Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| suppressor of hairy-wing, modifier of mdg4 and centrosomal protein of 190 gene orthologues of the gypsy insulator complex in the malaria mosquito, anopheles stephensi. | dna insulators organize independent gene regulatory domains and can regulate interactions amongst promoter and enhancer elements. they have the potential to be important in genome enhancing and editing technologies because they can mitigate chromosomal position effects on transgenes. the orthologous genes of the anopheles stephensi putative gypsy-like insulator protein complex were identified and expression characteristics studied. these genes encode polypeptides with all the expected protein do ... | 2016 | 27110891 |
| a plasmodium yoelii mei2-like rna binding protein is essential for completion of liver stage schizogony. | plasmodium parasites employ posttranscriptional regulatory mechanisms as their life cycle transitions between host cell invasion and replication within both the mosquito vector and mammalian host. rna binding proteins (rbps) provide one mechanism for modulation of rna function. to explore the role of plasmodium rbps during parasite replication, we searched for rbps that might play a role during liver stage development, the parasite stage that exhibits the most extensive growth and replication. w ... | 2016 | 26883588 |
| an ultrasensitive nanoluc-based luminescence system for monitoring plasmodium berghei throughout its life cycle. | bioluminescence imaging is widely used for cell-based assays and animal imaging studies, both in biomedical research and drug development. its main advantages include its high-throughput applicability, affordability, high sensitivity, operational simplicity, and quantitative outputs. in malaria research, bioluminescence has been used for drug discovery in vivo and in vitro, exploring host-pathogen interactions, and studying multiple aspects of plasmodium biology. while the number of fluorescent ... | 2016 | 27102897 |
| enhanced transmission of malaria parasites to mosquitoes in a murine model of type 2 diabetes. | more than half of the world's population is at risk of malaria and simultaneously, many malaria-endemic regions are facing dramatic increases in the prevalence of type 2 diabetes. studies in murine malaria models have examined the impact of malaria infection on type 2 diabetes pathology, it remains unclear how this chronic metabolic disorder impacts the transmission of malaria. in this report, the ability type 2 diabetic rodents infected with malaria to transmit parasites to anopheles stephensi ... | 2016 | 27102766 |
| a novel xenomonitoring technique using mosquito excreta/feces for the detection of filarial parasites and malaria. | given the continued successes of the world's lymphatic filariasis (lf) elimination programs and the growing successes of many malaria elimination efforts, the necessity of low cost tools and methodologies applicable to long-term disease surveillance is greater than ever before. as many countries reach the end of their lf mass drug administration programs and a growing number of countries realize unprecedented successes in their malaria intervention efforts, the need for practical molecular xenom ... | 2016 | 27096156 |
| the plasmodium alveolin imc1a is stabilised by its terminal cysteine motifs and facilitates sporozoite morphogenesis and infectivity in a dose-dependent manner. | apicomplexan parasites possess a unique cortical cytoskeleton structure composed of intermediate filaments. its building blocks are provided by a conserved family of proteins named alveolins. the core alveolin structure is made up of tandem repeat sequences, thought to be responsible for the filamentous properties of these proteins. a subset of alveolins also possess conserved motifs composed of three closely spaced cysteine residues situated near the ends of the polypeptides. the roles of these ... | 2016 | 27693349 |
| epidemiology of plasmodium vivax in indonesia. | endemic malaria occurs across much of the vast indonesian archipelago. all five species of plasmodium known to naturally infect humans occur here, along with 20 species of anopheles mosquitoes confirmed as carriers of malaria. two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in indonesia: plasmodium falciparum and plasmodium vivax the challenge posed by p. vivax is especially steep in indonesia because chloroquine-resistant strains predomi ... | 2016 | 27708185 |
| global epidemiology of plasmodium vivax. | plasmodium vivax is the most widespread human malaria, putting 2.5 billion people at risk of infection. its unique biological and epidemiological characteristics pose challenges to control strategies that have been principally targeted against plasmodium falciparum unlike p. falciparum, p. vivax infections have typically low blood-stage parasitemia with gametocytes emerging before illness manifests, and dormant liver stages causing relapses. these traits affect both its geographic distribution a ... | 2016 | 27402513 |
| antimicrobial dependence of silver nanoparticles on surface plasmon resonance bands against escherichia coli. | this study presents a simple and trouble-free method for determining the antimicrobial properties of silver nanoparticles (agnps) based on the surface plasmon resonance (spr) bands. agnps were prepared by chemical reduction method using silver nitrates as a metallic precursor and formaldehyde (hcho) as a reducing agent and capped by polyethylene glycol. effects of several processing variables on the size and shape of agnps were monitored using an ultraviolet-visible spectrophotometer based on th ... | 2016 | 28053512 |
| a novel fikk kinase regulates the development of mosquito and liver stages of the malaria. | protein phosphorylation is the most important post-translational event in the regulation of various essential signaling pathways in a cell. here, we show the functional characterization of a fikk family protein kinase of the rodent malaria parasite (pbmlfk), which is expressed only in mosquito and liver stages and contains two functional c-terminal pexel motifs. we demonstrate that this protein plays a role in mosquito and liver stages of parasite growth. the oocysts of pbmlfk-deficient parasite ... | 2016 | 27995998 |
| molecular analysis of pfs47-mediated plasmodium evasion of mosquito immunity. | malaria is a life-threatening disease caused by plasmodium falciparum parasites that is transmitted through the bites of infected anopheline mosquitoes. p. falciparum dispersal from africa, as a result of human migration, required adaptation of the parasite to several different indigenous anopheline species. the mosquito immune system can greatly limit infection and p. falciparum evolved a strategy to evade these responses that is mediated by the pfs47 gene. pfs47 is a polymorphic gene with sign ... | 2016 | 27992481 |
| nonobese diabetic (nod) mice lack a protective b-cell response against the "nonlethal" plasmodium yoelii 17xnl malaria protozoan. | background. plasmodium yoelii 17xnl is a nonlethal malaria strain in mice of different genetic backgrounds including the c57bl/6 mice (i-a(b)/i-e(null)) used in this study as a control strain. we have compared the trends of blood stage infection with the nonlethal murine strain of p. yoelii 17xnl malaria protozoan in immunocompetent nonobese diabetic (nod) mice prone to type 1 diabetes (t1d) and c57bl/6 mice (control mice) that are not prone to t1d and self-cure the p. yoelii 17xnl infection. pr ... | 2016 | 28074170 |
