Improved predictability of the troposphere using stratospheric final warmings

The final warming of the stratospheric polar vortex at the end of northern hemisphere winter is examined in ECMWF ERA-Interim reanalysis data and an ensemble of chemistry climate models, using 20 years of data from each. In some years the final warming is found to occur first in the mid-stratosphere, and in others to occur first in the upper stratosphere. The strength of the winter stratospheric polar vortex, refraction of planetary waves, and the altitudes at which the planetary waves break in the northern extratropics lead to this difference in the vertical profile of the final warming. Years in which the final warming occurs first in the mid-stratosphere show, on average, a more negative NAO pattern in April mean sea level pressure than years in which the warming occurs first in the upper stratosphere. Thus, in the northern hemisphere, additional predictive skill of tropospheric climate in April can be gained from a knowledge of the vertical profile of the stratospheric final warming.

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants.

The effect of climate change on the variability of the Northern Hemisphere stratospheric polar vortex

With extreme variability of the Arctic polar vortex being a key link for stratosphere–troposphere influences, its evolution into the twenty-first century is important for projections of changing surface climate in response to greenhouse gases. Variability of the stratospheric vortex is examined using a state-of-the-art climate model and a suite of specifically developed vortex diagnostics. The model has a fully coupled ocean and a fully resolved stratosphere. Analysis of the standard stratospheric zonal mean wind diagnostic shows no significant increase over the twenty-first century in the number of major sudden stratospheric warmings (SSWs) from its historical value of 0.7 events per decade, although the monthly distribution of SSWs does vary, with events becoming more evenly dispersed throughout the winter. However, further analyses using geometric-based vortex diagnostics show that the vortex mean state becomes weaker, and the vortex centroid is climatologically more equatorward by up to 2.5°, especially during early winter. The results using these diagnostics not only characterize the vortex structure and evolution but also emphasize the need for vortex-centric diagnostics over zonally averaged measures. Finally, vortex variability is subdivided into wave-1 (displaced) and -2 (split) components, and it is implied that vortex displacement events increase in frequency under climate change, whereas little change is observed in splitting events.

Climate change projections and stratosphere–troposphere interaction

Climate change is expected to increase winter rainfall and flooding in many extratropical regions as evaporation and precipitation rates increase, storms become more intense and storm tracks move polewards. Here, we show how changes in stratospheric circulation could play a significant role in future climate change in the extratropics through an additional shift in the tropospheric circulation. This shift in the circulation alters climate change in regional winter rainfall by an amount large enough to significantly alter regional climate change projections. The changes are consistent with changes in stratospheric winds inducing a change in the baroclinic eddy growth rate across the depth of the troposphere. A change in mean wind structure and an equatorward shift of the tropospheric storm tracks relative to models with poor stratospheric resolution allows coupling with surface climate. Using the Atlantic storm track as an example, we show how this can double the predicted increase in extreme winter rainfall over Western and Central Europe compared to other current climate projections

Stratosphere‐troposphere coupling and annular mode variability in chemistry‐climate models

The internal variability and coupling between the stratosphere and troposphere in CCMVal‐2 chemistry‐climate models are evaluated through analysis of the annular mode patterns of variability. Computation of the annular modes in long data sets with secular trends requires refinement of the standard definition of the annular mode, and a more robust procedure that allows for slowly varying trends is established and verified. The spatial and temporal structure of the models’ annular modes is then compared with that of reanalyses. As a whole, the models capture the key features of observed intraseasonal variability, including the sharp vertical gradients in structure between stratosphere and troposphere, the asymmetries in the seasonal cycle between the Northern and Southern hemispheres, and the coupling between the polar stratospheric vortices and tropospheric midlatitude jets. It is also found that the annular mode variability changes little in time throughout simulations of the 21st century. There are, however, both common biases and significant differences in performance in the models. In the troposphere, the annular mode in models is generally too persistent, particularly in the Southern Hemisphere summer, a bias similar to that found in CMIP3 coupled climate models. In the stratosphere, the periods of peak variance and coupling with the troposphere are delayed by about a month in both hemispheres. The relationship between increased variability of the stratosphere and increased persistence in the troposphere suggests that some tropospheric biases may be related to stratospheric biases and that a well‐simulated stratosphere can improve simulation of tropospheric intraseasonal variability.

