate of plasmodium falciparum chimeric protein 2.9.	the function of the 19 kda c-terminal region of the merozoite surface protein 1 (msp1-19) expressed by plasmodium has been demonstrated to be conserved across distantly related plasmodium species. the green fluorescent protein (gfp) is a reporter protein that has been widely used because it can be easily detected in living organisms by fluorescence microscopy and flow cytometry.	2009	19727400
glutathione reductase and thioredoxin reductase: novel antioxidant enzymes from plasmodium berghei.	malaria parasites adapt to the oxidative stress during their erythrocytic stages with the help of vital thioredoxin redox system and glutathione redox system. glutathione reductase and thioredoxin reductase are important enzymes of these redox systems that help parasites to maintain an adequate intracellular redox environment. in the present study, activities of glutathione reductase and thioredoxin reductase were investigated in normal and plasmodium berghei-infected mice red blood cells and th ...	2009	19967095
experimental splenectomies and malaria in mice.	to evaluate the importance of spleen in malaric infection in murino model, comparing the parasitemia and the titles of immunoglobulins in the different groups.	2009	20011827
screening of traditionally used plants for in vivo antimalarial activity in mice.	aqueous ethanol (80%) extracts of six plants used traditionally for treatment of malaria, vepris glomerata (f.hoffm.) engl (rutaceae), maranthus floribunda (bak.) f.white (chrysobalanaceae), strophanthus eminii asch. & pax ex pax (apocynaceae), cassia abbreviata oliv. (leguminosae) and caesalpinia bonducella l. fleming (fabaceae) were screened for antimalarial activity to establish validity of their claims. the extracts exhibited antimalarial activity in the 4-day peter's suppressive antimalaria ...	2009	20209008
[mechanisms of liver invasion by malaria sporozoites].		2009	21089536
antimalarial activity of ultra-short peptides.	ultra-short peptides 1-9 were designed and synthesized with phenylalanine, ornithine and proline amino acid residues and their effect on antimalarial activity was analyzed. on the basis of the ic(50) data for these compounds, the effects of nature, polarity, and amino acid sequence on plasmodium berghei schizont cultures were analyzed too. tetrapeptides phe-orn-phe-orn (4) and lys-phe-phe-orn (5) showed a very important activity with ic(50) values of 3.31 and 2.57 microm, respectively. these two ...	2009	20032878
synthesis and evaluation of phenylequine for antimalarial activity in vitro and in vivo.	synthesis of the potent antiplasmodial 4-aminoquinoline, phenylequine (pq), is reported for the first time. pq and the two analogues show increased efficacy in moving from the chloroquine sensitive d10 to the chloroquine resistant k1 strain in vitro. the in vivo efficacy of pq, and salts thereof, have been determined in plasmodium berghei anka and plasmodium yoelii. phenylequine hydrochloride has shown an ed(50) of 0.81 in p. yoelii (cf chloroquine ed(50)=1.31).	2010	20034790
the plasmodium serine-type sera proteases display distinct expression patterns and non-essential in vivo roles during life cycle progression of the malaria parasite.	parasite proteases play key roles in several fundamental steps of the plasmodium life cycle, including haemoglobin degradation, host cell invasion and parasite egress. plasmodium exit from infected host cells appears to be mediated by a class of papain-like cysteine proteases called 'serine repeat antigens' (seras). a sera subfamily, represented by plasmodium falciparum sera5, contains an atypical active site serine residue instead of a catalytic cysteine. members of this seraser subfamily are a ...	2010	20039882
the functional domain of gcs1-based gamete fusion resides in the amino terminus in plant and parasite species.	fertilization is one of the most important processes in all organisms utilizing sexual reproduction. in a previous study, we succeeded in identifying a novel male gametic transmembrane protein gcs1 (generative cell specific 1), also called hap2 (hapless 2) in the male-sterile arabidopsis thaliana mutants, as a factor critical to gamete fusion in flowering plants. interestingly, gcs1 is highly conserved among various eukaryotes covering plants, protists and invertebrates. of these organisms, chla ...	2010	21209845
hemocyte differentiation mediates innate immune memory in anopheles gambiae mosquitoes.	mosquito midgut invasion by ookinetes of the malaria parasite plasmodium disrupts the barriers that normally prevent the gut microbiota from coming in direct contact with epithelial cells. this triggers a long-lived response characterized by increased abundance of granulocytes, a subpopulation of hemocytes that circulates in the insect's hemocoel, and enhanced immunity to bacteria that indirectly reduces survival of plasmodium parasites upon reinfection. in mosquitoes, differentiation of hemocyt ...	2010	20829487
heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of hsp90 from plasmodium falciparum and trypanosoma evansi and evaluation of its inhibitor as a candidate drug.	using a pharmacological inhibitor of hsp90 in cultured malarial parasite, we have previously implicated plasmodium falciparum hsp90 (pfhsp90) as a drug target against malaria. in this study, we have biochemically characterized pfhsp90 in terms of its atpase activity and interaction with its inhibitor geldanamycin (ga) and evaluated its potential as a drug target in a preclinical mouse model of malaria. in addition, we have explored the potential of hsp90 inhibitors as drugs for the treatment of ...	2010	20837488
polar alkaloids from the caribbean marine sponge niphates digitalis.	a method involving flash chromatography, semi-preparative phenylhexyl rp hplc-dad-elsd combined with analytic polar-rp hplc-dad, was applied to separate and purify six highly nitrogenated bases and a bicyclic amidine alkaloid, the major components of the marine sponge niphates digitalis. their structures were identified as 1,8-diazabicyclo[5.4.0]undec-7-ene (1), deoxycytidine (2), phenylalanine (3), adenosine (4), deoxyguanosine (5), adenine (6) and thymidine (7) on the basis of spectroscopic da ...	2010	20839615