| safety and reproducibility of a clinical trial system using induced blood stage plasmodium vivax infection and its potential as a model to evaluate malaria transmission. | interventions to interrupt transmission of malaria from humans to mosquitoes represent an appealing approach to assist malaria elimination. a limitation has been the lack of systems to test the efficacy of such interventions before proceeding to efficacy trials in the field. we have previously demonstrated the feasibility of induced blood stage malaria (ibsm) infection with plasmodium vivax. in this study, we report further validation of the ibsm model, and its evaluation for assessment of trans ... | 2016 | 27930652 |
| corrigendum. | 2016 | 27927971 | |
| cytochrome p450 2d-mediated metabolism is not necessary for tafenoquine and primaquine to eradicate the erythrocytic stages of plasmodium berghei. | due to the ability of the 8-aminoquinolines (8aqs) to kill different stages of the malaria parasite, primaquine (pq) and tafenoquine (tq) are vital for causal prophylaxis and the eradication of erythrocytic plasmodium sp. parasites. recognizing the potential role of cytochrome (cyp) 450 2d6 in the metabolism and subsequent hepatic efficacy of 8-aminoquinolines, studies were designed to explore whether cyp2d-mediated metabolism was related to the ability of single-dose pq and tq to eliminate the ... | 2016 | 27923405 |
| plasmodium yoelii nigeriensis (n67) is a robust animal model to study malaria transmission by south american anopheline mosquitoes. | malaria is endemic in the american continent and the amazonian rainforest is the region with the highest risk of transmission. however, the lack of suitable experimental models to infect malaria vectors from the americas has limited the progress to understand the biology of transmission in this region. anopheles aquasalis, a major vector in coastal areas of south america, was found to be highly refractory to infection with two strains of plasmodium falciparum (nf54 and 7g8) and with plasmodium b ... | 2016 | 27911924 |
| population density, climate variables and poverty synergistically structure spatial risk in urban malaria in india. | the world is rapidly becoming urban with the global population living in cities projected to double by 2050. this increase in urbanization poses new challenges for the spread and control of communicable diseases such as malaria. in particular, urban environments create highly heterogeneous socio-economic and environmental conditions that can affect the transmission of vector-borne diseases dependent on human water storage and waste water management. interestingly india, as opposed to africa, har ... | 2016 | 27906962 |
| demographic and clinical profiles of plasmodium falciparum and plasmodium vivax patients at a tertiary care centre in southwestern india. | malaria remains an important cause of morbidity and mortality in india. though many comprehensive studies have been carried out in africa and southeast asia to characterize and examine determinants of plasmodium falciparum and plasmodium vivax malaria pathogenesis, fewer have been conducted in india. | 2016 | 27884146 |
| methanolic extract of agerantum conyzoides exhibited toxicity and growth disruption activities against anopheles gambiae sensu stricto and anopheles arabiensis larvae. | vector control remains the mainstay to effective malaria management. the negative implications following persistent application of synthetic insecticides geared towards regulation of mosquito populations have necessitated prospection for ecofriendly effective chemistries. plant-derived compounds have the potential to control malaria-transmitting mosquito populations. previously, agerantum conyzoides extracts have demonstrated toxicity effects on disease-transmitting mosquitoes. however, their ef ... | 2016 | 27876055 |
| identification of genes for engineering the male germline of aedes aegypti and ceratitis capitata. | synthetic biology approaches are promising new strategies for control of pest insects that transmit disease and cause agricultural damage. these strategies require characterised modular components that can direct appropriate expression of effector sequences, with components conserved across species being particularly useful. the goal of this study was to identify genes from which new potential components could be derived for manipulation of the male germline in two major pest species, the mosqui ... | 2016 | 27871244 |
| variant exported blood-stage proteins encoded by plasmodium multigene families are expressed in liver stages where they are exported into the parasitophorous vacuole. | many variant proteins encoded by plasmodium-specific multigene families are exported into red blood cells (rbc). p. falciparum-specific variant proteins encoded by the var, stevor and rifin multigene families are exported onto the surface of infected red blood cells (irbc) and mediate interactions between irbc and host cells resulting in tissue sequestration and rosetting. however, the precise function of most other plasmodium multigene families encoding exported proteins is unknown. to understa ... | 2016 | 27851824 |
| a putative small solute transporter is responsible for the secretion of g377 and trap-containing secretory vesicles during plasmodium gamete egress and sporozoite motility. | regulated protein secretion is required for malaria parasite life cycle progression and transmission between the mammalian host and mosquito vector. during transmission from the host to the vector, exocytosis of highly specialised secretory vesicles, such as osmiophilic bodies, is key to the dissolution of the red blood cell and parasitophorous vacuole membranes enabling gamete egress. the positioning of adhesins from the trap family, from micronemes to the sporozoite surface, is essential for g ... | 2016 | 27427910 |
| comparative plasmodium gene overexpression reveals distinct perturbation of sporozoite transmission by profilin. | plasmodium relies on actin-based motility to migrate from the site of infection and invade target cells. using a substrate-dependent gliding locomotion, sporozoites are able to move at fast speed (1-3 μm/s). this motility relies on a minimal set of actin regulatory proteins and occurs in the absence of detectable filamentous actin (f-actin). here we report an overexpression strategy to investigate whether perturbations of f-actin steady-state levels affect gliding locomotion and host invasion. w ... | 2016 | 27226484 |
| the actin filament-binding protein coronin regulates motility in plasmodium sporozoites. | parasites causing malaria need to migrate in order to penetrate tissue barriers and enter host cells. here we show that the actin filament-binding protein coronin regulates gliding motility in plasmodium berghei sporozoites, the highly motile forms of a rodent malaria-causing parasite transmitted by mosquitoes. parasites lacking coronin show motility defects that impair colonization of the mosquito salivary glands but not migration in the skin, yet result in decreased transmission efficiency. in ... | 2016 | 27409081 |
