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perforin-like protein pplp2 permeabilizes the red blood cell membrane during egress of plasmodium falciparum gametocytes.egress of malaria parasites from the host cell requires the concerted rupture of its enveloping membranes. hence, we investigated the role of the plasmodial perforin-like protein pplp2 in the egress of plasmodium falciparum from erythrocytes. pplp2 is expressed in blood stage schizonts and mature gametocytes. the protein localizes in vesicular structures, which in activated gametocytes discharge pplp2 in a calcium-dependent manner. pplp2 comprises a macpf domain and recombinant pplp2 has haemoly ...201424602217
olyset duo® (a pyriproxyfen and permethrin mixture net): an experimental hut trial against pyrethroid resistant anopheles gambiae and culex quinquefasciatus in southern benin.alternative compounds which can complement pyrethroids on long-lasting insecticidal nets (ln) in the control of pyrethroid resistant malaria vectors are urgently needed. pyriproxyfen (ppf), an insect growth regulator, reduces the fecundity and fertility of adult female mosquitoes. lns containing a mixture of pyriproxyfen and pyrethroid could provide personal protection through the pyrethroid component and reduce vector abundance in the next generation through the sterilizing effect of pyriproxyf ...201424699827
situation of malaria in kolkata municipal corporation area: a secondary data analysis report 2011.a descriptive study was designed based on secondary data of kolkata municipal corporation (kmc).024963229
identification and characterization of the expression profile of micrornas in anopheles anthropophagus.anopheles anthropophagus, one of the most important mosquito-borne disease vectors in asia, mainly takes blood meals from humans and transmits both malaria and filariae. micrornas (mirnas) are small non-coding rnas, and play a critical role in many cellular processes, including development, differentiation, apoptosis and innate immunity.201424690438
cd8+ t cells eliminate liver-stage plasmodium berghei parasites without detectable bystander effect.immunization with attenuated plasmodium sporozoites or viral vectored vaccines can induce protective cd8(+) t cells that can find and eliminate liver-stage malaria parasites. a key question is whether cd8(+) t cells must recognize and eliminate each parasite in the liver or whether bystander killing can occur. to test this, we transferred antigen-specific effector cd8(+) t cells to mice that were then coinfected with two plasmodium berghei strains, only one of which could be recognized directly ...201424421043
criteria for identifying and evaluating candidate sites for open-field trials of genetically engineered mosquitoes.recent laboratory successes in the development of genetically engineered mosquitoes for controlling pathogen transmission have fostered the need for standardized procedures for advancing the technical achievements to practical tools. it is incumbent in many cases for the same scientists doing the in-laboratory discovery research to also take on the initial challenges of developing the pathway that will move the technologies to the field. one of these challenges is having a set of criteria for se ...201424689963
quantitative analysis of plasmodium ookinete motion in three dimensions suggests a critical role for cell shape in the biomechanics of malaria parasite gliding motility.motility is a fundamental part of cellular life and survival, including for plasmodium parasites--single-celled protozoan pathogens responsible for human malaria. the motile life cycle forms achieve motility, called gliding, via the activity of an internal actomyosin motor. although gliding is based on the well-studied system of actin and myosin, its core biomechanics are not completely understood. currently accepted models suggest it results from a specifically organized cellular motor that pro ...201424612056
susceptibility to plasmodium liver stage infection is altered by hepatocyte polyploidy.plasmodium parasites infect hepatocytes of their mammalian hosts and undergo obligate liver stage development. the specific host cell attributes that are important for liver infection remain largely unknown. several host signalling pathways are perturbed in infected hepatocytes, some of which are important in the generation of hepatocyte polyploidy. to test the functional consequence of polyploidy on liver infection, we infected hepatocytes with the rodent malaria parasite plasmodium yoelii both ...201424612025
wolbachia increases susceptibility to plasmodium infection in a natural system.current views about the impact of wolbachia on plasmodium infections are almost entirely based on data regarding artificially transfected mosquitoes. this work has shown that wolbachia reduces the intensity of plasmodium infections in mosquitoes, raising the exciting possibility of using wolbachia to control or limit the spread of malaria. whether natural wolbachia infections have the same parasite-inhibiting properties is not yet clear. wolbachia-mosquito combinations with a long evolutionary h ...201424500167
male aedes aegypti mosquitoes use jh iii transferred during copulation to influence previtellogenic ovary physiology and affect the reproductive output of female mosquitoes.the effect of male accessory gland substances on female reproductive physiology has been previously described as "activating" egg development. however, no mechanism has been described that can explain how male mosquitoes are able to influence egg development in female mosquitoes. to investigate how male mosquitoes are able to influence ovarian physiology and reproductive output we explored three main questions: (1) do mating and male accessory gland substances affect ovarian physiology and alter ...201424657670
characterizing heat shock protein 90 gene of apolygus lucorum (meyer-dür) and its expression in response to different temperature and pesticide stresses.in this study, we cloned a full-length cdna of heat shock protein (hsp) gene of apolygus lucorum (meyer-dür) [alhsp90, kc109781] and investigated its expression in response to temperature and pesticide stresses. the open reading frame (orf) of alhsp90 is 2,169 bp in length, encoding a 722 amino acid polypeptide with a predicted molecular weight of 82.99 kda. transcriptional and translational expression profiles of alhsp90 under extreme temperature or pesticide stresses were examined by fluoresce ...201424623316
phenotypic characterization of plasmodium berghei responsive cd8+ t cells after immunization with live sporozoites under chloroquine cover.an effective malaria vaccine remains elusive. the most effective experimental vaccines confer only limited and short-lived protection despite production of protective antibodies. however, immunization with irradiated sporozoites, or with live sporozoites under chloroquine cover, has resulted in long-term protection apparently due to the generation of protective cd8+ t cells. the nature and function of these protective cd8+ t cells has not been elucidated. in the current study, the phenotype of c ...201424620841