Meta-analysis of the INSIG2 association with obesity including 74,345 individuals: does heterogeneity of estimates relate to study design?

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI> or =30 kg/m(2)) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status ('healthy population', HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I(2) measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I(2) measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI> or =32.5, 35.0, 37.5, 40.0 kg/m(2) versus BMI<25 kg/m(2)) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far.

Are power calculations useful? A multicentre neuroimaging study

There are now many reports of imaging experiments with small cohorts of typical participants that precede large-scale, often multicentre studies of psychiatric and neurological disorders. Data from these calibration experiments are sufficient to make estimates of statistical power and predictions of sample size and minimum observable effect sizes. In this technical note, we suggest how previously reported voxel-based power calculations can support decision making in the design, execution and analysis of cross-sectional multicentre imaging studies. The choice of MRI acquisition sequence, distribution of recruitment across acquisition centres, and changes to the registration method applied during data analysis are considered as examples. The consequences of modification are explored in quantitative terms by assessing the impact on sample size for a fixed effect size and detectable effect size for a fixed sample size. The calibration experiment dataset used for illustration was a precursor to the now complete Medical Research Council Autism Imaging Multicentre Study (MRC-AIMS). Validation of the voxel-based power calculations is made by comparing the predicted values from the calibration experiment with those observed in MRC-AIMS. The effect of non-linear mappings during image registration to a standard stereotactic space on the prediction is explored with reference to the amount of local deformation. In summary, power calculations offer a validated, quantitative means of making informed choices on important factors that influence the outcome of studies that consume significant resources.

Adjustments in the forcing-feedback framework for understanding climate change

The traditional forcing-feedback framework has provided an indispensable basis for discussing global climate changes. However, as analysis of model behavior has become more detailed, shortcomings and ambiguities in the framework have become more evident and physical effects unaccounted for by the traditional framework have become interesting. In particular, the new concept of adjustments, which are responses to forcings that are not mediated by the global mean temperature, has emerged. This concept, related to the older ones of climate efficacy and stratospheric adjustment, is a more physical way of capturing unique responses to specific forcings. We present a pedagogical review of the adjustment concept, why it is important, and how it can be used. The concept is particularly useful for aerosols, where it helps to organize what has become a complex array of forcing mechanisms. It also helps clarify issues around cloud and hydrological response, transient vs. equilibrium climate change, and geoengineering.

Clouds, circulation and climate sensitivity

Fundamental puzzles of climate science remain unsolved because of our limited understanding of how clouds, circulation and climate interact. One example is our inability to provide robust assessments of future global and regional climate changes. However, ongoing advances in our capacity to observe, simulate and conceptualize the climate system now make it possible to fill gaps in our knowledge. We argue that progress can be accelerated by focusing research on a handful of important scientific questions that have become tractable as a result of recent advances. We propose four such questions below; they involve understanding the role of cloud feedbacks and convective organization in climate, and the factors that control the position, the strength and the variability of the tropical rain belts and the extratropical storm tracks.

Atypical processing of voice sounds in infants at risk for Autism Spectrum Disorder

Adults diagnosed with autism spectrum disorder (ASD) show a reduced sensitivity (degree of selective response) to social stimuli such as human voices. In order to determine whether this reduced sensitivity is a consequence of years of poor social interaction and communication or is present prior to significant experience, we used functional MRI to examine cortical sensitivity to auditory stimuli in infants at high familial risk for later emerging ASD (HR group, N = 15), and compared this to infants with no family history of ASD (LR group, N = 18). The infants (aged between 4 and 7 months) were presented with voice and environmental sounds while asleep in the scanner and their behaviour was also examined in the context of observed parent-infant interaction. Whereas LR infants showed early specialisation for human voice processing in right temporal and medial frontal regions, the HR infants did not. Similarly, LR infants showed stronger sensitivity than HR infants to sad vocalisations in the right fusiform gyrus and left hippocampus. Also, in the HR group only, there was an association between each infant's degree of engagement during social interaction and the degree of voice sensitivity in key cortical regions. These results suggest that at least some infants at high-risk for ASD have atypical neural responses to human voice with and without emotional valence. Further exploration of the relationship between behaviour during social interaction and voice processing may help better understand the mechanisms that lead to different outcomes in at risk populations.

