Visualizing,quantifying, and manipulating mitochondrial DNA in vivo

Mitochondrial DNA (mtDNA) encodes proteins and RNAs that support the functions of mitochondria and thereby numerous physiological processes. Mutations of mtDNA can cause mitochondrial diseases and are implicated in aging. The mtDNA within cells is organized into nucleoids within the mitochondrial matrix, but how mtDNA nucleoids are formed and regulated within cells remains incompletely resolved. Visualization of mtDNA within cells is a powerful means by which mechanistic insight can be gained. Manipulation of the amount and sequence of mtDNA within cells is important experimentally and for developing therapeutic interventions to treat mitochondrial disease. This review details recent developments and opportunities for improvements in the experimental tools and techniques that can be used to visualize, quantify, and manipulate the properties of mtDNA within cells.     

The calculation of structural,elastic and phase stability properties of minerals using first principles techniques: A comparison of HF,DFT and Hybrid functional treatments of exchange and correlation

We benchmark the performance of four treatments of electron exchange and correlation in the prediction of structural and elastic properties of a range of minerals. The treatments used are the Hartree-Fock (HF) theory, the local density approximation (LDA) and the generalised gradient approximation (GGA) to the density functional theory (DFT) and Becke's three parameter hybrid functional (B3LYP). We find that the hybrid functional, B3LYP method yields computed elastic properties in significantly better agreement to experiment than HF or DFT-LDA and performs at least as well, if not better than the most successful DFT-GGA functionals. We suggest that B3LYP is a simple, reliable and computationally efficient tool for the ab initio simulation of mineral systems.     

Editorial

Abstract

Grand canonical molecular dynamics (GCMD) simulations are used to study the adsorption and desorption of Lennard-Jones nitrogen in three slit pore junction models of microporous graphite. These networks consist of two narrow pores separated by a wider (cavity) pore. We report results for cases where the narrow pore has a width of only two or three molecular diameters. Using the GCMD technique, a novel freezing transition is observed which results in pore blocking in the narrow pores of the network, which are less than 1 nm wide. This freezing results from the adsorption energy barrier at the junction between the narrow and wider pores. This type of pore blocking could account for the apparent increase in pore volume with increasing temperature that has been experimentally observed in microporous graphite systems. For networks in which the narrower pores are somewhat larger, with a width of 1.28 nm, this pore blocking effect is much reduced, and adsorbate molecules enter and fill the central cavity. In such cases, however, desorption is incomplete, some residual adsorbate remaining in the central cavity even at the lowest pressures.     

Roma women in Athenian firms: do they face wage bias?

In the current study, we analyse the effect of having a Roma background on women's wages. By utilizing data from sixteen multiethnic municipalities in which Roma live, we estimate that 66.2 per cent of the wage differential between Roma and non-Roma female workers cannot be explained by differences in observed characteristics. Prejudices against Roma women are discussed and appear to explain the wage gap found here. The occupational segregation of the Roma in low-paid jobs and employers' statistical motivations are also found to influence wages earned by Roma. This study concludes that there is a need for better implementation of existing laws, rules and regulations, which would counter the discrimination against minority women in the labour market. In addition, a better means of assessing workers' skills might contribute to the reduction of wage discrimination, and greater educational achievement would significantly boost the economic status of Roma women.     

Mechanism of Ferrous Iron Binding and Oxidation by Ferritin from a Pennate Diatom

A novel ferritin was recently found in Pseudo-nitzschia multiseries (PmFTN), a marine pennate diatom that plays a major role in global primary production and carbon sequestration into the deep ocean. Crystals of recombinant PmFTN were soaked in iron and zinc solutions, and the structures were solved to 1.65–2.2-Å resolution. Three distinct iron binding sites were identified as determined from anomalous dispersion data from aerobically grown ferrous soaked crystals. Sites A and B comprise the conserved ferroxidase active site, and site C forms a pathway leading toward the central cavity where iron storage occurs. In contrast, crystal structures derived from anaerobically grown and ferrous soaked crystals revealed only one ferrous iron in the active site occupying site A. In the presence of dioxygen, zinc is observed bound to all three sites. Iron oxidation experiments using stopped-flow absorbance spectroscopy revealed an extremely rapid phase corresponding to Fe(II) oxidation at the ferroxidase site, which is saturated after adding 48 ferrous iron to apo-PmFTN (two ferrous iron per subunit), and a much slower phase due to iron core formation. These results suggest an ordered stepwise binding of ferrous iron and dioxygen to the ferroxidase site in preparation for catalysis and a partial mobilization of iron from the site following oxidation.     

Inferring Admixture Histories of Human Populations Using Linkage Disequilibrium

Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese.     

Grazers: biocatalysts of terrestrial silica cycling

Silica is well known for its role as inducible defence mechanism countering herbivore attack, mainly through precipitation of opaline, biogenic silica (BSi) bodies (phytoliths) in plant epidermal tissues. Even though grazing strongly interacts with other element cycles, its impact on terrestrial silica cycling has never been thoroughly considered. Here, BSi content of ingested grass, hay and faeces of large herbivores was quantified by performing multiple chemical extraction procedures for BSi, allowing the assessment of chemical reactivity. Dissolution experiments with grass and faeces were carried out to measure direct availability of BSi for dissolution. Average BSi and readily soluble silica numbers were higher in faeces as compared with grass or hay, and differences between herbivores could be related to distinct digestive strategies. Reactivity and dissolvability of BSi increases after digestion, mainly due to degradation of organic matrices, resulting in higher silica turnover rates and mobilization potential from terrestrial to aquatic ecosystems in non-grazed versus grazed pasture systems (2 versus 20 kg Si ha⁻¹ y⁻¹). Our results suggest a crucial yet currently unexplored role of herbivores in determining silica export from land to ocean, where its availability is linked to eutrophication events and carbon sequestration through C–Si diatom interactions.