analysis of human b-cell responses following chad63-mva msp1 and ama1 immunization and controlled malaria infection.acquisition of non-sterilizing natural immunity to plasmodium falciparum malaria has been shown in low transmission areas following multiple exposures. however, conflicting data from endemic areas suggest that the parasite may interfere with the induction of effective b-cell responses. to date, the impact of blood-stage parasite exposure on antigen-specific b cells has not been reported following controlled human malaria infection (chmi). here we analysed human b-cell responses in a series of ph ...024303947
five things to know about genetically modified (gm) insects for vector control. 201424603810
fusion of antigen to a dendritic cell targeting chemokine combined with adjuvant yields a malaria dna vaccine with enhanced protective capabilities.although sterilizing immunity to malaria can be elicited by irradiated sporozoite vaccination, no clinically practical subunit vaccine has been shown to be capable of preventing the approximately 600,000 annual deaths attributed to this infection. dna vaccines offer several potential advantages for a disease that primarily affects the developing world, but new approaches are needed to improve the immunogenicity of these vaccines. by using a novel, lipid-based adjuvant, vaxfectin, to attract immu ...201424599116
phosphoinositide metabolism links cgmp-dependent protein kinase g to essential ca²⁺ signals at key decision points in the life cycle of malaria parasites.many critical events in the plasmodium life cycle rely on the controlled release of ca²⁺ from intracellular stores to activate stage-specific ca²⁺-dependent protein kinases. using the motility of plasmodium berghei ookinetes as a signalling paradigm, we show that the cyclic guanosine monophosphate (cgmp)-dependent protein kinase, pkg, maintains the elevated level of cytosolic ca²⁺ required for gliding motility. we find that the same pkg-dependent pathway operates upstream of the ca²⁺ signals tha ...201424594931
efficacy of a plasmodium vivax malaria vaccine using chad63 and modified vaccinia ankara expressing thrombospondin-related anonymous protein as assessed with transgenic plasmodium berghei parasites.plasmodium vivax is the world's most widely distributed malaria parasite and a potential cause of morbidity and mortality for approximately 2.85 billion people living mainly in southeast asia and latin america. despite this dramatic burden, very few vaccines have been assessed in humans. the clinically relevant vectors modified vaccinia virus ankara (mva) and the chimpanzee adenovirus chad63 are promising delivery systems for malaria vaccines due to their safety profiles and proven ability to in ...201324379295
dihydroquinazolinone inhibitors of proliferation of blood and liver stage malaria parasites.drugs that target both the liver and blood stages of malaria will be needed to reduce the disease's substantial worldwide morbidity and mortality. evaluation of a 259-member library of compounds that block proliferation of the blood stage of malaria revealed several scaffolds--dihydroquinazolinones, phenyldiazenylpyridines, piperazinyl methyl quinolones, and bis-benzimidazoles--with promising activity against the liver stage. focused structure-activity studies on the dihydroquinazolinone scaffol ...201324366746
kai407, a potent non-8-aminoquinoline compound that kills plasmodium cynomolgi early dormant liver stage parasites in vitro.preventing relapses of plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. for future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. a new compound with potential radical cure activity was identified using a low-throughput assay of in vitro-cultured hypnozoite forms of plasmodium cynomolgi (an exce ...201324366744
immunization with genetically attenuated p. falciparum parasites induces long-lived antibodies that efficiently block hepatocyte invasion by sporozoites.whole-parasite malaria vaccines have shown promise in clinical trials. we recently reported the first human trial of a malaria vaccine based on plasmodium falciparum genetically attenuated parasites (pfgap). herein we report for the first time that pfgap induces prolonged functional humoral responses in humans. six volunteers were exposed to 5 bites of pfgap-infected mosquitoes followed by approximately 200 bites. plasma collected from all volunteers 3 months after the last exposure efficiently ...201424582635
modulation of anopheles stephensi gene expression by nitroquine, an antimalarial drug against plasmodium yoelii infection in the mosquito.antimalarial drugs may impact mosquito's defense against plasmodium parasites. our previous study showed nitroquine significantly reduced infection of anopheles stephensi by plasmodium yoelii, but the underlying mechanism remains unclear. in order to understand how transmission capacity of an. stephensi was affected by nitroquine, we explored the transcriptome of adult females after different treatments, examined changes in gene expression profiles, and identified transcripts affected by the dru ...201424586804
a cascade of dna-binding proteins for sexual commitment and development in plasmodium.commitment to and completion of sexual development are essential for malaria parasites (protists of the genus plasmodium) to be transmitted through mosquitoes. the molecular mechanism(s) responsible for commitment have been hitherto unknown. here we show that pbap2-g, a conserved member of the apicomplexan ap2 (apiap2) family of dna-binding proteins, is essential for the commitment of asexually replicating forms to sexual development in plasmodium berghei, a malaria parasite of rodents. pbap2-g ...201424572359
the acute transcriptomic and proteomic response of hc-04 hepatoma cells to hepatocyte growth factor and its implications for plasmodium falciparum sporozoite invasion.the routine study of human malaria liver-stage biology in vitro is hampered by low infection efficiency of human hepatocellular carcinoma (hcc) lines (<0.1%), poor understanding of steady-state hcc biology, and lack of appropriate tools for trace sample analysis. hc-04 is the only hcc that supports complete development of human malaria parasites. we hypothesized that hccs are in various intermediate stages of the epithelial-mesenchymal transition (emt) and hc-04s retain epithelial characteristic ...201424532842
transgenic anopheles gambiae expressing an antimalarial peptide suffer no significant fitness cost.mosquito-borne diseases present some of the greatest health challenges faced by the world today. in many cases, existing control measures are compromised by insecticide resistance, pathogen tolerance to drugs and the lack of effective vaccines. in light of these difficulties, new genetic tools for disease control programmes, based on the deployment of genetically modified mosquitoes, are seen as having great promise. transgenic strains may be used to control disease transmission either by suppre ...201424516671
temperature alters plasmodium blocking by wolbachia.very recently, the asian malaria vector (anopheles stephensi) was stably transinfected with the walbb strain of wolbachia, inducing refractoriness to the human malaria parasite plasmodium falciparum. however, conditions in the field can differ substantially from those in the laboratory. we use the rodent malaria p. yoelii, and somatically transinfected an. stephensi as a model system to investigate whether the transmission blocking potential of walbb is likely to be robust across different therm ...201424488176
