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

A highly conserved gene island of three genes on chromosome 3B of hexaploid wheat: diverse gene function and genomic structure maintained in a tightly linked block

The complexity of the wheat genome has resulted from waves of retrotransposable element insertions. Gene deletions and disruptions generated by the fast replacement of repetitive elements in wheat have resulted in disruption of colinearity at a micro (sub-megabase) level among the cereals. In view of genomic changes that are possible within a given time span, conservation of genes between species tends to imply an important functional or regional constraint that does not permit a change in genomic structure. The ctg1034 contig completed in this paper was initially studied because it was assigned to the Sr2 resistance locus region, but detailed mapping studies subsequently assigned it to the long arm of 3B and revealed its unusual features

Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes

Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain. We used nonparametric gene set analysis to test for age-related enrichment of genes associated with specific cell-types; we also restricted our analyses to specific gene ontology groups. Our analyses focused on a primary pair of single-cell expression data from the mouse visual cortex and age-related human post-mortem gene expression information from the orbitofrontal cortex. Additional pairings that used data from the hippocampus, prefrontal cortex, somatosensory cortex and blood were used to validate and test specificity of our findings. We found robust age-related up-regulation of genes that are highly expressed in oligodendrocytes and astrocytes, while genes highly expressed in layer 2/3 glutamatergic neurons were down-regulated across age. Genes not specific to any neural cell type were also down-regulated, possibly due to the bulk tissue source of the age-related genes. A gene ontology-driven dissection of the cell-type enriched genes highlighted the strong down-regulation of genes involved in synaptic transmission and cell-cell signaling in the Somatostatin (Sst) neuron subtype that expresses the cyclin dependent kinase 6 (Cdk6) and in the vasoactive intestinal peptide (Vip) neuron subtype expressing myosin binding protein C, slow type (Mybpc1). These findings provide new insights into cell specific susceptibility to normal aging, and suggest age-related synaptic changes in specific inhibitory neuron subtypes

Infrared and microwaves at 5.8 GHz in a catalytic reactor

An improved micro-reactor cell for IR spectroscopic studies of heterogeneous catalysis was built around a 5.8 GHz microwave cavity. The reactor can operate at 20 bars and with conventional heating up to 720 K, with reactant gas flows velocities (GHSV) from 25 000 to 50 000 h−1. The temperature of the sample under microwave irradiation was measured by time resolved IR emission spectroscopy. The first experiment performed was the IR monitoring of the desorption of carbonates induced by irradiating an alumina sample by microwaves at 5.8 GHz

High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens

After vaccination of melanoma patients with MAGE antigens, we observed that even in the few patients showing tumor regression, the frequency of anti-vaccine T cells in the blood was often either undetectable or <10−5 of CD8 T cells. This frequency being arguably too low for these cells to be sole effectors of rejection, we reexamined the contribution of T cells recognizing other tumor antigens. The presence of such antitumor T cells in melanoma patients has been widely reported. To begin assessing their contribution to vaccine-induced rejection, we evaluated their blood frequency in five vaccinated patients. The antitumor cytotoxic T lymphocyte (CTL) precursors ranged from 10−4 to 3 × 10−3, which is 10–10,000 times higher than the anti-vaccine CTL in the same patient. High frequencies were also observed before vaccination. In a patient showing nearly complete regression after vaccination with a MAGE-3 antigen, we observed a remarkably focused antitumoral response. A majority of CTL precursors (CTLp's) recognized antigens encoded by MAGE-C2, another cancer-germline gene. Others recognized gp100 antigens. CTLp's recognizing MAGE-C2 and gp100 antigens were already present before vaccination, but new clonotypes appeared afterwards. These results suggest that a spontaneous antitumor T cell response, which has become ineffective, can be reawakened by vaccination and contribute to tumor rejection. This notion is reinforced by the frequencies of anti-vaccine and antitumor CTLs observed inside metastases, as presented by Lurquin et al. (Lurquin, C., B. Lethé, V. Corbière, I. Théate, N. van Baren, P.G. Coulie, and T. Boon. 2004. J. Exp. Med. 201:249–257)

Variations in water use by a mature mangrove of Avicennia germinans, French Guiana

In the tropical intertidal zones, little is known on water uptake by mangroves. Transpiration rates are generally measured at leaf level, but few studies exist on water use at tree or stand levels. The objective of this study was to measure sap flow in trees of different sizes to appreciate the range of variation in water use that may exist in a site dominated by 80% mature Avicennia germinans. The results showed that from the dry to the wet season the mean water use increased from 3.2 to 5.3 dm3 d−1 in small trees (DBH ∼ 13 cm), from 11.5 to 30.8 dm3 d−1 in medium trees (∼24 cm) and from 40.8 to 64.1 dm3 d−1 in large ones (∼45 cm). Sapwood remained active up to a depth of 8 cm with radial variations within the stem. Weak correlations were obtained with VPD and net radiation. This study confirmed that transpiration was larger under low levels of salinity. Water use at stand level (∼1900 living stems ha−1) was estimated to be in the range of 5.8 to 11.8 m3 ha−1 d−1 according to the season

Emotional reactions to cybersecurity breach situations: A scenario-based survey study

Background: With the ever-expanding interconnectedness through the internet, and especially with the recent development of the Internet of Things (IoT), people are increasingly at risk for cybersecurity breaches that can have far-reaching consequences for one’s personal and professional lives, with psychological and mental health ramifications. Objective: We aim to identify the dimensional structure of emotion processes triggered by one of the most emblematic scenarios of cybersecurity breach, the hacking of one’s smart security camera, and to explore which personality characteristics systematically relate to these emotion dimensions. Methods: A total of 902 participants from the United Kingdom and the Netherlands reported their emotion processes triggered by a cybersecurity breach scenario. Moreover, they reported on their Big Five personality traits, as well as on key indicators for resilient, over-controlling (internalizing problems), and under-controlling (aggression) personality types. Results: Principal component analyses revealed a clear three-dimensional structure of emotion processes: emotional intensity, proactive vs fight/flight reactions, and affective vs cognitive/motivational reactions. Regression analyses revealed that more internalizing problems (β = .33, p < .001), resilience (β = .22, P < .001), and agreeableness (β = .12, P < .001, and less emotional stability (β = -.25, P < .001) have significant predictive value for higher emotional intensity. More internalizing problems (β = .26, P < .001), aggression (β = .25, P < .001), extraversion (β = .07, p = .01), and less resilience (β = -.19, P < .001), agreeableness (β = -.34, P < .001), consciousness (β = -.19, P < .001), and openness (β = -.22, P < .001) have significant predictive value for comparatively more fight/flight than proactive reactions. Less internalizing problems (β = -.32, P < .001), and more emotional stability (β = .14, P < .001), and aggression (β = .13, P < .001) have significant predictive value for a comparatively higher salience for cognitive/motivational than affective reactions. Conclusion: To adequately describe the emotion processes triggered by a cybersecurity breach, two more dimensions are needed over and above the general negative affectivity dimension. This multidimensional structure is further supported by the differential relationships of the emotion dimensions with personality characteristics. The discovered emotion structure could be used for consistent predictions about who is at risk to develop long-term mental well-being issues due to a cybersecurity breach experience