Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite

Assigning function to orphan membrane transport proteins and prioritizing candidates for detailed biochemical characterization remain fundamental challenges and are particularly important for medically relevant pathogens, such as malaria parasites. Here we present a comprehensive genetic analysis of 35 orphan transport proteins of Plasmodium berghei during its life cycle in mice and Anopheles mosquitoes. Six genes, including four candidate aminophospholipid transporters, are refractory to gene deletion, indicative of essential functions. We generate and phenotypically characterize 29 mutant strains with deletions of individual transporter genes. Whereas seven genes appear to be dispensable under the experimental conditions tested, deletion of any of the 22 other genes leads to specific defects in life cycle progression in vivo and/or host transition. Our study provides growing support for a potential link between heavy metal homeostasis and host switching and reveals potential targets for rational design of new intervention strategies against malaria

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 CuTP demonstrated that CuTP is predominantly located in vesicular bodies of the parasite. A P. berghei loss-of-function mutant line was readily obtained and showed no apparent defect in in vivo blood stage growth. Parasite transmission through the mosquito vector was severely affected, but not entirely abolished. We show that male and female gametocytes are abundant in cutp− parasites, but activation of male microgametes and exflagellation were strongly impaired. This specific defect could be mimicked by addition of the copper chelator neocuproine to wild-type gametocytes. A cross-fertilization assay demonstrated that female fertility was also severely abrogated. In conclusion, we provide experimental genetic and pharmacological evidence that a healthy copper homeostasis is critical to malaria parasite fertility of both genders of gametocyte and, hence, to transmission to the mosquito vector

Exposure damage mechanisms for KCl windows in high power laser systems

An experimental study of the 10.6 micrometer and 0.6328 micrometer optical properties of single crystal and europium doped polycrystal is described. Significant variations in the optical properties are observed over periods of exposure up to 100 hours. Models are proposed to predict the 10.6 micrometer absorptivity for long exposure periods. Mechanical creep has been detected in both materials at high temperature

The effects of dust evolution on disks in the mid-IR

In this paper, we couple together the dust evolution code two-pop-py with the thermochemical disk modelling code ProDiMo. We create a series of thermochemical disk models that simulate the evolution of dust over time from 0.018 Myr to 10 Myr, including the radial drift, growth, and settling of dust grains. We examine the effects of this dust evolution on the mid-infrared gas emission, focussing on the mid-infrared spectral lines of C2H2, CO2, HCN, NH3, OH, and H2O that are readily observable with Spitzer and the upcoming E-ELT and JWST. The addition of dust evolution acts to increase line fluxes by reducing the population of small dust grains. We find that the spectral lines of all species except C2H2 respond strongly to dust evolution, with line fluxes increasing by more than an order of magnitude across the model series as the density of small dust grains decreases over time. The C2H2 line fluxes are extremely low due to a lack of abundance in the infrared line-emitting regions, despite C2H2 being commonly detected with Spitzer, suggesting that warm chemistry in the inner disk may need further investigation. Finally, we find that the CO2 flux densities increase more rapidly than the other species as the dust disk evolves. This suggests that the flux ratios of CO2 to other species may be lower in disks with less-evolved dust populations.Comment: 13 pages, 9 figures, accepted in A&

On the predictions and limitations of the BeckerDoring model for reaction kinetics in micellar surfactant solutions

We investigate the breakdown of a system of micellar aggregates in a surfactant solution following an order-one dilution. We derive a mathematical model based on the Becker–Döring system of equations, using realistic expressions for the reaction constants fit to Molecular Dynamics simulations. We exploit the largeness of typical aggregation numbers to derive a continuum model, substituting a large system of ordinary differential equations for a partial differential equation in two independent variables: time and aggregate size. Numerical solutions demonstrate that re-equilibration occurs in two distinct stages over well-separated time-scales, in agreement with experiment and with previous theories. We conclude by exposing a limitation in the Becker–Döring theory for re-equilibration and discuss potential resolutions