| mosquitocidal effect of glycosmis pentaphylla leaf extracts against three mosquito species (diptera: culicidae). | the resistance status of malaria vectors to different classes of insecticides used for public health has raised concern for vector control programmes. alternative compounds to supplement the existing tools are important to be searched to overcome the existing resistance and persistence of pesticides in vectors and the environment respectively. the mosquitocidal effects of glycosmis pentaphylla using different solvents of acetone, methanol, chloroform and ethyl acetate extracts against three medi ... | 2016 | 27391146 |
| biodiversity and activity of the gut microbiota across the life history of the insect herbivore spodoptera littoralis. | microbes that live inside insects play critical roles in host nutrition, physiology, and behavior. although lepidoptera (butterflies and moths) are one of the most diverse insect taxa, their microbial symbionts are little-studied, particularly during metamorphosis. here, using ribosomal tag pyrosequencing of dna and rna, we investigated biodiversity and activity of gut microbiotas across the holometabolous life cycle of spodoptera littoralis, a notorious agricultural pest worldwide. proteobacter ... | 2016 | 27389097 |
| plasmodium adometdc/odc bifunctional enzyme is essential for male sexual stage development and mosquito transmission. | polyamines are positively-charged organic molecules that are important for cellular growth and division. polyamines and their synthesizing enzymes are particularly abundant in rapidly proliferating eukaryotic cells such as parasitic protozoa and cancer cells. polyamine biosynthesis inhibitors, such as elfornithine, are now being considered for cancer prevention and have been used effectively against trypanosoma brucei inhibitors of polyamine biosynthesis have caused growth arrest of plasmodium f ... | 2016 | 27387533 |
| overexpression of plasmodium berghei atg8 by liver forms leads to cumulative defects in organelle dynamics and to generation of noninfectious merozoites. | plasmodium parasites undergo continuous cellular renovation to adapt to various environments in the vertebrate host and insect vector. in hepatocytes, plasmodium berghei discards unneeded organelles for replication, such as micronemes involved in invasion. concomitantly, intrahepatic parasites expand organelles such as the apicoplast that produce essential metabolites. we previously showed that the atg8 conjugation system is upregulated in p. berghei liver forms and that p. berghei atg8 (pbatg8) ... | 2016 | 27353755 |
| evolution of the transmission-blocking vaccine candidates pvs28 and pvs25 in plasmodium vivax: geographic differentiation and evidence of positive selection. | transmission-blocking (tb) vaccines are considered an important tool for malaria control and elimination. among all the antigens characterized as tb vaccines against plasmodium vivax, the ookinete surface proteins pvs28 and pvs25 are leading candidates. these proteins likely originated by a gene duplication event that took place before the radiation of the known plasmodium species to primates. we report an evolutionary genetic analysis of a worldwide sample of pvs28 and pvs25 alleles. our result ... | 2016 | 27347876 |
| sas6-like protein in plasmodium indicates that conoid-associated apical complex proteins persist in invasive stages within the mosquito vector. | the sas6-like (sas6l) protein, a truncated paralogue of the ubiquitous basal body/centriole protein sas6, has been characterised recently as a flagellum protein in trypanosomatids, but associated with the conoid in apicomplexan toxoplasma. the conoid has been suggested to derive from flagella parts, but is thought to have been lost from some apicomplexans including the malaria-causing genus plasmodium. presence of sas6l in plasmodium, therefore, suggested a possible role in flagella assembly in ... | 2016 | 27339728 |
| de novo transcriptome analysis of the common new zealand stick insect clitarchus hookeri (phasmatodea) reveals genes involved in olfaction, digestion and sexual reproduction. | phasmatodea, more commonly known as stick insects, have been poorly studied at the molecular level for several key traits, such as components of the sensory system and regulators of reproduction and development, impeding a deeper understanding of their functional biology. here, we employ de novo transcriptome analysis to identify genes with primary functions related to female odour reception, digestion, and male sexual traits in the new zealand common stick insect clitarchus hookeri (white). the ... | 2016 | 27336743 |
| does fluoride influence oviposition of anopheles stephensi in stored water habitats in an urban setting? | the physico-chemical characteristics of lentic aquatic habitats greatly influence mosquito species in selecting suitable oviposition sites; immature development, pupation and adult emergence, therefore are considerations for their preferred ecological niche. correlating water quality parameters with mosquito breeding, as well as immature vector density, are useful for vector control operations in identifying and targeting potential breeding habitats. | 2016 | 27829419 |
| identification and characterization of micrornas expressed in the african malaria vector anopheles funestus life stages using high throughput sequencing. | over the past several years, thousands of micrornas (mirnas) have been identified in the genomes of various insects through cloning and sequencing or even by computational prediction. however, the number of mirnas identified in anopheline species is low and little is known about their role. the mosquito anopheles funestus is one of the dominant malaria vectors in africa, which infects and kills millions of people every year. therefore, small rna molecules isolated from the four life stages (eggs ... | 2016 | 27825380 |
| a monoclonal antibody-based immunoassay to measure the antibody response against the repeat region of the circumsporozoite protein of plasmodium falciparum. | the malaria vaccine candidate rts,s/as01 (gsk vaccines) induces high igg concentration against the circumsporozoite protein (csp) of plasmodium falciparum. in human vaccine recipients circulating anti-csp antibody concentrations are associated with protection against infection but appear not to be the correlate of protection. however, in a humanized mouse model of malaria infection prophylactic administration of a human monoclonal antibody (mal1c), derived from a rts,s/as01-immunized volunteer, ... | 2016 | 27825382 |
| angiotensin ii type-1 receptor (at1r) regulates expansion, differentiation, and functional capacity of antigen-specific cd8(+) t cells. | angiotensin ii (ang ii) and its receptor at1 (at1r), an important effector axis of renin-angiotensin system (ras), have been demonstrated to regulate t-cell responses. however, these studies characterized ang ii and at1r effects using pharmacological tools, which do not target only ang ii/at1r axis. the specific role of at1r expressed by antigen-specific cd8(+) t cells is unknown. then we immunized transgenic mice expressing a t-cell receptor specific for siinfekl epitope (ot-i mice) with sporoz ... | 2016 | 27782175 |
| safety and immunogenicity of pfs25-epa/alhydrogel®, a transmission blocking vaccine against plasmodium falciparum: an open label study in malaria naïve adults. | transmission-blocking vaccines (tbvs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. pfs25 is a leading tbv candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to epa, a recombinant, detoxified exoprotein a from pseudomonas aeruginosa. in this report, we describe results of an open-label, dose-escalating phase 1 trial to assess the safety and immunogenicit ... | 2016 | 27749907 |