antibodies to a single, conserved epitope in anopheles apn1 inhibit universal transmission of plasmodium falciparum and plasmodium vivax malaria.malaria transmission-blocking vaccines (tbvs) represent a promising approach for the elimination and eradication of this disease. anapn1 is a lead tbv candidate that targets a surface antigen on the midgut of the obligate vector of the plasmodium parasite, the anopheles mosquito. in this study, we demonstrated that antibodies targeting anapn1 block transmission of plasmodium falciparum and plasmodium vivax across distantly related anopheline species in countries to which malaria is endemic. usin ...201324478095
model for in vivo assessment of humoral protection against malaria sporozoite challenge by passive transfer of monoclonal antibodies and immune serum.evidence from clinical trials of malaria vaccine candidates suggests that both cell-mediated and humoral immunity to pre-erythrocytic parasite stages can provide protection against infection. novel pre-erythrocytic antibody (ab) targets could be key to improving vaccine formulations, which are currently based on targeting antigens such as the circumsporozoite protein (csp). however, methods to assess the effects of sporozoite-specific abs on pre-erythrocytic infection in vivo remain underdevelop ...201324478094
whole pichia pastoris yeast expressing measles virus nucleoprotein as a production and delivery system to multimerize plasmodium antigens.yeasts are largely used as bioreactors for vaccine production. usually, antigens are produced in yeast then purified and mixed with adjuvants before immunization. however, the purification costs and the safety concerns recently raised by the use of new adjuvants argue for alternative strategies. to this end, the use of whole yeast as both production and delivery system appears attractive. here, we evaluated pichia pastoris yeast as an alternative vaccine production and delivery system for the ci ...201424475165
chemical signatures and new drug targets for gametocytocidal drug development.control of parasite transmission is critical for the eradication of malaria. however, most antimalarial drugs are not active against p. falciparum gametocytes, responsible for the spread of malaria. consequently, patients can remain infectious for weeks after the clearance of asexual parasites and clinical symptoms. here we report the identification of 27 potent gametocytocidal compounds (ic50 < 1 μm) from screening 5,215 known drugs and compounds. all these compounds were active against three s ...201424434750
constant diurnal temperature regime alters the impact of simulated climate warming on a tropical pseudoscorpion.recent theory suggests that global warming may be catastrophic for tropical ectotherms. although most studies addressing temperature effects in ectotherms utilize constant temperatures, jensen's inequality and thermal stress considerations predict that this approach will underestimate warming effects on species experiencing daily temperature fluctuations in nature. here, we tested this prediction in a neotropical pseudoscorpion. nymphs were reared in control and high-temperature treatments under ...201424424082
draft genome sequence of asaia sp. strain sf2.1, an important member of the microbiome of anopheles mosquitoes.asaia spp. are abundant members of the microbiota of anopheles mosquitoes, the principle vectors of malaria. here, we report the draft genome sequence of asaia sp. strain sf2.1. this strain is under development as a platform to deliver antimalarial peptides and proteins to adult female anopheles mosquitoes.201424407652
climate and environmental change drives ixodes ricinus geographical expansion at the northern range margin.global environmental change is causing spatial and temporal shifts in the distribution of species and the associated diseases of humans, domesticated animals and wildlife. in the on-going debate on the influence of climate change on vectors and vector-borne diseases, there is a lack of a comprehensive interdisciplinary multi-factorial approach utilizing high quality spatial and temporal data.201424401487
spatial trend, environmental and socioeconomic factors associated with malaria prevalence in chennai.urban malaria is considered to be one of the most significant infectious diseases due to varied socioeconomic problems especially in tropical countries like india. among the south indian cities, chennai is endemic for malaria. the present study aimed to identify the hot spots of malaria prevalence and the relationship with other factors in chennai during 2005-2011.201424400592
simple, sensitive and quantitative bioluminescence assay for determination of malaria pre-patent period.the first phase of malaria infection occurs in the liver and is clinically silent. inside hepatocytes each plasmodium sporozoite replicate into thousands of erythrocyte-infectious merozoites that when released into the blood stream result in clinical symptoms of the disease. the time between sporozoite inoculation and the appearance of parasites in the blood is defined as the pre-patent period, which is classically analysed by time-consuming and labor-intensive techniques, such as microscopy and ...201424400642
enzymes involved in plastid-targeted phosphatidic acid synthesis are essential for plasmodium yoelii liver-stage development.malaria parasites scavenge nutrients from their host but also harbour enzymatic pathways for de novo macromolecule synthesis. one such pathway is apicoplast-targeted type ii fatty acid synthesis, which is essential for late liver-stage development in rodent malaria. it is likely that fatty acids synthesized in the apicoplast are ultimately incorporated into membrane phospholipids necessary for exoerythrocytic merozoite formation. we hypothesized that these synthesized fatty acids are being utili ...201424330260
tafenoquine and npc-1161b require cyp 2d metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds.tafenoquine (tq) is an 8-aminoquinoline (8aq) that has been tested in several phase ii and phase iii clinical studies and is currently in late stage development as an anti-malarial prophylactic agent. npc-1161b is a promising 8aq in late preclinical development. it has recently been reported that the 8aq drug primaquine requires metabolic activation by cyp 2d6 for efficacy in humans and in mice, highlighting the importance of pharmacogenomics in the target population when administering primaquin ...201424386891
hla class ii (dr0401) molecules induce foxp3+ regulatory t cell suppression of b cells in plasmodium yoelii strain 17xnl malaria.unlike human malaria parasites that induce persistent infection, some rodent malaria parasites, like plasmodium yoelii strain 17xnl (py17xnl), induce a transient (self-curing) malaria infection. cooperation between cd4 t cells and b cells to produce antibodies is thought to be critical for clearance of py17xnl parasites from the blood, with major histocompatibility complex (mhc) class ii molecules being required for activation of cd4 t cells. in order to better understand the correspondence betw ...201324166949
