Epistasis not needed to explain low dN/dS

An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a phenomenon known as epistasis. In a recent letter to Nature, Breen et al. (2012) argued that epistasis must be "pervasive throughout protein evolution" because the observed ratio between the per-site rates of non-synonymous and synonymous substitutions (dN/dS) is much lower than would be expected in the absence of epistasis. However, when calculating the expected dN/dS ratio in the absence of epistasis, Breen et al. assumed that all amino acids observed in a protein alignment at any particular position have equal fitness. Here, we relax this unrealistic assumption and show that any dN/dS value can in principle be achieved at a site, without epistasis. Furthermore, for all nuclear and chloroplast genes in the Breen et al. dataset, we show that the observed dN/dS values and the observed patterns of amino acid diversity at each site are jointly consistent with a non-epistatic model of protein evolution.Comment: This manuscript is in response to "Epistasis as the primary factor in molecular evolution" by Breen et al. Nature 490, 535-538 (2012

Large sulfur isotope fractionations in Martian sediments at Gale crater

Variability in the sulfur isotopic composition in sediments can reflect atmospheric, geologic and biological processes. Evidence for ancient fluvio-lacustrine environments at Gale crater on Mars and a lack of efficient crustal recycling mechanisms on the planet suggests a surface environment that was once warm enough to allow the presence of liquid water, at least for discrete periods of time, and implies a greenhouse effect that may have been influenced by sulfur-bearing volcanic gases. Here we report in situ analyses of the sulfur isotopic compositions of SO2 volatilized from ten sediment samples acquired by NASA’s Curiosity rover along a 13 km traverse of Gale crater. We find large variations in sulfur isotopic composition that exceed those measured for Martian meteorites and show both depletion and enrichment in 34S. Measured values of δ34S range from −47 ± 14‰ to 28 ± 7‰, similar to the range typical of terrestrial environments. Although limited geochronological constraints on the stratigraphy traversed by Curiosity are available, we propose that the observed sulfur isotopic signatures at Gale crater can be explained by equilibrium fractionation between sulfate and sulfide in an impact-driven hydrothermal system and atmospheric processing of sulfur-bearing gases during transient warm periods

Satellites and large doping- and temperature-dependence of electronic properties in hole-doped BaFe2As2

Over the last years, superconductivity has been discovered in several families of iron-based compounds. Despite intense research, even basic electronic properties of these materials, such as Fermi surfaces, effective electron masses, or orbital characters are still subject to debate. Here, we address an issue that has not been considered before, namely the consequences of dynamical screening of the Coulomb interactions among Fe-d electrons. We demonstrate its importance not only for correlation satellites seen in photoemission spectroscopy, but also for the low-energy electronic structure. From our analysis of the normal phase of BaFe2As2 emerges the picture of a strongly correlated compound with strongly doping- and temperature-dependent properties. In the hole overdoped regime, an incoherent metal is found, while Fermi-liquid behavior is recovered in the undoped compound. At optimal doping, the self-energy exhibits an unusual square-root energy dependence which leads to strong band renormalizations near the Fermi level

A realistic assessment of methods for extracting gene/protein interactions from free text

Background: The automated extraction of gene and/or protein interactions from the literature is one of the most important targets of biomedical text mining research. In this paper we present a realistic evaluation of gene/protein interaction mining relevant to potential non-specialist users. Hence we have specifically avoided methods that are complex to install or require reimplementation, and we coupled our chosen extraction methods with a state-of-the-art biomedical named entity tagger. Results: Our results show: that performance across different evaluation corpora is extremely variable; that the use of tagged (as opposed to gold standard) gene and protein names has a significant impact on performance, with a drop in F-score of over 20 percentage points being commonplace; and that a simple keyword-based benchmark algorithm when coupled with a named entity tagger outperforms two of the tools most widely used to extract gene/protein interactions. Conclusion: In terms of availability, ease of use and performance, the potential non-specialist user community interested in automatically extracting gene and/or protein interactions from free text is poorly served by current tools and systems. The public release of extraction tools that are easy to install and use, and that achieve state-of-art levels of performance should be treated as a high priority by the biomedical text mining community

Determination of Pericardial Adipose Tissue Increases the Prognostic Accuracy of Coronary Artery Calcification for Future Cardiovascular Events

Objectives: Pericardial adipose tissue (PAT) is associated with coronary artery plaque accumulation and the incidence of coronary heart disease. We evaluated the possible incremental prognostic value of PAT for future cardiovascular events. Methods: 145 patients (94 males, age 60 10 years) with stable coronary artery disease underwent coronary artery calcification (CAC) scanning in a multislice CT scanner, and the volume of pericardial fat was measured. Mean observation time was 5.4 years. Results: 34 patients experienced a severe cardiac event. They had a significantly higher CAC score (1,708 +/- 2,269 vs. 538 +/- 1,150, p 400, 3.5 (1.9-5.4; p = 0.007) for scores > 800 and 5.9 (3.7-7.8; p = 0.005) for scores > 1,600. When additionally a PAT volume > 200 cm(3) was determined, there was a significant increase in the event rate and relative risk. We calculated a relative risk of 2.9 (1.9-4.2; p = 0.01) for scores > 400, 4.0 (2.1-5.0; p = 0.006) for scores > 800 and 7.1 (4.1-10.2; p = 0.005) for scores > 1,600. Conclusions:The additional determination of PAT increases the predictive power of CAC for future cardiovascular events. PAT might therefore be used as a further parameter for risk stratification. Copyright (C) 2012 S. Karger AG, Base