| vorticella sp: prospective mosquito biocontrol agent. | considering the disadvantages of chemical insecticides, we aimed to evaluate vorticella parasites for control of mosquito larvae of anopheles stephensi and aedes aegypti at different larval stages. | 2016 | 28032113 |
| chemical compositions of the peel essential oil of citrus aurantium and its natural larvicidal activity against the malaria vector anopheles stephensi (diptera: culicidae) in comparison with citrus paradisi. | recently, essential oils and extracts derived from plants have received much interest as potential bio-active agents against mosquito vectors. | 2016 | 28032110 |
| laboratory evaluation of temephos against anopheles stephensi and culex pipiens larvae in iran. | malaria is still a health problem in iran. there are several vector control activities, including indoor residual spraying, using insecticide treated nets and larviciding including temephos. in addition nuisance mosquitos are prevalent in the urban areas. so that evaluation of this species to larvicide will provide a clue for management of vector control activities. | 2016 | 28032103 |
| current susceptibility status of anopheles stephensi (diptera: culicidae) to different imagicides in a malarious area, southeastern of iran. | anopheles mosquitoes are an important group of arthropods due to their role in transmission of malaria. the present study was conducted for determination of susceptibility status of anopheles stephensi to different imagicides collected from malarious area in chabahar city, iran. | 2016 | 28032101 |
| characterization of novel antimalarial compound act-451840: preclinical assessment of activity and dose-efficacy modeling. | artemisinin resistance observed in southeast asia threatens the continued use of artemisinin-based combination therapy in endemic countries. additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. herein, the preclinical characterization of one of these com ... | 2016 | 27701420 |
| characterization and expression profiling of atp-binding cassette transporter genes in the diamondback moth, plutella xylostella (l.). | atp-binding cassette (abc) transporters are one of the major transmembrane protein families found in all organisms and play important roles in transporting a variety of compounds across intra and extra cellular membranes. in some species, abc transporters may be involved in the detoxification of substances such as insecticides. the diamondback moth, plutella xylostella (l.), a destructive pest of cruciferous crops worldwide, is an important species to study as it is resistant to many types of in ... | 2016 | 27678067 |
| guy1 confers complete female lethality and is a strong candidate for a male-determining factor in anopheles stephensi. | despite their importance in sexual differentiation and reproduction, y chromosome genes are rarely described because they reside in repeat-rich regions that are difficult to study. here, we show that guy1, a unique y chromosome gene of a major urban malaria mosquito anopheles stephensi, confers 100% female lethality when placed on the autosomes. we show that the small guy1 protein (56 amino acids in length) causes female lethality and that males carrying the transgene are reproductively more com ... | 2016 | 27644420 |
| genetic characterization of plasmodium putative pantothenate kinase genes reveals their essential role in malaria parasite transmission to the mosquito. | the metabolic machinery for the biosynthesis of coenzyme a (coa) from exogenous pantothenic acid (vitamin b5) has long been considered as an excellent target for the development of selective antimicrobials. earlier studies in the human malaria parasite plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. although two eukaryotic-type putative pantothenate kinase genes (pank1 and pank2) have been identifie ... | 2016 | 27644319 |
| cedrol, a malaria mosquito oviposition attractant is produced by fungi isolated from rhizomes of the grass cyperus rotundus. | cedrol, a sesquiterpene alcohol, is the first identified oviposition attractant for african malaria vectors. finding the natural source of this compound might help to elucidate why anopheles gambiae and anopheles arabiensis prefer to lay eggs in habitats containing it. previous studies suggest that cedrol may be a fungal metabolite and the essential oil of grass rhizomes have been described to contain a high amount of different sesquiterpenes. | 2016 | 27639972 |
| an inter-laboratory comparison of standard membrane-feeding assays for evaluation of malaria transmission-blocking vaccines. | an effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological assay is essential for its development. the standard membrane-feeding assay (smfa) for plasmodium falciparum infection of mosquitoes is considered a "gold standard" assay to measure transmission-blocking activity of test antibodies, and has been utilized widely in both non-clinical and clinical studies. while several studies have discussed the inherent variability ... | 2016 | 27612458 |
| recent advances in malaria genomics and epigenomics. | malaria continues to impose a significant disease burden on low- and middle-income countries in the tropics. however, revolutionary progress over the last 3 years in nucleic acid sequencing, reverse genetics, and post-genome analyses has generated step changes in our understanding of malaria parasite (plasmodium spp.) biology and its interactions with its host and vector. driven by the availability of vast amounts of genome sequence data from plasmodium species strains, relevant human population ... | 2016 | 27605022 |
| inhibition of malaria infection in transgenic anopheline mosquitoes lacking salivary gland cells. | malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. the salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. moreover, salivary gland c ... | 2016 | 27598328 |
| plasmodium cynomolgi infections in rhesus macaques display clinical and parasitological features pertinent to modelling vivax malaria pathology and relapse infections. | plasmodium vivax infections in humans or in new world monkeys pose research challenges that necessitate the use of alternative model systems. plasmodium cynomolgi is a closely related species that shares genetic and biological characteristics with p. vivax, including relapses. here, the haematological dynamics and clinical presentation of sporozoite-initiated p. cynomolgi infections in macaca mulatta (rhesus macaques) are evaluated over a 100-day period. | 2016 | 27590312 |
| human cd8+ t cells mediate protective immunity induced by a human malaria vaccine in human immune system mice. | a number of studies have shown that cd8+ t cells mediate protective anti-malaria immunity in a mouse model. however, whether human cd8+ t cells play a role in protection against malaria remains unknown. we recently established human immune system (his) mice harboring functional human cd8+ t cells (his-cd8 mice) by transduction with hla-a∗0201 and certain human cytokines using recombinant adeno-associated virus-based gene transfer technologies. these his-cd8 mice mount a potent, antigen-specific ... | 2016 | 27502569 |