host-cell sensors for plasmodium activate innate immunity against liver-stage infection.before they infect red blood cells and cause malaria, plasmodium parasites undergo an obligate and clinically silent expansion phase in the liver that is supposedly undetected by the host. here, we demonstrate the engagement of a type i interferon (ifn) response during plasmodium replication in the liver. we identified plasmodium rna as a previously unrecognized pathogen-associated molecular pattern (pamp) capable of activating a type i ifn response via the cytosolic pattern recognition receptor ...201324362933
malaria situation in an endemic area, southeastern iran.malaria is an endemic infectious disease in southeastern parts of iran. despite years of efforts and intervention programs against malaria, transmission still occurs in jask county.201325629068
evaluation of repellency effect of essential oils of satureja khuzestanica (carvacrol), myrtus communis (myrtle), lavendula officinalis and salvia sclarea using standard who repellency tests.using special lotions and repellent sprays on skin is one of the effective methods to prevent arthropods biting which was verified in this study.201325629066
stress granules and plasmodium liver stage infection.organisms have evolved numerous strategies to control infection by an array of intracellular pathogens. one cell autonomous pathogen control strategy is global inhibition of protein synthesis via stress granule (sg) formation. sgs are induced by stressful stimuli such as oxidative stress and nutrient deprivation, and are known to counteract both viral and bacterial infections. pathogens, in turn, may actively block an infected cell's ability to form sgs. in vitro and in vivo, many liver stage ma ...201424357231
a proteomics and transcriptomics investigation of the venom from the barychelid spider trittame loki (brush-foot trapdoor).although known for their potent venom and ability to prey upon both invertebrate and vertebrate species, the barychelidae spider family has been entirely neglected by toxinologists. in striking contrast, the sister family theraphosidae (commonly known as tarantulas), which last shared a most recent common ancestor with barychelidae over 200 million years ago, has received much attention, accounting for 25% of all the described spider toxins while representing only 2% of all spider species. in th ...201324351713
copper-transporting atpase is important for malaria parasite fertility.homeostasis of the trace element copper is essential to all eukaryotic life. copper serves as a cofactor in metalloenzymes and catalyses electron transfer reactions as well as the generation of potentially toxic reactive oxygen species. here, we describe the functional characterization of an evolutionarily highly conserved, predicted copper-transporting p-type atpase (cutp) in the murine malaria model parasite plasmodium berghei. live imaging of a parasite line expressing a fluorescently tagged ...201324237419
the malarial serine protease sub1 plays an essential role in parasite liver stage development.transmission of the malaria parasite to its vertebrate host involves an obligatory exoerythrocytic stage in which extensive asexual replication of the parasite takes place in infected hepatocytes. the resulting liver schizont undergoes segmentation to produce thousands of daughter merozoites. these are released to initiate the blood stage life cycle, which causes all the pathology associated with the disease. whilst elements of liver stage merozoite biology are similar to those in the much bette ...201324348254
transinfection: a method to investigate wolbachia-host interactions and control arthropod-borne disease.the bacterial endosymbiont wolbachia manipulates arthropod host biology in numerous ways, including sex ratio distortion and differential offspring survival. these bacteria infect a vast array of arthropods, some of which pose serious agricultural and human health threats. wolbachia-mediated phenotypes such as cytoplasmic incompatibility and/or pathogen interference can be used for vector and disease control; however, many medically important vectors and important agricultural species are uninfe ...201324329998
larval nutrition differentially affects adult fitness and plasmodium development in the malaria vectors anopheles gambiae and anopheles stephensi.mosquito fitness is determined largely by body size and nutritional reserves. plasmodium infections in the mosquito and resultant transmission of malaria parasites might be compromised by the vector's nutritional status. we studied the effects of nutritional stress and malaria parasite infections on transmission fitness of anopheles mosquitoes.201324326030
draft genome sequences of elizabethkingia anophelis strains r26t and ag1 from the midgut of the malaria mosquito anopheles gambiae.elizabethkingia anophelis is a species in the family flavobacteriaceae. it is a dominant resident in the mosquito gut and also a human pathogen. we present the draft genome sequences of two strains of e. anophelis, r26(t) and ag1, which were isolated from the midgut of the malaria mosquito anopheles gambiae.201324309745
the relevance and applicability of oocyst prevalence as a read-out for mosquito feeding assays.mosquito feeding assays are important in evaluations of malaria transmission-reducing interventions. the proportion of mosquitoes with midgut oocysts is commonly used as an outcome measure, but in natural low intensity infections the effect of oocyst non-rupture on mosquito infectivity is unclear. by identifying ruptured as well as intact oocysts, we show that in low intensity p. falciparum infections i) 66.7-96.7% of infected mosquitoes experienced oocyst rupture between 11-21 days post-infecti ...201324301557
effect of temperature and humidity on pathogenicity of native beauveria bassiana isolate against musca domestica l.beauveria bassiana hq917687 virulence to housefly larvae and adult was assessed at different relative humidity, rh (50, 75, 90, and 100 %) and temperature (15, 20, 25, 30, 35, 40, 45 °c) conditions at the fungal dose of 10(8) conidia/ml. depending on the temperature and rh regime tested, difference in mortality rates of housefly adult and larvae were detected. during assay on adult housefly, 100 % mortality was achieved at rh, 90 and 100 % while the temperature of 30 °c showed maximum mortality ...201326688637
vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent plasmodium falciparum infection.malaria, which is the result of plasmodium falciparum infection, is a global health threat that resulted in 655,000 deaths and 216 million clinical cases in 2010 alone. recent phase 3 trials with malaria vaccine candidate rts,s/as01 (rts,s) in children has demonstrated modest efficacy against clinical and severe malaria. rts,s targets the pre-erythrocytic phase of the disease and induces high antibody titers against the p. falciparum circumsporozoite protein (csp) and a moderate cd4(+) t cell re ...024292709
