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

An examination of the molecular mechanisms controlling the tissue accumulation of conjugated linoleic acid (CLA) in cattle

End of project reportLong chain n-3 polyunsaturated fatty acids (n-3 PUFA) and conjugated linoleic acid (CLA) have demonstrable and potential human health benefits in terms of preventing cancer, diabetes, chronic inflammation, obesity and coronary heart disease. Supplementation of cattle diets with a blend of oils rich in n-3 PUFA and linoleic acid have a synergistic effect on the accumulation of ruminal and tissue concentrations of trans vaccenic acid (TVA), the main substrate for ?-9 desaturase which is responsible for de novo tissue synthesis of the cis 9, trans 11 isomer of CLA. This dietary strategy translates into increases in milk concentrations of CLA in dairy cows; however, concentrations in the muscle of beef animals have not always been increased. There is an apparent paradox in that n-3 PUFA supplementation enhances ruminal synthesis of trans-vaccenic acid (TVA), but then inhibits its conversion to CLA possibly through altering the activity of ?-9 desaturase. Recently, the promoter regions of the bovine ?- 9 desaturase gene has been isolated and analysed and has been shown to contain a conserved PUFA response region

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

The Thermal Structure of the Circumstellar Disk Surrounding the Classical Be Star gamma Cassiopeia

We have computed radiative equilibrium models for the gas in the circumstellar envelope surrounding the hot, classical Be star $\gamma$Cassiopeia. This calculation is performed using a code that incorporates a number of improvements over previous treatments of the disk's thermal structure by \citet{mil98} and \citet{jon04}; most importantly, heating and cooling rates are computed with atomic models for H, He, CNO, Mg, Si, Ca, & Fe and their relevant ions. Thus, for the first time, the thermal structure of a Be disk is computed for a gas with a solar chemical composition as opposed to assuming a pure hydrogen envelope. We compare the predicted average disk temperature, the total energy loss in H$\alpha$, and the near-IR excess with observations and find that all can be accounted for by a disk that is in vertical hydrostatic equilibrium with a density in the equatorial plane of $\rho(R)\approx 3$ to $5\cdot 10^{-11} (R/R_*)^{-2.5} \rm g cm^{-3}$. We also discuss the changes in the disk's thermal structure that result from the additional heating and cooling processes available to a gas with a solar chemical composition over those available to a pure hydrogen plasma.Comment: 11 pages, 8 figures high resolution figures available at http://inverse.astro.uwo.ca/sig_jon07.htm

Investigating students seriousness during selected conceptual inventory surveys

Conceptual inventory surveys are routinely used in education research to identify student learning needs and assess instructional practices. Students might not fully engage with these instruments because of the low stakes attached to them. This paper explores tests that can be used to estimate the percentage of students in a population who might not have taken such surveys seriously. These three seriousness tests are the pattern recognition test, the easy questions test, and the uncommon answers test. These three tests are applied to sets of students who were assessed either by the Force Concept Inventory, the Conceptual Survey of Electricity and Magnetism, or the Brief Electricity and Magnetism Assessment. The results of our investigation are compared to computer simulated populations of random answers.Comment: 8 pages; submitted to Phys Rev PE

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

Global gene expression in endometrium of high and low fertility heifers during the mid-luteal phase of the estrous cycle

peer-reviewedBackground In both beef and dairy cattle, the majority of early embryo loss occurs within the first 14 days following insemination. During this time-period, embryos are completely dependent on their maternal uterine environment for development, growth and ultimately survival, therefore an optimum uterine environment is critical to their survival. The objective of this study was to investigate whether differences in endometrial gene expression during the mid-luteal phase of the estrous cycle exist between crossbred beef heifers ranked as either high (HF) or low fertility (LF) (following four rounds of artificial insemination (AI)) using the Affymetrix® 23 K Bovine Gene Chip. Results Conception rates for each of the four rounds of AI were within a normal range: 70–73.3%. Microarray analysis of endometrial tissue collected on day 7 of the estrous cycle detected 419 differentially expressed genes (DEG) between HF (n = 6) and LF (n = 6) animals. The main gene pathways affected were, cellular growth and proliferation, angiogenesis, lipid metabolism, cellular and tissue morphology and development, inflammation and metabolic exchange. DEG included, FST, SLC45A2, MMP19, FADS1 and GALNT6. Conclusions This study highlights, some of the molecular mechanisms potentially controlling uterine endometrial function during the mid-luteal phase of the estrous cycle, which may contribute to uterine endometrial mediated impaired fertility in cattle. Differentially expressed genes are potential candidate genes for the identification of genetic variation influencing cow fertility, which may be incorporated into future breeding programmes.Teagasc Walsh Fellowship Programm

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&