| silencing of anopheles stephensi heme peroxidase hpx15 activates diverse immune pathways to regulate the growth of midgut bacteria. | anopheles mosquito midgut harbors a diverse group of endogenous bacteria that grow extensively after the blood feeding and help in food digestion and nutrition in many ways. although, the growth of endogenous bacteria is regulated by various factors, however, the robust antibacterial immune reactions are generally suppressed in this body compartment by a heme peroxidase hpx15 crosslinked mucins barrier. this barrier is formed on the luminal side of the midgut and blocks the direct interactions a ... | 2016 | 27630620 |
| effects of environment, dietary regime and ageing on the dengue vector microbiota: evidence of a core microbiota throughout aedes aegypti lifespan. | mosquito midgut microbiota is a key component of vector competence, as gut bacteria can disturb pathogen development. in this study, we addressed the microbiota composition of aedes aegypti during its lifespan, under field conditions. we also investigated the possible effects of environment, dietary regime and ageing on the gut community composition. we employed culture independent and dependent approaches to characterise vector microbiota. there was evidence of a lifelong stable core microbiota ... | 2016 | 27580348 |
| seminal fluid protein genes of the brown planthopper, nilaparvata lugens. | seminal fluid proteins (sfps) are produced mainly in the accessory gland of male insects and transferred to females during mating, in which they induce numerous physiological and post-mating behavioral changes. the brown plant hopper (bph), nilaparvata lugens, is an economically important hemipterous pest of rice. the behavior and physiology of the female of this species is significantly altered by mating. sfps in hemipteran species are still unclear. | 2016 | 27538518 |
| transcriptomic evidence for modulation of host inflammatory responses during febrile plasmodium falciparum malaria. | identifying molecular predictors and mechanisms of malaria disease is important for understanding how plasmodium falciparum malaria is controlled. transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. in this prospective, proof-of-principle study, we compared whole-blood rna-seq profiles at pre-and post-infection time points from malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during their first seasonal pc ... | 2016 | 27506615 |
| effects of transmission-blocking vaccines simultaneously targeting pre- and post-fertilization antigens in the rodent malaria parasite plasmodium yoelii. | transmission-blocking vaccine (tbv) is a promising strategy for interrupting the malaria transmission cycle. current tbv candidates include both pre- and post-fertilization antigens expressed during sexual development of the malaria parasites. | 2016 | 27502144 |
| diagnosis and treatment based on quantitative pcr after controlled human malaria infection. | controlled human malaria infection (chmi) has become well-established in the evaluation of drugs and vaccines. anti-malarial treatment is usually initiated when thick blood smears are positive by microscopy. this study explores the effects of using the more sensitive qpcr as the primary diagnostic test. | 2016 | 27495296 |
| characterization of the plasmodium falciparum and p. berghei glycerol 3-phosphate acyltransferase involved in fasii fatty acid utilization in the malaria parasite apicoplast. | malaria parasites can synthesize fatty acids via a type ii fatty acid synthesis (fasii) pathway located in their apicoplast. the fasii pathway has been pursued as an anti-malarial drug target, but surprisingly little is known about its role in lipid metabolism. here we characterize the apicoplast glycerol 3-phosphate acyltransferase that acts immediately downstream of fasii in human (plasmodium falciparum) and rodent (plasmodium berghei) malaria parasites and investigate how this enzyme contribu ... | 2016 | 27324409 |
| discovery of point mutations in the voltage-gated sodium channel from african aedes aegypti populations: potential phylogenetic reasons for gene introgression. | yellow fever is endemic in some countries in africa, and aedes aegpyti is one of the most important vectors implicated in the outbreak. the mapping of the nation-wide distribution and the detection of insecticide resistance of vector mosquitoes will provide the beneficial information for forecasting of dengue and yellow fever outbreaks and effective control measures. | 2016 | 27304430 |
| neem oil and crop protection: from now to the future. | a major challenge of agriculture is to increase food production to meet the needs of the growing world population, without damaging the environment. in current agricultural practices, the control of pests is often accomplished by means of the excessive use of agrochemicals, which can result in environmental pollution and the development of resistant pests. in this context, biopesticides can offer a better alternative to synthetic pesticides, enabling safer control of pest populations. however, l ... | 2016 | 27790224 |
| organization of olfactory centres in the malaria mosquito anopheles gambiae. | mosquitoes are vectors for multiple infectious human diseases and use a variety of sensory cues (olfactory, temperature, humidity and visual) to locate a human host. a comprehensive understanding of the circuitry underlying sensory signalling in the mosquito brain is lacking. here we used the q-system of binary gene expression to develop transgenic lines of anopheles gambiae in which olfactory receptor neurons expressing the odorant receptor co-receptor (orco) gene are labelled with gfp. these n ... | 2016 | 27694947 |
| tyrosine hydroxylase is crucial for maintaining pupal tanning and immunity in anopheles sinensis. | tyrosine hydroxylase (th), the initial enzyme in the melanin pathway, catalyzes tyrosine conversion into dopa. although expression and regulation of th have been shown to affect cuticle pigmentation in insects, no direct functional studies to date have focused on the specific physiological processes involving the enzyme during mosquito development. in the current study, silencing of asth during the time period of continuous high expression in anopheles sinensis pupae led to significant impairmen ... | 2016 | 27416870 |
| neemazal ® as a possible alternative control tool for malaria and african trypanosomiasis? | research efforts to identify possible alternative control tools for malaria and african trypanosomiasis are needed. one promising approach relies on the use of traditional plant remedies with insecticidal activities. | 2016 | 27146309 |
| differential effects of azithromycin, doxycycline, and cotrimoxazole in ingested blood on the vectorial capacity of malaria mosquitoes. | background. the gut microbiota of malaria vector mosquitoes grows after a blood meal and limits plasmodium infection. we previously showed that penicillin and streptomycin in the ingested blood affect bacterial growth and positively impact mosquito survival and permissiveness to plasmodium. in this study, we examine the effects of doxycycline, azithromycin, and co-trimoxazole. all 3 antibiotics are used in mass drug administration programs and have antimicrobial activities against bacteria and ... | 2016 | 27419152 |
| radical remodeling of the y chromosome in a recent radiation of malaria mosquitoes. | y chromosomes control essential male functions in many species, including sex determination and fertility. however, because of obstacles posed by repeat-rich heterochromatin, knowledge of y chromosome sequences is limited to a handful of model organisms, constraining our understanding of y biology across the tree of life. here, we leverage long single-molecule sequencing to determine the content and structure of the nonrecombining y chromosome of the primary african malaria mosquito, anopheles g ... | 2016 | 27035980 |