male accessory gland substances from aedes albopictus affect the locomotor activity of aedes aegypti females.dengue is one of the world's most important mosquito-borne diseases and is usually transmitted by one of two vector species: aedes aegypti or aedes albopictus . these two diurnal mosquitoes are frequently found coexisting in similar habitats, enabling interactions between adults, such as cross-mating. the objective of this study was to assess cross-mating between ae. aegypti females and ae. albopictus males under artificial conditions and evaluate the locomotor activity of ae. aegypti virgin fem ...024473799
infravec: research capacity for the implementation of genetic control of mosquitoes.mosquitoes represent a major and global cause of human suffering due to the diseases they transmit. these include parasitic diseases, i.e. malaria and filariasis, and viral infections such as dengue, encephalitis, and yellow fever. the threat of mosquito-borne diseases is not limited to tropical and subtropical regions of the world. trade and climate changes have opened new niches to tropical vectors in temperate areas of the world, thus putting previously unaffected regions at risk of disease t ...024428829
functional comparison of plasmodium falciparum transmission-blocking vaccine candidates by the standard membrane-feeding assay.recently, there has been a renewed interest in the development of transmission-blocking vaccines (tbv) against plasmodium falciparum malaria. while several candidate tbvs have been reported, studies directly comparing them in functional assays are limited. to this end, recombinant proteins of tbv candidates pfs25, pfs230, and pfhap2 were expressed in the wheat germ cell-free expression system. outbred cd-1 mice were immunized twice with the antigens. two weeks after the second immunization, igg ...201324042109
hypoxia promotes liver-stage malaria infection in primary human hepatocytes in vitro.homeostasis of mammalian cell function strictly depends on balancing oxygen exposure to maintain energy metabolism without producing excessive reactive oxygen species. in vivo, cells in different tissues are exposed to a wide range of oxygen concentrations, and yet in vitro models almost exclusively expose cultured cells to higher, atmospheric oxygen levels. existing models of liver-stage malaria that utilize primary human hepatocytes typically exhibit low in vitro infection efficiencies, possib ...201324291761
protective cd8+ t-cell immunity to human malaria induced by chimpanzee adenovirus-mva immunisation.induction of antigen-specific cd8(+) t cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced cd8(+) t cells that correlate with efficacy in humans. here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus ankara booster induces exceptionally high frequency t-cell responses (median >2400 sfc/10(6) peripheral blood mononuclear cells) to the liver-stage plasmodium falciparum malaria a ...024284865
targeting plasmodium pi(4)k to eliminate malaria.achieving the goal of malaria elimination will depend on targeting plasmodium pathways essential across all life stages. here we identify a lipid kinase, phosphatidylinositol-4-oh kinase (pi(4)k), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple plasmodium species at each stage of infection in the vertebrate host. imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent ma ...201324284631
inhibitor of cysteine proteases is critical for motility and infectivity of plasmodium sporozoites.malaria is transmitted when motile sporozoites are injected into the dermis by an infected female anopheles mosquito. inside the mosquito vector, sporozoites egress from midgut-associated oocysts and eventually penetrate the acinar cells of salivary glands. parasite-encoded factors with exclusive vital roles in the insect vector can be studied by classical reverse genetics. here, we characterized the in vivo roles of plasmodium berghei falstatin/icp (inhibitor of cysteine proteases). this protei ...201324281719
molecular detection and quantification of plasmodium falciparum-infected human hepatocytes in chimeric immune-deficient mice.chimeric mice with humanized livers represent a promising tool for infections with plasmodium falciparum to evaluate novel methods for prevention and treatment of pre-erythrocytic stages. adequate assessment of hepatic infections is generally compromised by the limited number of human hepatocytes infected by developing parasites.201324267791
killer bee molecules: antimicrobial peptides as effector molecules to target sporogonic stages of plasmodium.a new generation of strategies is evolving that aim to block malaria transmission by employing genetically modified vectors or mosquito pathogens or symbionts that express anti-parasite molecules. whilst transgenic technologies have advanced rapidly, there is still a paucity of effector molecules with potent anti-malaria activity whose expression does not cause detrimental effects on mosquito fitness. our objective was to examine a wide range of antimicrobial peptides (amps) for their toxic effe ...201324278025
a small molecule glycosaminoglycan mimetic blocks plasmodium invasion of the mosquito midgut.malaria transmission-blocking (t-b) interventions are essential for malaria elimination. small molecules that inhibit the plasmodium ookinete-to-oocyst transition in the midgut of anopheles mosquitoes, thereby blocking sporogony, represent one approach to achieving this goal. chondroitin sulfate glycosaminoglycans (cs-gags) on the anopheles gambiae midgut surface are putative ligands for plasmodium falciparum ookinetes. we hypothesized that our synthetic polysulfonated polymer, vs1, acting as a ...201324278017
a plant-produced pfs25 vlp malaria vaccine candidate induces persistent transmission blocking antibodies against plasmodium falciparum in immunized mice.malaria transmission blocking vaccines (tbvs) are considered an effective means to control and eventually eliminate malaria. the pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for tbv. it has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (vlps). we engineered ...201324260245
positive selection drives accelerated evolution of mosquito salivary genes associated with blood-feeding.the saliva of bloodsucking animals contains dozens to hundreds of proteins that counteract their hosts' haemostasis, inflammation and immunity. it was previously observed that salivary proteins involved in haematophagy are much more divergent in their primary sequence than those of housekeeping function, when comparisons were made between closely related organisms. while this pattern of evolution could result from relaxed selection or drift, it could alternatively be the result of positive selec ...201324237399
plasmodium berghei calcium dependent protein kinase 1 is not required for host cell invasion.plasmodium calcium dependent protein kinase (cdpk1) is required for the development of sexual stages in the mosquito. in addition, it is proposed to play an essential role in the parasite's invasive stages possibly through the regulation of the actinomyosin motor and micronemal secretion. we demonstrate that plasmodium berghei cdpk1 is dispensable in the parasite's erythrocytic and pre-erythrocytic stages. we successfully disrupted p. berghei cdpk1 (pbcdpk1) by homologous recombination. the reco ...201324265753
