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Several lines of evidence link glucose-6-phosphate dehydrogenase (G6PD) deficiency to protection from severe malaria. Early reports suggested most G6PD deficiency in sub-Saharan Africa was because of the 202A/376G G6PD AÀ allele, and recent association studies of G6PD deficiency have employed genotyping as a convenient way to determine enzyme status. However, further work has suggested that other G6PD deficiency alleles are relatively common in some regions of West Africa. To investigate the consequences of unrecognized allelic heterogeneity on association studies, in particular studies of G6PD deficiency and malaria, we carried out a case-control analysis of 2488 Gambian children with severe malaria and 3875 controls. No significant association was found between severe malaria and the 202A/376G G6PD AÀ allele when analyzed alone, but pooling 202A/376G with other deficiency alleles revealed the signal of protection (male odds ratio (OR) 0.77, 95% CI 0.62 -0.95, P ¼ 0.016; female OR 0.71, 95% CI 0.56 -0.89, P ¼ 0.004). We have identified the 968C mutation as the most common G6PD AÀ allele in The Gambia. Our results highlight some of the consequences of allelic heterogeneity, particularly the increased type I error. They also suggest that G6PD-deficient male hemizygotes and female heterozygotes are protected from severe malaria.

There is growing epidemiological and molecular evidence that ABO blood group affects host susceptibility to severe Plasmodium falciparum infection. The high frequency of common ABO alleles means that even modest differences in susceptibility could have a significant impact on the health of people living in malaria endemic regions. We performed an association study, the first to utilize key molecular genetic variation underlying the ABO system, genotyping >9000 individuals across three African populations. Using population- and family-based tests, we demonstrated that alleles producing functional ABO enzymes are associated with greater risk of severe malaria phenotypes (particularly malarial anemia) in comparison with the frameshift deletion underlying blood group O: case-control allelic odds ratio (OR), 1.2; 95% confidence interval (CI), 1.09-1.32; P = 0.0003; family-studies allelic OR, 1.19; 95% CI, 1.08-1.32; P = 0.001; pooled across all studies allelic OR, 1.18; 95% CI, 1.11-1.26; P = 2 x 10(-7). We found suggestive evidence of a parent-of-origin effect at the ABO locus by analyzing the family trios. Non-O haplotypes inherited from mothers, but not fathers, are significantly associated with severe malaria (likelihood ratio test of Weinberg, P = 0.046). Finally, we used HapMap data to demonstrate a region of low F(ST) (-0.001) between the three main HapMap population groups across the ABO locus, an outlier in the empirical distribution of F(ST) across chromosome 9 (approximately 99.5-99.9th centile). This low F(ST) region may be a signal of long-standing balancing selection at the ABO locus, caused by multiple infectious pathogens including P. falciparum.

Biomineralization plays a fundamental role in the global silicon cycle. Grasses are known to mobilize significant quantities of Si in the form of silica biominerals and dominate the terrestrial realm today, but they have relatively recent origins and only rose to taxonomic and ecological prominence within the Cenozoic Era. This raises questions regarding when and how the biological silica cycle evolved. To address these questions, we examined silica abundances of extant members of early-diverging land plant clades, which show that silica biomineralization is widespread across terrestrial plant linages. Particularly high silica abundances are observed in lycophytes and early-diverging ferns. However, silica biomineralization is rare within later-evolving gymnosperms, implying a complex evolutionary history within the seed plants. Electron microscopy and X-ray spectroscopy show that the most common silica-mineralized tissues include the vascular system, epidermal cells, and stomata, which is consistent with the hypothesis that biomineralization in plants is frequently coupled to transpiration. Furthermore, sequence, phylogenetic, and structural analysis of nodulin 26-like intrinsic proteins from diverse plant genomes points to a plastic and ancient capacity for silica accumulation within terrestrial plants. The integration of these two comparative biology approaches demonstrates that silica biomineralization has been an important process for land plants over the course of their >400 My evolutionary history.phytolith | fern | lycophyte | silicon | aquaporin I n modern ecosystems, land plants play a major role in the silica cycle through the accumulation and synthesis of amorphous biominerals composed of SiO 2 , known as phytoliths or silica bodies. It is widely appreciated that actively accumulating plants such as grasses are important components of the terrestrial biological pump of silica (1-3). Plant silica also plays a key role in connecting the terrestrial and marine carbon cycles, because silica is an important nutrient for marine silica-biomineralizing primary producers (i.e., diatoms) (1, 2, 4-7). However, both grasses and diatoms evolved in the latter part of the Mesozoic Era (8-10) and rose to ecological dominance within the Cenozoic Era (6,9,(11)(12)(13)(14). Determining precisely when and how the terrestrial-marine silica teleconnections evolved remains an obstacle to reconstructing the history of the silica cycle.Direct analysis of silica bodies in the fossil record provides limited insight into this problem. When fossiliferous material is macerated, it is often challenging to identify whether residual silica bodies are the result of primary biomineralization or secondary diagenetic processes, and if a living plant origin is suspected, it is often difficult to assign taxonomic identity to the phytolith producer. In addition, with rare exceptions (e.g., ref.15), lagerstätten that preserve exceptional anatomical detail in fossils, and might therefore be expected to preserve silica bodies, tend to be over...

