Competency of Anopheles stephensi mysorensis strain for Plasmodium vivax and the role of inhibitory carbohydrates to block its sporogonic cycle

<p>Abstract</p> <p>Background</p> <p>Despite the abundance of studies conducted on the role of mosquitoes in malaria transmission, the biology and interaction of <it>Plasmodium </it>with its insect host still holds many mysteries. This paper provides the first study to follow the sporogonic cycle of <it>Plasmodium vivax </it>in a wild insecticide-resistant mysorensis strain of <it>Anopheles stephensi</it>, a major vector of vivax malaria in south-eastern Iran. The study subsequently demonstrates that host-parasite sugar binding interactions are critical to the development of this parasite in the salivary glands of its mosquito host. The identity of the receptors or sugars involved was revealed by a receptor "pre-saturation" strategy in which sugars fed to the mosquitoes inhibited normal host-parasite interactions.</p> <p>Methods</p> <p><it>Anopheles stephensi </it>mysorensis mosquitoes were artificially infected with <it>P. vivax </it>by feeding on the blood of gametocytaemic volunteers reporting to local malaria clinics in the Sistan-Baluchistan province of south-eastern Iran. In order to determine the inhibitory effect of carbohydrates on sporogonic development, vector mosquitoes were allowed to ingest blood meals containing both gametocytes and added carbohydrates. The carbohydrates tested were GlcNAc, GalNAc, arabinose, fucose, mannose, lactose, glucose and galactose. Sporogonic development was assessed by survival of the parasite at both the oocyst and sporozoite stages.</p> <p>Results</p> <p>Oocyst development was observed among nearly 6% of the fed control mosquitoes but the overall number of mosquitoes exhibiting sporozoite invasion of the salivary glands was 47.5% lower than the number supporting oocysts in their midgut. Of the tested carbohydrates, only arabinose and fucose slightly perturbed the development of <it>P. vivax </it>oocysts at the basal side of the mosquito midgut, and the remaining sugars caused no reductions in oocyst development. Strikingly however, sporozoites were completely absent from the salivary glands of mosquitoes treated with mannose, GalNAc, and lactose.</p> <p>Conclusion</p> <p>The study indicates that <it>An. stephensi </it>in southern Iran has the potential to survive long enough to be re-infected and transmit vivax malaria several times, based on the average adult female longevity (about 30 days) and its gonotrophic cycle (2–3 days) during the malaria transmission season. Certain sugar binding interactions are important for the development of <it>P. vivax </it>sporozoites, and this information may be instrumental for the development of transmission blocking strategies.</p

Information-theoretic principle entails orthomodularity of a lattice

Quantum logical axiomatic systems for quantum theory usually include a postulate that a lattice under consideration is orthomodular. We propose a derivation of orthomodularity from an information-theoretic axiom. This provides conceptual clarity and removes a long-standing puzzle about the meaning of orthomodularity.Comment: Version prior to published, with slight modification

Anopheles Gambiae PRS1 Modulates Plasmodium Development at Both Midgut and Salivary Gland Steps

Background: Invasion of the mosquito salivary glands by Plasmodium is a critical step for malaria transmission. From a SAGE analysis, we previously identified several genes whose expression in salivary glands was regulated coincident with sporozoite invasion of salivary glands. To get insights into the consequences of these salivary gland responses, here we have studied one of the genes, PRS1 (Plasmodium responsive salivary 1), whose expression was upregulated in infected glands, using immunolocalization and functional inactivation approaches. Methodology/Principal Findings: PRS1 belongs to a novel insect superfamily of genes encoding proteins with DM9 repeat motifs of uncharacterized function. We show that PRS1 is induced in response to Plasmodium, not only in the salivary glands but also in the midgut, the other epithelial barrier that Plasmodium has to cross to develop in the mosquito. Furthermore, this induction is observed using either the rodent parasite Plasmodium berghei or the human pathogen Plasmodium falciparum. In the midgut, PRS1 overexpression is associated with a relocalization of the protein at the periphery of invaded cells. We also find that sporozoite invasion of salivary gland cells occurs sequentially and induces intra-cellular modifications that include an increase in PRS1 expression and a relocalization of the corresponding protein into vesicle-like structures. Importantly, PRS1 knockdown during the onset of midgut and salivary gland invasion demonstrates that PRS1 acts as an agonist for the development of both parasite species in the two epithelia, highlighting shared vector/parasite interactions in both tissues. Conclusions/Significance: While providing insights into potential functions of DM9 proteins, our results reveal that PRS1 likely contributes to fundamental interactions between Plasmodium and mosquito epithelia, which do not depend on the specific Anopheles/P. falciparum coevolutionary history