trem2 governs kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection.plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (trem2) and mhc class ii molecules as determinants of plasmodium berghei liver stage infection in mice. locus belr1 confers resistance to malaria liver stage infection. the use of newly derived subcongenic mouse lines allo ...201324218563
complex environmental drivers of immunity and resistance in malaria mosquitoes.considerable research effort has been directed at understanding the genetic and molecular basis of mosquito innate immune mechanisms. whether environmental factors interact with these mechanisms to shape overall resistance remains largely unexplored. here, we examine how changes in mean ambient temperature, diurnal temperature fluctuation and time of day of infection affected the immunity and resistance of anopheles stephensi to infection with escherichia coli. we used quantitative pcr to estima ...201324048159
human immune responses to plasmodium falciparum infection: molecular evidence for a suboptimal thαβ and th17 bias over ideal and effective traditional th1 immune response.using microarray analysis, this study showed up-regulation of toll-like receptors 1, 2, 4, 7, 8, nf-κb, tnf, p38-mapk, and mhc molecules in human peripheral blood mononuclear cells following infection with plasmodium falciparum.201324188121
towards an optimized inhibition of liver stage development assay (ilsda) for plasmodium falciparum.experimental vaccines targeting plasmodium falciparum have had some success in recent years. these vaccines use attenuated parasites, recombinant sporozoite proteins, or dna and virus combinations to induce cell-mediated immune responses and/or antibodies targeting sporozoite surface proteins. to capitalize on the success of these vaccines and understand the mechanisms by which these vaccines function, it is important to develop assays that measure correlates of protection in volunteers. the inh ...201324191920
crimalddi: platform technologies and novel anti-malarial drug targets.the coordination, rationalization, and integration of antimalarial drug discovery & development initiatives (crimalddi) consortium, funded by the eu framework seven programme, has attempted, through a series of interactive and facilitated workshops, to develop priorities for research to expedite the discovery of new anti-malarials. this paper outlines the recommendations for the development of enabling technologies and the identification of novel targets.screening systems must be robust, validat ...201324498961
overexpression of multiple detoxification genes in deltamethrin resistant laodelphax striatellus (hemiptera: delphacidae) in china.the small brown planthopper (sbph), laodelphax striatellus (fallén), is one of the major rice pests in asia and has developed resistance to multiple classes of insecticides. understanding resistance mechanisms is essential to the management of this pest. biochemical and molecular assays were performed in this study to systematically characterize deltamethrin resistance mechanisms with laboratory-selected resistant and susceptible strains of sbph.201324324548
short-lived effector cd8 t cells induced by genetically attenuated malaria parasite vaccination express cd11c.vaccination with a single dose of genetically attenuated malaria parasites can induce sterile protection against sporozoite challenge in the rodent plasmodium yoelii model. protection is dependent on cd8(+) t cells, involves perforin and gamma interferon (ifn-γ), and is correlated with the expansion of effector memory cd8(+) t cells in the liver. here, we have further characterized vaccine-induced changes in the cd8(+) t cell phenotype and demonstrated significant upregulation of cd11c on cd3(+) ...201323980113
kinetic flux profiling elucidates two independent acetyl-coa biosynthetic pathways in plasmodium falciparum.the malaria parasite plasmodium falciparum depends on glucose to meet its energy requirements during blood-stage development. although glycolysis is one of the best understood pathways in the parasite, it is unclear if glucose metabolism appreciably contributes to the acetyl-coa pools required for tricarboxylic acid metabolism (tca) cycle and fatty acid biosynthesis. p. falciparum possesses a pyruvate dehydrogenase (pdh) complex that is localized to the apicoplast, a specialized quadruple membra ...201324163372
assessment of dual life stage antiplasmodial activity of british seaweeds.terrestrial plants have proven to be a prolific producer of clinically effective antimalarial drugs, but the antimalarial potential of seaweeds has been little explored. the main aim of this study was to assess the in vitro chemotherapeutical and prophylactic potential of the extracts of twenty-three seaweeds collected from the south coast of england against blood stage (bs) and liver stage (ls) plasmodium parasites. the majority (14) of the extracts were active against bs of p. falciparum, with ...201324152562
plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission.efficient transmission of plasmodium species between humans and anopheles mosquitoes is a major contributor to the global burden of malaria. gametocytogenesis, the process by which parasites switch from asexual replication within human erythrocytes to produce male and female gametocytes, is a critical step in malaria transmission and plasmodium genetic diversity. nothing is known about the pathways that regulate gametocytogenesis and only few of the current drugs that inhibit asexual replication ...201324145416
pharmacological and phytochemical appraisal of selected medicinal plants from jordan with claimed antidiabetic activities.plant species have long been regarded as possessing the principal ingredients used in widely disseminated ethnomedical practices. different surveys showed that medicinal plant species used by the inhabitants of jordan for the traditional treatment of diabetes are inadequately screened for their therapeutic/preventive potential and phytochemical findings. in this review, traditional herbal medicine pursued indigenously with its methods of preparation and its active constituents are listed. studie ...201324482764
evaluation of the long-lasting insecticidal net interceptor ln: laboratory and experimental hut studies against anopheline and culicine mosquitoes in northeastern tanzania.long lasting insecticidal nets (ln) are a primary method of malaria prevention. before new types of ln are approved they need to meet quality and efficacy standards set by the who pesticide evaluation scheme. the process of evaluation has three phases. in phase i the candidate ln must meet threshold bioassay criteria after 20 standardized washes. in phase ii washed and unwashed lns are evaluated in experimental huts against wild, free flying anopheline mosquitoes. in phase iii the ln are distrib ...201324499488