An asymptotic theory for the re-equilibration of a micellar surfactant solution

Micellar surfactant solutions are characterized by a distribution of aggregates comprised predominantly of pre-micellar aggregates (monomers, dimers, trimers, etc.) and a region of proper micelles close to the peak aggregation number, connected by an intermediate region containing a very low concentration of aggregates. Such a distribution gives rise to a distinct two-timescale re-equilibration following a system dilution, known as the 1 and 2 processes, whose dynamics may be described by the Becker–Döring equations. We use a continuum version of these equations to develop a reduced asymptotic description that elucidates the behavior during each of these processes

Development of a stratospheric and mesospheric microwave temperature sounder experiment

A passive microwave spectrometer system for measuring global atmospheric temperature profiles from 0-75 km altitude was developed and analyzed. The system utilizes 12 channels near the 5 mm wavelength oxygen absorption band and is designed to provide global coverage by scanning perpendicular to the orbital track of a polar orbiting satellite. A significant improvement in the accuracy of theoretical atmospheric microwave transmittance functions was achieved through the development of a first-order approximation to overlapping line theory for the oxygen molecule. This approximation is particularly important in the troposphere and lower stratosphere where pressure-broadening blends nearby lines. Ground-based and aircraft observations of several resonances of stratospheric oxygen generally support the theory. The 23, 25, 29, and 31 atmospheric oxygen lines were measured and the frequencies of several such oxygen lines were measured with improved precision. The polarization and Zeeman splitting of the atmospheric 27 line was also observed

Resolving the compact dusty discs around binary post-AGB stars using N-band interferometry

We present the first mid-IR long baseline interferometric observations of the circumstellar matter around binary post-AGB stars. Two objects, SX Cen and HD 52961, were observed using the VLTI/MIDI instrument during Science Demonstration Time. Both objects are known binaries for which a stable circumbinary disc is proposed to explain the SED characteristics. This is corroborated by our N-band spectrum showing a crystallinity fraction of more than 50 % for both objects, pointing to a stable environment where dust processing can occur. Surprisingly, the dust surrounding SX Cen is not resolved in the interferometric observations providing an upper limit of 11 mas (or 18 AU at the distance of this object) on the diameter of the dust emission. This confirms the very compact nature of its circumstellar environment. The dust emission around HD 52961 originates from a very small but resolved region, estimated to be ~ 35 mas at 8 micron and ~ 55 mas at 13 micron. These results confirm the disc interpretation of the SED of both stars. In HD 52961, the dust is not homogeneous in its chemical composition: the crystallinity is clearly concentrated in the hotter inner region. Whether this is a result of the formation process of the disc, or due to annealing during the long storage time in the disc is not clear.Comment: 12 pages, 10 figures, accepted for publication in A &

CO ro-vibrational lines in HD100546: A search for disc asymmetries and the role of fluorescence

We have studied the emission of CO ro-vibrational lines in the disc around the Herbig Be star HD100546 with the final goal of using these lines as a diagnostic to understand inner disc structure in the context of planet formation. High-resolution IR spectra of CO ro-vibrational emission at eight different position angles were taken with CRIRES at the VLT. From these spectra flux tables, CO ro-vibrational line profiles, and population diagrams were produced. We have investigated variations in the line profile shapes and line strengths as a function of slit position angle. We used the thermochemical disc modelling code ProDiMo based on the chemistry, radiation field, and temperature structure of a previously published model for HD100546. Comparing observations and the model, we investigated the possibility of disc asymmetries, the excitation mechanism (UV fluorescence), the geometry, and physical conditions of the inner disc. The observed CO ro-vibrational lines are largely emitted from the inner rim of the outer disc at 10-13 AU. The line shapes are similar for all v levels and line fluxes from all vibrational levels vary only within one order of magnitude. All line profile asymmetries and variations can be explained with a symmetric disc model to which a slit correction and pointing offset is applied. Because the angular size of the CO emitting region (10-13 AU) and the slit width are comparable the line profiles are very sensitive to the placing of the slit. The model reproduces the line shapes and the fluxes of the v=1-0 lines as well as the spatial extent of the CO ro-vibrational emission. It does not reproduce the observed band ratios of 0.5-0.2 with higher vibrational bands. We find that lower gas volume densities at the surface of the inner rim of the outer disc can make the fluorescence pumping more effcient and reproduce the observed band ratios.Comment: 20 pages, 21 figure