Malaria Parasite Invasion of the Mosquito Salivary Gland Requires Interaction between the Plasmodium TRAP and the Anopheles Saglin Proteins

SM1 is a twelve-amino-acid peptide that binds tightly to the Anopheles salivary gland and inhibits its invasion by Plasmodium sporozoites. By use of UV-crosslinking experiments between the peptide and its salivary gland target protein, we have identified the Anopheles salivary protein, saglin, as the receptor for SM1. Furthermore, by use of an anti-SM1 antibody, we have determined that the peptide is a mimotope of the Plasmodium sporozoite Thrombospondin Related Anonymous Protein (TRAP). TRAP binds to saglin with high specificity. Point mutations in TRAP's binding domain A abrogate binding, and binding is competed for by the SM1 peptide. Importantly, in vivo down-regulation of saglin expression results in strong inhibition of salivary gland invasion. Together, the results suggest that saglin/TRAP interaction is crucial for salivary gland invasion by Plasmodium sporozoites

Naturally Occurring Triggers that Induce Apoptosis-Like Programmed Cell Death in Plasmodium berghei Ookinetes

Several protozoan parasites have been shown to undergo a form of programmed cell death that exhibits morphological features associated with metazoan apoptosis. These include the rodent malaria parasite, Plasmodium berghei. Malaria zygotes develop in the mosquito midgut lumen, forming motile ookinetes. Up to 50% of these exhibit phenotypic markers of apoptosis; as do those grown in culture. We hypothesised that naturally occurring signals induce many ookinetes to undergo apoptosis before midgut traversal. To determine whether nitric oxide and reactive oxygen species act as such triggers, ookinetes were cultured with donors of these molecules. Exposure to the nitric oxide donor SNP induced a significant increase in ookinetes with condensed nuclear chromatin, activated caspase-like molecules and translocation of phosphatidylserine that was dose and time related. Results from an assay that detects the potential-dependent accumulation of aggregates of JC-1 in mitochondria suggested that nitric oxide does not operate via loss of mitochondrial membrane potential. L-DOPA (reactive oxygen species donor) also caused apoptosis in a dose and time dependent manner. Removal of white blood cells significantly decreased ookinetes exhibiting a marker of apoptosis in vitro. Inhibition of the activity of nitric oxide synthase in the mosquito midgut epithelium using L-NAME significantly decreased the proportion of apoptotic ookinetes and increased the number of oocysts that developed. Introduction of a nitric oxide donor into the blood meal had no effect on mosquito longevity but did reduce prevalence and intensity of infection. Thus, nitric oxide and reactive oxygen species are triggers of apoptosis in Plasmodium ookinetes. They occur naturally in the mosquito midgut lumen, sourced from infected blood and mosquito tissue. Up regulation of mosquito nitric oxide synthase activity has potential as a transmission blocking strategy

To Cope with the Uncertainity in Smart Energy Systems: Office Buildings as a Source for Energy Flexibility

Electricity energy generation and its supply through electricity networks is mainly organized in a top-down, centralized manner. Energy consumption can be predicted quite accurately at a high level, and this forms the basis for pre-scheduling the production by large power plants. Only few actors are involved in the generation, trade, and transportation of electricity, but this is changing rapidly. Renewable energy conversion (such as wind and solar energy, geothermal energy or as supplied by biomass systems at farms) will lead to a large amount of distributed and fluctuating (small) renewable energy sources throughout the grid, at homes, farms, and companies. The need of centralized electricity generation thus becomes more difficult to plan. This can lead to large problems and unstable electricity grids and therefore we have to develop approaches to deal with this increasing uncertainty. The use of Information and Communication Technology (ICT) and Control Technology (CT) will provide us many options for stabilizing electricity networks. Besides this also on the demand side new consumers such as electric vehicles and heat pumps (with large demand but also high flexibility or storage capacity) appear. The increasing share of decentralized renewable energy conservation in combination with the new types of consumers will drastically alter the operation of electricity systems. Smart Grids are developed by all major electricity distribution companies together with industry to cope with the dispersed electricity production by matching of supply and demand by smart ICT and CT. The future stricter sustainability demands will lead to offices with their own renewable energy sources and energy storage capacity. Office buildings will become a potential source of energy flexibility which can be offered to the grid as a Virtual Power Plant (VPP). In order to minimize uncertainty in the balance between energy supply and demand it is necessary to develop realistic user behavior, installations behavior and Smart Grid interaction. Monitoring the needs and preferences of users is necessary to predict future states of the demand for the SES (e.g. based on weather forecasts and user behavior). Automated prosumer support is needed to optimize interaction between offices and Smart grid