protein kinase c-dependent signaling controls the midgut epithelial barrier to malaria parasite infection in anopheline mosquitoes.anopheline mosquitoes are the primary vectors of parasites in the genus plasmodium, the causative agents of malaria. malaria parasites undergo a series of complex transformations upon ingestion by the mosquito host. during this process, the physical barrier of the midgut epithelium, along with innate immune defenses, functionally restrict parasite development. although these defenses have been studied for some time, the regulatory factors that control them are poorly understood. the protein kina ...201324146884
a specific inhibitor of pfcdpk4 blocks malaria transmission: chemical-genetic validation.malaria parasites are transmitted by mosquitoes, and blocking parasite transmission is critical in reducing or eliminating malaria in endemic regions. here, we report the pharmacological characterization of a new class of malaria transmission-blocking compounds that acts via the inhibition of plasmodia cdpk4 enzyme. we demonstrate that these compounds achieved selectivity over mammalian kinases by capitalizing on a small serine gatekeeper residue in the active site of the plasmodium cdpk4 enzyme ...201324123773
apical membrane antigen 1 mediates apicomplexan parasite attachment but is dispensable for host cell invasion.apicomplexan parasites invade host cells by forming a ring-like junction with the cell surface and actively sliding through the junction inside an intracellular vacuole. apical membrane antigen 1 is conserved in apicomplexans and a long-standing malaria vaccine candidate. it is considered to have multiple important roles during host cell penetration, primarily in structuring the junction by interacting with the rhoptry neck 2 protein and transducing the force generated by the parasite motor duri ...024108241
impact of trehalose transporter knockdown on anopheles gambiae stress adaptation and susceptibility to plasmodium falciparum infection.anopheles gambiae is a major vector mosquito for plasmodium falciparum, the deadly pathogen causing most human malaria in sub-saharan africa. synthesized in the fat body, trehalose is the predominant sugar in mosquito hemolymph. it not only provides energy but also protects the mosquito against desiccation and heat stresses. trehalose enters the mosquito hemolymph by the trehalose transporter agtret1. in adult female a. gambiae, agtret1 is predominantly expressed in the fat body. we found that a ...201324101462
chemicals, climate, and control: increasing the effectiveness of malaria vector control tools by considering relevant temperatures. 201324098111
a key role for plasmodium subtilisin-like sub1 protease in egress of malaria parasites from host hepatocytes.in their mammalian host, plasmodium parasites have two obligatory intracellular development phases, first in hepatocytes and subsequently in erythrocytes. both involve an orchestrated process of invasion into and egress from host cells. the plasmodium sub1 protease plays a dual role at the blood stage by enabling egress of the progeny merozoites from the infected erythrocyte and priming merozoites for subsequent erythrocyte invasion. here, using conditional mutagenesis in p. berghei, we show tha ...201324089525
therapeutic uses and pharmacological properties of garlic, shallot, and their biologically active compounds.garlic (allium sativum l. family liliaceae) is well known in iran and its leaves, flowers, and cloves have been used in traditional medicine for a long time. research in recent decades has shown widespread pharmacological effects of a. sativum and its organosulfur compounds especially allicin. studies carried out on the chemical composition of the plant show that the most important constituents of this plant are organosulfur compounds such as allicin, diallyl disulphide, s-allylcysteine, and dia ...024379960
cd8+ t cells specific for a malaria cytoplasmic antigen form clusters around infected hepatocytes and are protective at the liver stage of infection.following anopheles mosquito-mediated introduction into a human host, plasmodium parasites infect hepatocytes and undergo intensive replication. accumulating evidence indicates that cd8(+) t cells induced by immunization with attenuated plasmodium sporozoites can confer sterile immunity at the liver stage of infection; however, the mechanisms underlying this protection are not clearly understood. to address this, we generated recombinant plasmodium berghei anka expressing a fusion protein of an ...201323897612
plasmodium dipeptidyl aminopeptidases as malaria transmission-blocking drug targets.the plasmodium falciparum and p. berghei genomes each contain three dipeptidyl aminopeptidase (dpap) homologs. dpap1 and -3 are critical for asexual growth, but the role of dpap2, the gametocyte-specific homolog, has not been tested. if dpaps are essential for transmission as well as asexual growth, then a dpap inhibitor could be used for treatment and to block transmission. to directly analyze the role of dpap2, a dpap2-minus p. berghei (pbdpap2δ) line was generated. the pbdpap2δ parasites grew ...201323836185
bioefficacy of crude extract of cyperus aromaticus (family: cyperaceae) cultured cells, against aedes aegypti and aedes albopictus mosquitoes.to evaluate the growth inhibition activity of the crude extract of cyperus aromaticus (c. aromaticus) cultured cells against the 3rd instar larvae of aedes aegypti (linn.) and aedes albopictus skuse (ae. albopictus) under laboratory conditions, and determine the sublethal effects (ei50) of the crude extract of c. aromaticus cultured cells on some biological and morphological parameters of both aedes mosquito species during two generations as well.201324075340
blocking malaria transmission to anopheles mosquitoes using artemisinin derivatives and primaquine: a systematic review and meta-analysis.among the currently used drugs in malaria case management, artemisinin derivatives and primaquine have an impact on the transmissible stages of plasmodium falciparum. hence, they reduce the transmission of the parasite from the patient to the mosquitoes. the present study aimed to assess evidence for this hypothesis from controlled trials.201324499628
comparative susceptibility of different biological forms of anopheles stephensi to plasmodium berghei anka strain.there are varying degrees of compatibility between malaria parasite-mosquito species, and understanding this compatibility may be crucial for developing effective transmission-blocking vaccines. this study investigates the compatibility of different biological forms of a malaria vector, anopheles stephensi, to plasmodium berghei anka strain.201324086525
unique apicomplexan imc sub-compartment proteins are early markers for apical polarity in the malaria parasite.the phylum apicomplexa comprises over 5000 intracellular protozoan parasites, including plasmodium and toxoplasma, that are clinically important pathogens affecting humans and livestock. malaria parasites belonging to the genus plasmodium possess a pellicle comprised of a plasmalemma and inner membrane complex (imc), which is implicated in parasite motility and invasion. using live cell imaging and reverse genetics in the rodent malaria model p. berghei, we localise two unique imc sub-compartmen ...201324244852