| comparison of irradiation and wolbachia based approaches for sterile-male strategies targeting aedes albopictus. | the global expansion of aedes albopictus together with the absence of vaccines for most of the arboviruses transmitted by this mosquito has stimulated the development of sterile-male strategies aiming at controlling disease transmission through the suppression of natural vector populations. in this context, two environmentally friendly control strategies, namely the sterile insect technique (sit) and the wolbachia-based incompatible insect technique (iit) are currently being developed in several ... | 2016 | 26765951 |
| epidemiology and control of plasmodium vivax in afghanistan. | around half of the population of afghanistan resides in areas at risk of malaria transmission. two species of malaria (plasmodium vivax and plasmodium falciparum) account for a high burden of disease-in 2011, there were more than 300,000 confirmed cases. around 80-95% of malaria is p. vivax transmission is seasonal and focal, below 2,000 m in altitude, and in irrigated areas which allow breeding of anopheline mosquito vectors. malaria risk is stratified to improve targeting of interventions. six ... | 2016 | 27708189 |
| insecticide susceptibility of anopheles stephensi to ddt and current insecticides in an elimination area in iran. | iran has recently initiated a malaria elimination program with emphasis on vector control strategies which are heavily reliant on indoor residual spraying and long-lasting insecticidal nets. insecticide resistance seriously threatens the efficacy of vector control strategies. this study was conducted to determine the insecticide susceptibility of anopheles stephensi to ddt and current insecticides in jask county as an active malaria focus in southeastern iran. | 2016 | 27809871 |
| heterogeneous malaria transmission in long-term afghan refugee populations: a cross-sectional study in five refugee camps in northern pakistan. | afghan refugees in northern pakistan have been resident for over 30 years and current information on malaria in this population is sparse. understanding malaria risk and distribution in refugee camps is important for effective management both in camps and on return to afghanistan. | 2016 | 27121196 |
| mind the gap: residual malaria transmission, veterinary endectocides and livestock as targets for malaria vector control. | 2016 | 26755345 | |
| status of insecticide resistance in high-risk malaria provinces in afghanistan. | insecticide resistance seriously threatens the efficacy of vector control interventions in malaria endemic countries. in afghanistan, the status of insecticide resistance is largely unknown while distribution of long-lasting insecticidal nets has intensified in recent years. the main objective of this study was thus to measure the level of resistance to four classes of insecticides in provinces with medium to high risk of malaria transmission. | 2016 | 26888409 |
| a review of bioinsecticidal activity of solanaceae alkaloids. | only a small percentage of insect species are pests. however, pest species cause significant losses in agricultural and forest crops, and many are vectors of diseases. currently, many scientists are focused on developing new tools to control insect populations, including secondary plant metabolites, e.g., alkaloids, glycoalkaloids, terpenoids, organic acids and alcohols, which show promise for use in plant protection. these compounds can affect insects at all levels of biological organization, b ... | 2016 | 26938561 |
| intra-instar larval cannibalism in anopheles gambiae (s.s.) and anopheles stephensi (diptera: culicidae). | cannibalism has been observed in a wide range of animal taxa and its importance in persistence and stability of populations has been documented. in anopheline malaria vectors the inter-instar cannibalism between fourth- and first-instar larvae (l4-l1) has been shown in several species, while intra-instar cannibalism remains poorly investigated. in this study we tested the occurrence of intra-instar cannibalism within larvae of second-, third- and fourth-instar (l2, l3 and l4) of anopheles gambia ... | 2016 | 27806728 |
| identification of immunity-related genes in dialeurodes citri against entomopathogenic fungus lecanicillium attenuatum by rna-seq analysis. | dialeurodes citri is a major pest in citrus producing areas, and large-scale outbreaks have occurred increasingly often in recent years. lecanicillium attenuatum is an important entomopathogenic fungus that can parasitize and kill d. citri. we separated the fungus from corpses of d. citri larvae. however, the sound immune defense system of pests makes infection by an entomopathogenic fungus difficult. here we used rna sequencing technology (rna-seq) to build a transcriptome database for d. citri ... | 2016 | 27644092 |
| molecular diversity between salivary proteins from new world and old world sand flies with emphasis on bichromomyia olmeca, the sand fly vector of leishmania mexicana in mesoamerica. | sand fly saliva has been shown to have proteins with potent biological activities, salivary proteins that can be used as biomarkers of vector exposure, and salivary proteins that are candidate vaccines against different forms of leishmaniasis. sand fly salivary gland transcriptomic approach has contributed significantly to the identification and characterization of many of these salivary proteins from important leishmania vectors; however, sand fly vectors in some regions of the world are still ... | 2016 | 27409591 |
| a crispr-cas9 sex-ratio distortion system for genetic control. | genetic control aims to reduce the ability of insect pest populations to cause harm via the release of modified insects. one strategy is to bias the reproductive sex ratio towards males so that a population decreases in size or is eliminated altogether due to a lack of females. we have shown previously that sex ratio distortion can be generated synthetically in the main human malaria vector anopheles gambiae, by selectively destroying the x-chromosome during spermatogenesis, through the activity ... | 2016 | 27484623 |
| mating-induced transcriptome changes in the reproductive tract of female aedes aegypti. | the aedes aegypti mosquito is a significant public health threat, as it is the main vector of dengue and chikungunya viruses. disease control efforts could be enhanced through reproductive manipulation of these vectors. previous work has revealed a relationship between male seminal fluid proteins transferred to females during mating and female post-mating physiology and behavior. to better understand this interplay, we used short-read rna sequencing to identify gene expression changes in the low ... | 2016 | 26901677 |
| the use of mosquito repellents at three sites in india with declining malaria transmission: surveys in the community and clinic. | repellents such as coils, vaporizers, mats and creams can be used to reduce the risk of malaria and other infectious diseases. although evidence for their effectiveness is limited, they are advertised as providing an additional approach to mosquito control in combination with other strategies, e.g. insecticide-treated nets. we examined the use of repellents in india in an urban setting in chennai (mainly plasmodium vivax malaria), a peri-urban setting in nadiad (both p. vivax and p. falciparum m ... | 2016 | 27465199 |
