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Background: Genome-wide association studies have identified ATP2B4 as a severe malaria resistance gene. Recently, 8 potential causal regulatory variants have been shown to be associated with severe malaria. Methods: Genotyping of rs10900585, rs11240734, rs1541252, rs1541253, rs1541254, rs1541255, rs10751450, rs10751451 and rs10751452 was performed in 154 unrelated individuals (79 controls and 75 mild malaria patients). rs10751450, rs10751451 and rs10751452 were genotyped by Taqman assays, whereas the fragment of the ATP2B4 gene containing the remaining SNPs was sequenced. Logistic regression analysis was used to assess the association between the SNPs and mild malaria. Results: The results showed that mild malaria was associated with rs10900585, rs11240734, rs1541252, rs1541253, rs1541254, rs1541255, rs10751450, rs10751451 and rs10751452. The homozygous genotypes for the major alleles were associated with an increased risk of mild malaria. Furthermore, the haplotype containing the major alleles and that containing the minor alleles were the most frequent haplotypes. Individuals with the major haplotypes had a significantly higher risk of mild malaria compared to the carriers of the minor allele haplotype. Conclusions: ATP2B4 polymorphisms that have been associated with severe malaria are also associated with mild malaria. [ABSTRACT FROM AUTHOR]

Genome-wide association studies for severe malaria (SM) have identified 30 genetic variants mostly located in non-coding regions. Here, we aimed to identify potential causal genetic variants located in these loci and demonstrate their functional activity. We systematically investigated the regulatory effect of the SNPs in linkage disequilibrium (LD) with the malaria-associated genetic variants. Annotating and prioritizing genetic variants led to the identification of a regulatory region containing five ATP2B4 SNPs in LD with rs10900585. We found significant associations between SM and rs10900585 and our candidate SNPs (rs11240734, rs1541252, rs1541253, rs1541254, and rs1541255) in a Senegalese population. Then, we demonstrated that both individual SNPs and the combination of SNPs had regulatory effects. Moreover, CRISPR/Cas9-mediated deletion of this region decreased ATP2B4 transcript and protein levels and increased Ca2+ intracellular concentration in the K562 cell line. Our data demonstrate that severe malaria-associated genetic variants alter the expression of ATP2B4 encoding a plasma membrane calcium-transporting ATPase 4 (PMCA4) expressed on red blood cells. Altering the activity of this regulatory element affects the risk of SM, likely through calcium concentration effect on parasitaemia. [ABSTRACT FROM AUTHOR]

The ozone decomposition onto mineral surfaces prepared with traces of solid TiO2 in a matrix of SiO2 in order to mimic mineral dust particles has been investigated using a coated- wall flow-tube system at room temperature and atmospheric pressure. The ozone uptake coefficients were measured both under dark conditions and irradiation using near UV-light. While uptake in the dark was negligible, a large photoenhanced ozone uptake was observed. For TiO2/SiO2 mixtures under irradiation, the uptake coefficients increased with increasing TiO2 mass fraction (from 1 to 3 wt %), and the corresponding uptake coefficient based on the geometric surfaces ranged from 3 × 10-5 to 3 × 10-5. The uptake kinetics was also observed to increase with decreasing ozone concentration between 290 and 50 ppbv. Relative humidity influenced the ozone uptake on the film, and a reduced ozone loss was observed for relative humidity above 30%. The experimental results suggest that under atmospherically relevant conditions the photo-chemistry of dust can represent an important sink of ozone inside the dust plume. [ABSTRACT FROM AUTHOR]

We studied the lateral forces arising during the vertical indentation of the cell membrane by an optically trapped microbead, using back focal plane interferometry to determine force components in all directions. We analyzed the cell-microbead interaction and showed that indeed the force had also lateral components. Using the Hertz model, we calculated and compared the elastic moduli resulting from the total and vertical forces, showing that the differences are important and the total force should be considered. To confirm our results we analyzed cells from two breast cancer cell lines: MDA-MB-231 and HBL-100, known to have different cancer aggressiveness and hence stiffness. [ABSTRACT FROM PUBLISHER]

Abstract: In this study, we evaluated the capability of different datasets for soil drainage mapping within agricultural fields. The evaluated datasets include apparent soil electrical conductivity (ECa), remotely sensed high-resolution airborne hyperspectral reflectance (HR) and C-band synthetic aperture radar (SAR) backscattering coefficients, and a high precision digital elevation model (DEM) generated from GPS measurements. The study site was located in an experimental farm in Ottawa, Ontario, Canada. Three drainage classes representing moderately well drained, imperfectly drained, and poorly drained soils were identified during field surveys according to soil surveyor expert knowledge. Variables that significantly contributed to soil drainage classification were selected from the evaluated datasets with a stepwise discriminant analysis procedure. The selected variables were then used to classify soil drainage with a maximum likelihood classifier. A substantial agreement between the observed and classified drainage classes was achieved using the HR dataset, with a kappa coefficient (κ) of 0.68. Moderate agreement was achieved using the SAR and the ECa datasets, with κ =0.52 and 0.55, respectively. The result obtained using the DEM-derived topographic variables showed only a fair agreement (κ =0.31). Canonical analysis was also conducted to investigate the association between these datasets and field-observed soil water regime descriptors. This potentially provides an alternative way of drainage mapping using canonical variate. The canonical correlation between the water regime descriptors and the evaluated datasets was 0.81, 0.75 and 0.83 for the HR, SAR and soil ECa datasets, respectively. In this study, the topographic variables were not as efficient, but when combined with the SAR and soil ECa datasets, they improved soil drainage mapping. [Copyright &y& Elsevier]