Contents 1333I.1334II.1335III.1339IV.1344V.1347VI.134713481348References1348 Summary The Carboniferous, the time of Earth's penultimate icehouse and widespread coal formation, was dominated by extinct lineages of early‐diverging vascular plants. Studies of nearest living relatives of key Carboniferous plants suggest that their physiologies and growth forms differed substantially from most types of modern vegetation, particularly forests. It remains a matter of debate precisely how differently and to what degree these long‐extinct plants influenced the environment. Integrating biophysical analysis of stomatal and vascular conductivity with geochemical analysis of fossilized tissues and process‐based ecosystem‐scale modeling yields a dynamic and unique perspective on these paleoforests. This integrated approach indicates that key Carboniferous plants were capable of growth and transpiration rates that approach values found in extant crown‐group angiosperms, differing greatly from comparatively modest rates found in their closest living relatives. Ecosystem modeling suggests that divergent stomatal conductance, leaf sizes and stem life span between dominant clades would have shifted the balance of soil–atmosphere water fluxes, and thus surface runoff flux, during repeated, climate‐driven, vegetation turnovers. This synthesis highlights the importance of ‘whole plant’ physiological reconstruction of extinct plants and the potential of vascular plants to have influenced the Earth system hundreds of millions of years ago through vegetation–climate feedbacks.

Aerobic exercise is a viable intervention for PD that can be protective against increased depressive symptoms, and can improve several non-motor domains, including executive dysfunction and related aspects of language production. (JINS, 2016, 22, 878-889).

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Medullosa stands apart from most Paleozoic seed plants in its combination of large leaf area, complex vascular structure, and extremely large water-conducting cells. To investigate the hydraulic consequences of these anatomical features and to compare them with other seed plants, we have adapted a model of water transport in xylem cells that accounts for resistance to flow from the lumen, pits, and pit membranes, and that can be used to compare extinct and extant plants in a quantitative way. Application of this model to Medullosa, the Paleozoic coniferophyte Cordaites, and the extant conifer Pinus shows that medullosan tracheids had the capacity to transport water at volume flow rates more comparable to those of angiosperm vessels than to those characteristic of ancient and modern coniferophyte tracheids. Tracheid structure in Medullosa, including the large pit membrane area per tracheid and the high ratio of tracheid diameter to wall thickness, suggests that its xylem cells operated at significant risk of embolism and implosion, making this plant unlikely to survive significant water stress These features further suggest that tracheids could not have furnished significant structural support, requiring either that other tissues supported these plants or that at least some medullosans were vines. In combination with high tracheid conductivity, distinctive anatomical characters of Medullosa such as the anomalous growth of vascular cambium and the large number of leaf traces that enter each petiole base suggest vascular adaptations to meet the evapotranspiration demands of its large leaves. The evolution of highly efficient conducting cells dictates a need to supply structural support via other tissues, both in tracheid-based stem seed plants and in vessel-bearing angiosperms.