| assessment of angelica sinensis (oliv.) diels as a repellent for personal protection against mosquitoes under laboratory and field conditions in northern thailand. | angelica sinensis (oliv.) hexane extract (ahe) has been reported as a proven and impressive repellent against laboratory-reared female aedes aegypti mosquitoes. with the aim of promoting products of plant origin as a viable alternative to conventional synthetic substances, this study was designed to transform ahe-based repellents for exploitable commercial production by enhancing their efficacy and assessing their physical and biological stability as well as repellency against mosquitoes under l ... | 2016 | 27357395 |
| do mosquitoes transmit the avian malaria-like parasite haemoproteus? an experimental test of vector competence using mosquito saliva. | the life-cycle of many vector-borne pathogens includes an asexual replication phase in the vertebrate host and sexual reproduction in the insect vector. however, as only a small array of parasites can successfully develop infective phases inside an insect, few insect species are competent vectors for these pathogens. molecular approaches have identified the potential insect vectors of blood parasites under natural conditions. however, the effectiveness of this methodology for verifying mosquito ... | 2016 | 27894354 |
| plant virus-insect vector interactions: current and potential future research directions. | acquisition and transmission by an insect vector is central to the infection cycle of the majority of plant pathogenic viruses. plant viruses can interact with their insect host in a variety of ways including both non-persistent and circulative transmission; in some cases, the latter involves virus replication in cells of the insect host. replicating viruses can also elicit both innate and specific defense responses in the insect host. a consistent feature is that the interaction of the virus wi ... | 2016 | 27834855 |
| an increase of larval rearing temperature does not affect the susceptibility of phlebotomus sergenti to leishmania tropica but effectively eliminates the gregarine psychodiella sergenti. | in mosquitoes, it has previously been shown that rearing conditions of immature stages have an effect on the vector competence of adults. here, we studied the impact of different larval rearing temperatures (27 °c versus 32 °c) on the sand fly phlebotomus sergenti parrot, 1917 and its susceptibility to two parasites: leishmania tropica wright, 1903, a dixenous trypanosomatid transmissible from sand flies to humans, and psychodiella sergenti lantova, volf & votypka, 2010, a monoxenous sand fly gr ... | 2016 | 27756429 |
| screening of methanolic plant extracts against larvae of aedes aegypti and anopheles stephensi in mysore. | mosquitoes transmit serious human diseases, causing millions of death every year. vector control is facing a threat due to the emergence of resistance to synthetic insecticides. insecticides of botanical origin may serve as suitable alternative biocontrol techniques in the future. nine different locally available medicinally important plants suspected to posse larvicidal property were screened against fourth instar larvae of aedes aegypti and anopheles stephensi to a series of concentrations of ... | 2016 | 27308289 |
| isolation and characterization of native bacillus thuringiensis strains from saudi arabia with enhanced larvicidal toxicity against the mosquito vector anopheles gambiae (s.l.). | worldwide, mosquito vectors are transmitting several etiological agents of important human diseases, including malaria, causing millions of deaths every year. in saudi arabia, as elsewhere, vector-control is based mostly on chemical insecticides which may be toxic and cause environmental deprivation. here, to support the development of bio-pesticide alternatives, a study was conducted to identify native bacillus thuringiensis (bt) isolates with improved toxicity against the malaria vector, anoph ... | 2016 | 27993165 |
| comparative studies on the stenogamous and eurygamous behavior of eight anopheles species of the hyrcanus group (diptera: culicidae) in thailand. | establishment of laboratory colony is essential for mosquito-borne-disease research. mating behavior of stenogamous anopheles peditaeniatus and seven eurygamous species (anopheles argyropus, anopheles crawfordi, anopheles nigerrimus, anopheles nitidus, anopheles paraliae (=an. lesteri), anopheles pursati and anopheles sinensis), were investigated and compared in this study. the self-mating success of adult mosquitoes in different size cages at two density resting surface (drs) values, 3.6 and 7. ... | 2016 | 27023618 |
| endogenously-expressed nh2-terminus of circumsporozoite protein interferes with sporozoite invasion of mosquito salivary glands. | the circumsporozoite protein is the most abundant polypeptide expressed by sporozoites, the malaria parasite stage capable of infecting humans. sporozoite invasion of mosquito salivary glands prior to transmission is likely mediated by a receptor/ligand-like interaction of the parasites with the target tissues, and the amino (nh2)-terminal portion of csp is involved in this interaction but not the tsr region on the carboxyl (c)-terminus. peptides based on the nh2-terminal domain could compete wi ... | 2016 | 26964736 |
| assessment of pfs25 expressed from multiple soluble expression platforms for use as transmission-blocking vaccine candidates. | transmission-blocking vaccines (tbvs) have become a focus of strategies to control and eventually eliminate malaria as they target the entry of sexual stage into the anopheles stephensi mosquito thereby preventing transmission, an essential component of the parasite life cycle. such vaccines are envisioned as complements to vaccines that target human infection, such as rts,s as well as drug treatment, and vector control strategies. a number of conserved proteins, including pfs25, have been ident ... | 2016 | 27515826 |
| viral metagenomics on blood-feeding arthropods as a tool for human disease surveillance. | surveillance and monitoring of viral pathogens circulating in humans and wildlife, together with the identification of emerging infectious diseases (eids), are critical for the prediction of future disease outbreaks and epidemics at an early stage. it is advisable to sample a broad range of vertebrates and invertebrates at different temporospatial levels on a regular basis to detect possible candidate viruses at their natural source. however, virus surveillance systems can be expensive, costly i ... | 2016 | 27775568 |
| the sandfly lutzomyia longipalpis ll5 embryonic cell line has active toll and imd pathways and shows immune responses to bacteria, yeast and leishmania. | lutzomyia longipalpis is the main vector of visceral leishmaniasis in latin america. sandfly immune responses are poorly understood. in previous work we showed that these vector insects respond to bacterial infections by modulating a defensin gene expression and activate the imd pathway in response to leishmania infection. aspects of innate immune pathways in insects (including mosquito vectors of human diseases) have been revealed by studying insect cell lines, and we have previously demonstrat ... | 2016 | 27098567 |
