Planck 2013 results. XXVII. Doppler boosting of the CMB : Eppur si muove

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Conserved Mosquito/Parasite Interactions Affect Development of Plasmodium falciparum in Africa

In much of sub-Saharan Africa, the mosquito Anopheles gambiae is the main vector of the major human malaria parasite, Plasmodium falciparum. Convenient laboratory studies have identified mosquito genes that affect positively or negatively the developmental cycle of the model rodent parasite, P. berghei. Here, we use transcription profiling and reverse genetics to explore whether five disparate mosquito gene regulators of P. berghei development are also pertinent to A. gambiae/P. falciparum interactions in semi-natural conditions, using field isolates of this parasite and geographically related mosquitoes. We detected broadly similar albeit not identical transcriptional responses of these genes to the two parasite species. Gene silencing established that two genes affect similarly both parasites: infections are hindered by the intracellular local activator of actin cytoskeleton dynamics, WASP, but promoted by the hemolymph lipid transporter, ApoII/I. Since P. berghei is not a natural parasite of A. gambiae, these data suggest that the effects of these genes have not been drastically altered by constant interaction and co-evolution of A. gambiae and P. falciparum; this conclusion allowed us to investigate further the mode of action of these two genes in the laboratory model system using a suite of genetic tools and infection assays. We showed that both genes act at the level of midgut invasion during the parasite's developmental transition from ookinete to oocyst. ApoII/I also affects the early stages of oocyst development. These are the first mosquito genes whose significant effects on P. falciparum field isolates have been established by direct experimentation. Importantly, they validate for semi-field human malaria transmission the concept of parasite antagonists and agonists

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations

Planck 2013 results. XXI. Power spectrum and high-order statistics of the Planck all-sky Compton parameter map

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Planck 2013 results. XVI. Cosmological parameters

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Polymorphisms in Anopheles gambiae Immune Genes Associated with Natural Resistance to Plasmodium falciparum

Many genes involved in the immune response of Anopheles gambiae, the main malaria vector in Africa, have been identified, but whether naturally occurring polymorphisms in these genes underlie variation in resistance to the human malaria parasite, Plasmodium falciparum, is currently unknown. Here we carried out a candidate gene association study to identify single nucleotide polymorphisms (SNPs) associated with natural resistance to P. falciparum. A. gambiae M form mosquitoes from Cameroon were experimentally challenged with three local wild P. falciparum isolates. Statistical associations were assessed between 157 SNPs selected from a set of 67 A. gambiae immune-related genes and the level of infection. Isolate-specific associations were accounted for by including the effect of the isolate in the analysis. Five SNPs were significantly associated to the infection phenotype, located within or upstream of AgMDL1, CEC1, Sp PPO activate, Sp SNAKElike, and TOLL6. Low overall and local linkage disequilibrium indicated high specificity in the loci found. Association between infection phenotype and two SNPs was isolate-specific, providing the first evidence of vector genotype by parasite isolate interactions at the molecular level. Four SNPs were associated to either oocyst presence or load, indicating that the genetic basis of infection prevalence and intensity may differ. The validity of the approach was verified by confirming the functional role of Sp SNAKElike in gene silencing assays. These results strongly support the role of genetic variation within or near these five A. gambiae immune genes, in concert with other genes, in natural resistance to P. falciparum. They emphasize the need to distinguish between infection prevalence and intensity and to account for the genetic specificity of vector-parasite interactions in dissecting the genetic basis of Anopheles resistance to human malaria

Planck 2013 results. XVII. Gravitational lensing by large-scale structure

On the arcminute angular scales probed by Planck, the cosmic microwave background (CMB) anisotropies are gently perturbed by gravitational lensing. Here we present a detailed study of this effect, detecting lensing independently in the 100, 143, and 217 GHz frequency bands with an overall significance of greater than 25σ. We use thetemperature-gradient correlations induced by lensing to reconstruct a (noisy) map of the CMB lensing potential, which provides an integrated measure of the mass distribution back to the CMB last-scattering surface. Our lensing potential map is significantly correlated with other tracers of mass, a fact which we demonstrate using several representative tracers of large-scale structure. We estimate the power spectrum of the lensing potential, finding generally good agreement with expectations from the best-fitting ΛCDM model for the Planck temperature power spectrum, showing that this measurement at z = 1100 correctly predicts the properties of the lower-redshift, later-time structures which source the lensing potential. When combined with the temperature power spectrum, our measurement provides degeneracy-breaking power for parameter constraints; it improves CMB-alone constraints on curvature by a factor of two and also partly breaks the degeneracy between the amplitude of the primordial perturbation power spectrum and the optical depth to reionization, allowing a measurement of the optical depth to reionization which is independent of large-scale polarization data. Discarding scale information, our measurement corresponds to a 4% constraint on the amplitude of the lensing potential power spectrum, or a 2% constraint on the root-mean-squared amplitude of matter fluctuations at z ~ 2

Planck 2013 results. XII. Diffuse component separation

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