Differential effects of azithromycin, doxycycline and co-trimoxazole 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 various stages of malaria parasites. Methods.  The effects of blood meal supplementation with antibiotics on the mosquito microbiota, lifespan, and permissiveness to Plasmodium falciparum were assessed. Results.  Ingestion of any of the 3 antibiotics significantly affected the mosquito microbiota. Azithromycin decreased P falciparum infection load and mosquito lifespan, whereas at high concentrations, doxycycline increased P falciparum infection load. Co-trimoxazole negatively impacted infection intensity but had no reproducible effect on mosquito lifespan. Conclusions.  Our data suggest that the overall effect of antibiotic treatment on parameters critical for mosquito vectorial capacity is drug specific. The negative effect of azithromycin on malaria transmission is consistent with current efforts for disease elimination, whereas additional, larger scale investigations are required before conclusions can be drawn about doxycycline

The peptidoglycan recognition proteins PGRPLA and PGRPLB regulate Anopheles immunity to bacteria and affect infection by Plasmodium

Peptidoglycan recognition proteins (PGRPs) form a family of immune regulators that is conserved from insects to mammals. In the malaria vector mosquito Anopheles coluzzii , the peptidoglycan receptor PGRPLC activates the Imd pathway limiting both t he microbiota load and Plasmodium infection. Here, we carried out an RNAi screen to examine the rol e of all seven Anopheles PGRPs in infections with Plasmodium berghei and Plasmodium falciparum . We show that, in addition to PGRPLC, PGRPLA and PGRPS2/S3 also participate in antiparas itic defenses, and that PGRPLB promotes mosquito permissiveness to P. falciparum . We also demonstrate that following a mosquito blood feeding, which promotes growth of the gut microbiota, PGRPLA and PGRPLB positively and negatively regulate the activation of the Imd pathway, respective ly. Our data demonstrate that PGRPs are important regulators of the mosquito epithelial immunity and vector comp etence

Seismic monitoring and verification for the Co2CRC Ottway Basin project

The Otway Project conducted under the Australian Cooperative Research Centre for Greenhouse Gas Technologies (CO2CRC) is the first of its kind, where CO2 is injected into a depleted gas reservoir. The use of depleted fields for CO2 storage is likely to become widely adopted globally and, therefore, the project will provide important experience for monitoring under these conditions. However, such scenario is not favorable for the application of geophysical techniques for the purpose of CO2 monitoring and verification (M&V) because the injection of CO2 into a CH4 depleted reservoir is modeled to produce very subtle changes in elastic properties of the reservoir rock which may be very difficult to measure. Consequently geophysical program for the Otway site was design according to the expected time-lapse effects. It combines both surface and borehole seismic methods. Surface seismic should provide a global vision of the underground and an indirect confirmation of the CO2 containment by recording no differences between the successive time-lapse experiments. Vertical Seismic Profile (VSP) surveys are expected to provide an improved characterization of the reservoir and hopefully a direct indication of the fluid distribution and/or its potential upward migration along the reservoir bounding fault pattern. Indeed the results of the current analysis of both pre-base line (test) and base-line 2D and 3D VSP data are encouraging. The availability of vector wave field (three-component) data recorded in VSP surveys should significantly improve the outcomes of M&V program at Naylor site

International equatorial electrojet year : the African sector

International audienceThis paper presents the IEEY project in the African sector. The amount of our interpreted data is presently too short to allow proper scientific conclusions. Nevertheless, fist typical results illustrate our network possibilities. Some preliminary observations are briefly pre- , sented for their interest towards immediate research goals

A streptococcal lipid toxin induces membrane permeabilization and pyroptosis leading to fetal injury

Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newborns. We recently showed that the GBS pigment is hemolytic and increased pigment production promotes bacterial penetration of human placenta. However, mechanisms utilized by the hemolytic pigment to induce host cell lysis and the consequence on fetal injury are not known. Here, we show that the GBS pigment induces membrane permeability in artificial lipid bilayers and host cells. Membrane defects induced by the GBS pigment trigger K+ efflux leading to osmotic lysis of red blood cells or pyroptosis in human macrophages. Macrophages lacking the NLRP3 inflammasome recovered from pigment-induced cell damage. In a murine model of in utero infection, hyperpigmented GBS strains induced fetal injury in both an NLRP3 inflammasome-dependent and NLRP3 inflammasome-independent manner. These results demonstrate that the dual mechanism of action of the bacterial pigment/lipid toxin leading to hemolysis or pyroptosis exacerbates fetal injury and suggest that preventing both activities of the hemolytic lipid is likely critical to reduce GBS fetal injury and preterm birth

Lipid analogs reveal features critical for hemolysis and diminish granadaene mediated Group B Streptococcus infection