Long-Term Effects of the Cleaner Fish Labroides dimidiatus on Coral Reef Fish Communities

Cleaning behaviour is deemed a mutualism, however the benefit of cleaning interactions to client individuals is unknown. Furthermore, mechanisms that may shift fish community structure in the presence of cleaning organisms are unclear. Here we show that on patch reefs (61–285 m2) which had all cleaner wrasse Labroides dimidiatus (Labridae) experimentally removed (1–5 adults reef−1) and which were then maintained cleaner-fish free over 8.5 years, individuals of two site-attached (resident) client damselfishes (Pomacentridae) were smaller compared to those on control reefs. Furthermore, resident fishes were 37% less abundant and 23% less species rich per reef, compared to control reefs. Such changes in site-attached fish may reflect lower fish growth rates and/or survivorship. Additionally, juveniles of visitors (fish likely to move between reefs) were 65% less abundant on removal reefs suggesting cleaners may also affect recruitment. This may, in part, explain the 23% lower abundance and 33% lower species richness of visitor fishes, and 66% lower abundance of visitor herbivores (Acanthuridae) on removal reefs that we also observed. This is the first study to demonstrate a benefit of cleaning behaviour to client individuals, in the form of increased size, and to elucidate potential mechanisms leading to community-wide effects on the fish population. Many of the fish groups affected may also indirectly affect other reef organisms, thus further impacting the reef community. The large-scale effect of the presence of the relatively small and uncommon fish, Labroides dimidiadus, on other fishes is unparalleled on coral reefs

Stability of static walls for a three-dimensional model of ferromagnetic material.

ACLInternational audienceIn this paper we consider a three dimensional model of ferromagnetic material. We deal with the static domain wall configuration calculated by Walker. We prove the stability of this configuration for the Landau-Lifschitz equation with a simplified expression of the demagnetizing field. Résumé. Dans cet article, on considère un modèle tridimensionnel de matériau ferromagnétique. OnétudieOnétudie les profils de murs statiques calculés initialement par Walker. On démontre la sta-bilité de ces profils pour l'´ equation de Landau-Lifschitz avec un modèle simplifié pour le champ démagnétisant

In-medium hadronic spectral functions through the soft-wall holographic model of QCD

We study the scalar glueball and vector meson spectral functions in a hot and dense medium by means of the soft-wall holographic model of QCD. Finite temperature and density effects are implemented through the AdS/RN metric. We analyse the behaviour of the hadron masses and widths in the $(T,\mu)$ plane, and compare our results with the experimental ones and with other theoretical determinations.Comment: 16 pages, 6 figures. matching the published versio

Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors.

BackgroundIn 31 solid tumor patients treated with the demethylating agent decitabine, we performed tumor biopsies before and after the first cycle of decitabine and used immunohistochemistry (IHC) to assess whether decitabine increased expression of various membrane transporters. Resistance to chemotherapy may arise due to promoter methylation/downregulation of expression of transporters required for drug uptake, and decitabine can reverse resistance in vitro. The endocytosis regulator RhoA, the folate carriers FOLR1 and RFC1, and the glucose transporter GLUT4 were assessed.ResultsPre-decitabine RhoA was higher in patients who had received their last therapy >3 months previously than in patients with more recent prior therapy (P = 0.02), and varied inversely with global DNA methylation as assessed by LINE1 methylation (r = -0.58, P = 0.006). Tumor RhoA scores increased with decitabine (P = 0.03), and RFC1 also increased in patients with pre-decitabine scores ≤150 (P = 0.004). Change in LINE1 methylation with decitabine did not correlate significantly with change in IHC scores for any transporter assessed. We also assessed methylation of the RFC1 gene (alias SLC19A1). SLC19A1 methylation correlated with tumor LINE1 methylation (r = 0.45, P = 0.02). There was a small (statistically insignificant) decrease in SLC19A1 methylation with decitabine, and there was a trend towards change in SLC19A1 methylation with decitabine correlating with change in LINE1 methylation (r = 0.47, P <0.15). While SLC19A1 methylation did not correlate with RFC1 scores, there was a trend towards an inverse correlation between change in SLC19A1 methylation and change in RFC1 expression (r = -0.45, P = 0.19).ConclusionsIn conclusion, after decitabine administration, there was increased expression of some (but not other) transporters that may play a role in chemotherapy uptake. Larger patient numbers will be needed to define the extent to which this increased expression is associated with changes in DNA methylation