effects of drying eggs and egg storage on hatchability and development of anopheles arabiensis.the mass rearing of insects requires a large colony from which individuals can be harvested for sterilization and release. attention is given to larval food requirements and to handling and rearing conditions to ensure predictability and synchrony of development. maximizing production requires optimized adult holding to ensure mating success, blood feeding and oviposition. appropriate egg storage and harvesting is necessary to compensate any unpredicted reduction in egg production.201324028497
asaia accelerates larval development of anopheles gambiae.arthropod borne diseases cause significant human morbidity and mortality and, therefore, efficient measures to control transmission of the disease agents would have great impact on human health. one strategy to achieve this goal is based on the manipulation of bacterial symbionts of vectors. bacteria of the gram-negative, acetic acid bacterium genus asaia have been found to be stably associated with larvae and adults of the southeast asian malaria vector anopheles stephensi, dominating the micro ...201324091152
development of the bg-malaria trap as an alternative to human-landing catches for the capture of anopheles darlingi.although the human-landing catch (hlc) method is the most effective for collecting anthropophilic anophelines, it has been increasingly abandoned, primarily for ethical considerations. the objective of the present study was to develop a new trap for the collection of anopheles darlingi . the initial trials were conducted using the bg-sentinel trap as a standard for further trap development based on colour, airflow direction and illumination. the performance of the trap was then compared with tho ...024037199
mosquito larval source management for controlling malaria.malaria is an important cause of illness and death in people living in many parts of the world, especially sub-saharan africa. long-lasting insecticide treated bed nets (llins) and indoor residual spraying (irs) reduce malaria transmission by targeting the adult mosquito vector and are key components of malaria control programmes. however, mosquito numbers may also be reduced by larval source management (lsm), which targets mosquito larvae as they mature in aquatic habitats. this is conducted by ...201323986463
expression profiling of plasmodium berghei hsp70 genes for generation of bright red fluorescent parasites.live cell imaging of recombinant malarial parasites encoding fluorescent probes provides critical insights into parasite-host interactions and life cycle progression. in this study, we generated a red fluorescent line of the murine malarial parasite plasmodium berghei. to allow constitutive and abundant expression of the mcherry protein we profiled expression of all members of the p. berghei heat shock protein 70 (hsp70) family. we identified pbhsp70/1, an invariant ortholog of plasmodium falcip ...201324013507
in vivo cd8+ t cell dynamics in the liver of plasmodium yoelii immunized and infected mice.plasmodium falciparum malaria remains one of the most serious health problems globally and a protective malaria vaccine is desperately needed. vaccination with attenuated parasites elicits multiple cellular effector mechanisms that lead to plasmodium liver stage elimination. while granule-mediated cytotoxicity requires contact between cd8+ effector t cells and infected hepatocytes, cytokine secretion should allow parasite killing over longer distances. to better understand the mechanism of paras ...201323967119
protective efficacy of baculovirus dual expression system vaccine expressing plasmodium falciparum circumsporozoite protein.we have previously developed a new malaria vaccine delivery system based on the baculovirus dual expression system (bdes). in this system, expression of malaria antigens is driven by a dual promoter consisting of the baculovirus-derived polyhedrin and mammal-derived cytomegalovirus promoters. to test this system for its potential as a vaccine against human malaria parasites, we investigated immune responses against the newly developed bdes-based plasmodium falciparum circumsporozoite protein vac ...201323951015
malaria parasite liver stages render host hepatocytes susceptible to mitochondria-initiated apoptosis.intracellular eukaryotic parasites and their host cells constitute complex, coevolved cellular interaction systems that frequently cause disease. among them, plasmodium parasites cause a significant health burden in humans, killing up to one million people annually. to succeed in the mammalian host after transmission by mosquitoes, plasmodium parasites must complete intracellular replication within hepatocytes and then release new infectious forms into the blood. using plasmodium yoelii rodent m ...201323928701
development of a chimeric plasmodium berghei strain expressing the repeat region of the p. vivax circumsporozoite protein for in vivo evaluation of vaccine efficacy.the development of vaccine candidates against plasmodium vivax-the most geographically widespread human malaria species-is challenged by technical difficulties, such as the lack of in vitro culture systems and availability of animal models. chimeric rodent plasmodium parasites are safe and useful tools for the preclinical evaluation of new vaccine formulations. we report the successful development and characterization of chimeric plasmodium berghei parasites bearing the type i repeat region of p ...201323716612
'manipulation' without the parasite: altered feeding behaviour of mosquitoes is not dependent on infection with malaria parasites.previous studies have suggested that plasmodium parasites can manipulate mosquito feeding behaviours such as probing, persistence and engorgement rate in order to enhance transmission success. here, we broaden analysis of this 'manipulation phenotype' to consider proximate foraging behaviours, including responsiveness to host odours and host location. using anopheles stephensi and plasmodium yoelii as a model system, we demonstrate that mosquitoes with early stage infections (i.e. non-infectious ...201323698008
insulin signaling and the regulation of insect diapause.a rich chapter in the history of insect endocrinology has focused on hormonal control of diapause, especially the major roles played by juvenile hormones (jhs), ecdysteroids, and the neuropeptides that govern jh and ecdysteroid synthesis. more recently, experiments with adult diapause in drosophila melanogaster and the mosquito culex pipiens, and pupal diapause in the flesh fly sarcophaga crassipalpis provide strong evidence that insulin signaling is also an important component of the regulatory ...201323885240
comparison of metabolic capacities and inference of gene content evolution in mosquito-associated spiroplasma diminutum and s. taiwanense.mosquitoes are hosts of several spiroplasma species that belong to different serogroups. to investigate the genetic mechanisms that may be involved in the utilization of similar hosts in these phylogenetically distinct bacteria, we determined the complete genome sequences of spiroplasma diminutum and s. taiwanense for comparative analysis. the genome alignment indicates that their chromosomal organization is highly conserved, which is in sharp contrast to the elevated genome instabilities observ ...023873917
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