| diet-induced nutritional stress and pathogen interference in wolbachia-infected aedes aegypti. | the pathogen interference phenotype greatly restricts infection with dengue virus (denv) and other pathogens in wolbachia-infected aedes aegypti, and is a vital component of wolbachia-based mosquito control. critically, the phenotype's causal mechanism is complex and poorly understood, with recent evidence suggesting that the cause may be species specific. to better understand this important phenotype, we investigated the role of diet-induced nutritional stress on interference against denv and t ... | 2016 | 27893736 |
| in silico study on anti-chikungunya virus activity of hesperetin. | the re-emerging, aedes spp. transmitted chikungunya virus (chikv) has recently caused large outbreaks in a wide geographical distribution of the world including countries in europe and america. though fatalities associated with this self-remitting disease were rarely reported, quality of patients' lives have been severely diminished by polyarthralgia recurrence. neither effective antiviral treatment nor vaccines are available for chikv. our previous in vitro screening showed that hesperetin, a b ... | 2016 | 27812412 |
| larvicidal potential of the halogenated sesquiterpene (+)-obtusol, isolated from the alga laurencia dendroidea j. agardh (ceramiales: rhodomelaceae), against the dengue vector mosquito aedes aegypti (linnaeus) (diptera: culicidae). | dengue is considered a serious public health problem in many tropical regions of the world including brazil. at the moment, there is no viable alternative to reduce dengue infections other than controlling the insect vector, aedes aegypti linnaeus. in the continuing search for new sources of chemicals targeted at vector control, natural products are a promising alternative to synthetic pesticides. in our work, we investigated the toxicity of a bioactive compound extracted from the red alga laure ... | 2016 | 26821032 |
| prospects and challenges of crispr/cas genome editing for the study and control of neglected vector-borne nematode diseases. | neglected tropical diseases caused by parasitic nematodes inflict an immense health and socioeconomic burden throughout much of the developing world. current estimates indicate that more than two billion people are infected with nematodes, resulting in the loss of 14 million disability-adjusted life years per annum. although these parasites cause significant mortality, they primarily cause chronic morbidity through a wide range of severe clinical ailments. treatment options for nematode infectio ... | 2016 | 27300487 |
| epidemiology of plasmodium vivax malaria in india. | historically, malaria in india was predominantly caused by plasmodium vivax, accounting for 53% of the estimated cases. after the spread of drug-resistant plasmodium falciparum in the 1990s, the prevalence of the two species remained equivalent at the national level for a decade. by 2014, the proportion of p. vivax has decreased to 34% nationally, but with high regional variation. in 2014, p. vivax accounted for around 380,000 malaria cases in india; almost a sixth of all p. vivax cases reported ... | 2016 | 27708188 |
| time series analysis of malaria in afghanistan: using arima models to predict future trends in incidence. | malaria remains endemic in afghanistan. national control and prevention strategies would be greatly enhanced through a better ability to forecast future trends in disease incidence. it is, therefore, of interest to develop a predictive tool for malaria patterns based on the current passive and affordable surveillance system in this resource-limited region. | 2016 | 27876041 |
| plasmodium vivax msp-3α polymorphisms: analysis in the indian subcontinent. | plasmodium vivax is the most widely distributed human malaria parasite and accounts for approximately the same number of malaria cases as plasmodium falciparum in india. compared with p. falciparum, p. vivax is difficult to eradicate because of its tendency to cause relapses, which impacts treatment and control strategies. the genetic diversity of these parasites, particularly of the merozoite surface protein-3 alpha (msp-3α) gene, can be used to help develop a potential vaccine. the present stu ... | 2016 | 27663527 |
| an experimental hut evaluation of olyset plus, a long-lasting insecticidal net treated with a mixture of permethrin and piperonyl butoxide, against anopheles fluviatilis in odisha state, india. | fast development of pyrethroid resistance in malaria vectors prompted the development of new vector control tools including combination of insecticides with different modes of action as part of resistance management strategies. olyset plus® is a new long-lasting insecticidal net, in which, permethrin and a synergist, piperonyl butoxide (pbo), are incorporated into filaments. mixture nets such as this may have application against resistant mosquitoes, particularly those whose resistance is based ... | 2016 | 27439398 |
| distribution of malaria vectors and incidence of vivax malaria at korean army installations near the demilitarized zone, republic of korea. | as a result of the reintroduction of malaria in the republic of korea (rok) in 1993 and the threat to military and civilian populations, the korea military national defense (mnd) increased emphasis on vector control in 2012 at rok army (roka) installations located near the dmz, while decreasing chemoprophylaxis, fearing potential drug resistance. mosquito surveillance demonstrated a need for continuous monitoring of disease patterns among roka soldiers and vector malaria infection rates to ensur ... | 2016 | 27150110 |
| anopheles subpictus carry human malaria parasites in an urban area of western india and may facilitate perennial malaria transmission. | india contributes 1.5-2 million annual confirmed cases of malaria. since both parasites and vectors are evolving rapidly, updated information on parasite prevalence in mosquitoes is important for vector management and disease control. possible new vector-parasite interactions in goa, india were tested. | 2016 | 26919828 |
| susceptibility status of anopheles arabiensis (diptera: culicidae) commonly used as biological materials for evaluations of malaria vector control tools in madagascar. | madagascar is a malaria-endemic country with an increase in cases in recent years. in vector control using insecticide, a susceptible strain is necessary to evaluate insecticide efficacy, either for spraying or on nets. the susceptibility of anopheles arabiensis from antananarivo, madagascar to two organophosphate, three pyrethroid, two carbamate, and one organochlorine insecticides was investigated. since 2010, an. arabiensis strain has been maintained away from insecticide source during 110 ge ... | 2016 | 27364163 |
| salivary gland proteome during adult development and after blood feeding of female anopheles dissidens mosquitoes (diptera: culicidae). | understanding changes in mosquito salivary proteins during the time that sporozoite maturation occurs and after blood feeding may give information regarding the roles of salivary proteins during the malarial transmission. anopheles dissidens (formerly anopheles barbirostris species a1) is a potential vector of plasmodium vivax in thailand. in this study, analyses of the proteomic profiles of female an. dissidens salivary glands during adult development and after blood feeding were carried out us ... | 2016 | 27669021 |