The impact of two coupled cirrus microphysics-radiation parameterizations on the temperature and specific humidity biases in the tropical tropopause layer in a climate model

The impact of two different coupled cirrus microphysics-radiation parameterizations on the zonally averaged temperature and humidity biases in the tropical tropopause layer (TTL) of a Met Office climate model configuration is assessed. One parameterization is based on a linear coupling between a model prognostic variable, the ice mass mixing ratio, qi, and the integral optical properties. The second is based on the integral optical properties being parameterized as functions of qi and temperature, Tc, where the mass coefficients (i.e. scattering and extinction) are parameterized as nonlinear functions of the ratio between qi and Tc. The cirrus microphysics parameterization is based on a moment estimation parameterization of the particle size distribution (PSD), which relates the mass moment (i.e. second moment if mass is proportional to size raised to the power of 2 ) of the PSD to all other PSD moments through the magnitude of the second moment and Tc. This same microphysics PSD parameterization is applied to calculate the integral optical properties used in both radiation parameterizations and, thus, ensures PSD and mass consistency between the cirrus microphysics and radiation schemes. In this paper, the temperature-non-dependent and temperature-dependent parameterizations are shown to increase and decrease the zonally averaged temperature biases in the TTL by about 1 K, respectively. The temperature-dependent radiation parameterization is further demonstrated to have a positive impact on the specific humidity biases in the TTL, as well as decreasing the shortwave and longwave biases in the cloudy radiative effect. The temperature-dependent radiation parameterization is shown to be more consistent with TTL and global radiation observations.

Storytelling in song: television music, narrative and allusion in 'The O.C.'

Television’s long-form storytelling has the potential to allow the rippling of music across episodes and seasons in interesting ways. In the integration of narrative, music and meaning found in The O.C. (Fox, FOX 2003-7), popular song’s allusive and referential qualities are drawn upon to particularly televisual ends. At times embracing its ‘disruptive’ presence, at others suturing popular music into narrative, at times doing both at once. With television studies largely lacking theories of music, this chapter draws on film music theory and close textual analysis to analyse some of the programme's music moments in detail. In particular it considers the series-spanning use of Jeff Buckley’s cover of ‘Hallelujah’ (and its subsequent oppressive presence across multiple televisual texts), the end of episode musical montage and the use of recurring song fragments as theme within single episodes. In doing so it highlights music's role in the fragmentation and flow of the television aesthetic and popular song’s structural presence in television narrative. Illustrating the multiplicity of popular song’s use in television, these moments demonstrate song’s ability to provide narrative commentary, yet also make particular use of what Ian Garwood describes as the ability of ‘a non-diegetic song to exceed the emotional range displayed by diegetic characters’ (2003:115), to ‘speak’ for characters or to their feelings, contributing to both teen TV’s melodramatic affect and narrative expression.

Syk and Src family kinases regulate C-type lectin receptor 2 (CLEC-2)-mediated clustering of podoplanin and platelet adhesion to lymphatic endothelial cells

The interaction of C-type lectin receptor 2 (CLEC-2) on platelets with Podoplanin on lymphatic endothelial cells initiates platelet signaling events that are necessary for prevention of blood-lymph mixing during development. In the present study, we show that CLEC-2 signaling via Src family and Syk tyrosine kinases promotes platelet adhesion to primary mouse lymphatic endothelial cells at low shear. Using supported lipid bilayers containing mobile Podoplanin, we further show that activation of Src and Syk in platelets promotes clustering of CLEC-2 and Podoplanin. Clusters of CLEC-2-bound Podoplanin migrate rapidly to the center of the platelet to form a single structure. Fluorescence lifetime imaging demonstrates that molecules within these clusters are within 10 nm of one another and that the clusters are disrupted by inhibition of Src and Syk family kinases. CLEC-2 clusters are also seen in platelets adhered to immobilized Podoplanin using direct stochastic optical reconstruction microscopy. These findings provide mechanistic insight by which CLEC-2 signaling promotes adhesion to Podoplanin and regulation of Podoplanin signaling, thereby contributing to lymphatic vasculature development.