Although certain microbial lipids are toxins, the structural features important for cytotoxicity remain unknown. Increased functional understanding is essential for developing therapeutics against toxic microbial lipids. Group B Streptococci (GBS) are bacteria associated with preterm births, stillbirths, and severe infections in neonates and adults. GBS produce a pigmented, cytotoxic lipid, known as granadaene. Despite its importance to all manifestations of GBS disease, studies towards understanding granadaene’s toxic activity are hindered by its instability and insolubility in purified form. Here, we report the synthesis and screening of lipid derivatives inspired by granadaene, which reveal features central to toxin function, namely the polyene chain length. Furthermore, we show that vaccination with a non-toxic synthetic analog confers the production of antibodies that inhibit granadaene-mediated hemolysis ex vivo and diminish GBS infection in vivo. This work provides unique structural and functional insight into granadaene and a strategy to mitigate GBS infection, which will be relevant to other toxic lipids encoded by human pathogens.This work was supported by funding from the National Institutes of Health Grants R01AI112619, R01AI133976, R01AI100989, and R21AI125907 and seed funds from Seattle Childrens Research Institute to L.

Observations of coincident EMIC wave activity and dusk-side energetic electron precipitation on 18-19 January 2013

Electromagnetic ion cyclotron (EMIC) waves have been suggested to be a cause of radiation belt electron loss to the atmosphere. Here simultaneous, magnetically conjugate measurements are presented of EMIC wave activity, measured at geosynchronous orbit and on the ground, and energetic electron precipitation, seen by the BARREL balloon campaign, on two consecutive days in January 2013. Multiple bursts of precipitation were observed on the dusk-side of the magnetosphere at the end of 18 Jan and again late on 19 Jan, concurrent with particle injections, substorm activity, and enhanced magnetospheric convection. The structure, timing, and spatial extent of the waves are compared to those of the precipitation during both days to determine when and where EMIC waves cause radiation belt electron precipitation. The conjugate measurements presented here provide observational support of the theoretical picture of dusk-side interaction of EMIC waves and MeV electrons leading to radiation belt loss

Sulfate deposition in subsurface regolith in Gusev crater, Mars

Excavating into the shallow Martian subsurface has the potential to expose stratigraphic layers and mature regolith, which may hold a record of more ancient aqueous interactions than those expected under current Martian surface conditions. During the Spirit rover’s exploration of Gusev crater, rover wheels were used to dig three trenches into the subsurface regolith down to 6–11 cm depth: Road Cut, the Big Hole, and The Boroughs. A high oxidation state of Fe and high concentrations of Mg, S, Cl, and Br were found in the subsurface regolith within the two trenches on the plains, between the Bonneville crater and the foot of Columbia Hills. Data analyses on the basis of geochemistry and mineralogy observations suggest the deposition of sulfate minerals within the subsurface regolith, mainly Mg-sulfates accompanied by minor Ca-sulfates and perhaps Fe-sulfates. An increase of Fe2O3, an excess of SiO2, and a minor decrease in the olivine proportion relative to surface materials are also inferred. Three hypotheses are proposed to explain the geochemical trends observed in trenches: (1) multiple episodes of acidic fluid infiltration, accompanied by in situ interaction with igneous minerals and salt deposition; (2) an open hydrologic system characterized by ion transportation in the fluid, subsequent evaporation of the fluid, and salt deposition; and (3) emplacement and mixing of impact ejecta of variable composition. While all three may have plausibly contributed to the current state of the subsurface regolith, the geochemical data are most consistent with ion transportation by fluids and salt deposition as a result of open-system hydrologic behavior. Although sulfates make up >20 wt.% of the regolith in the wall of The Boroughs trench, a higher hydrated sulfate than kieserite within The Boroughs or a greater abundance of sulfates elsewhere than is seen in The Boroughs wall regolith would be needed to hold the structural water indicated by the water-equivalent hydrogen concentration observed by the Gamma-Ray Spectrometer on Odyssey in the Gusev region

Supervolcanoes Within an Ancient Volcanic Province in Arabia Terra, Mars

Several irregularly shaped craters located within Arabia Terra, Mars represent a new type of highland volcanic construct and together constitute a previously unrecognized martian igneous province. Similar to terrestrial supervolcanoes, these low-relief paterae display a range of geomorphic features related to structural collapse, effusive volcanism, and explosive eruptions. Extruded lavas contributed to the formation of enigmatic highland ridged plains in Arabia Terra. Outgassed sulfur and erupted fine-grained pyroclastics from these calderas likely fed the formation of altered, layered sedimentary rocks and fretted terrain found throughout the equatorial region. Discovery of a new type of volcanic construct in the Arabia volcanic province fundamentally changes the picture of ancient volcanism and climate evolution on Mars. Other eroded topographic basins in the ancient Martian highlands that have been dismissed as degraded impact craters should be reconsidered as possible volcanic constructs formed in an early phase of widespread, disseminated magmatism on Mars