GEIRA: gene-environment and gene–gene interaction research application

The GEIRA (Gene-Environment and Gene–Gene Interaction Research Application) algorithm and subsequent program is dedicated to genome-wide gene-environment and gene–gene interaction analysis. It implements concepts of both additive and multiplicative interaction as well as calculations based on dominant, recessive and co-dominant genetic models, respectively. Estimates of interactions are incorporated in a single table to make the output easily read. The algorithm is coded in both SAS and R. GEIRA is freely available to non-commercial users at http://www.epinet.se. Additional information, including user’s manual and example datasets is available online at http://www.epinet.se

Controllable Synthesis of Magnesium Oxysulfate Nanowires with Different Morphologies

One-dimensional magnesium oxysulfate 5Mg(OH)2 · MgSO4 · 3H2O (abbreviated as 513MOS) with high aspect ratio has attracted much attention because of its distinctive properties from those of the conventional bulk materials. 513MOS nanowires with different morphologies were formed by varying the mixing ways of MgSO4 · 7H2O and NH4OH solutions at room temperature followed by hydrothermal treatment of the slurries at 150 °C for 12 h with or without EDTA. 513MOS nanowires with a length of 20–60 μm and a diameter of 60–300 nm were prepared in the case of double injection (adding MgSO4 · 7H2O and NH4OH solutions simultaneously into water), compared with the 513MOS with a length of 20–30 μm and a diameter of 0.3–1.7 μm in the case of the single injection (adding MgSO4 · 7H2O solution into NH4OH solution). The presence of minor amount of EDTA in the single injection method led to the formation of 513MOS nanowires with a length of 100–200 μm, a diameter of 80–200 nm, and an aspect ratio of up to 1000. The analysis of the experimental results indicated that the hydrothermal solutions with a lower supersaturation were favorable for the preferential growth of 513MOS nanowires along b axis

Kank Is an EB1 Interacting Protein that Localises to Muscle-Tendon Attachment Sites in Drosophila

Little is known about how microtubules are regulated in different cell types during development. EB1 plays a central role in the regulation of microtubule plus ends. It directly binds to microtubule plus ends and recruits proteins which regulate microtubule dynamics and behaviour. We report the identification of Kank, the sole Drosophila orthologue of human Kank proteins, as an EB1 interactor that predominantly localises to embryonic attachment sites between muscle and tendon cells. Human Kank1 was identified as a tumour suppressor and has documented roles in actin regulation and cell polarity in cultured mammalian cells. We found that Drosophila Kank binds EB1 directly and this interaction is essential for Kank localisation to microtubule plus ends in cultured cells. Kank protein is expressed throughout fly development and increases during embryogenesis. In late embryos, it accumulates to sites of attachment between muscle and epidermal cells. A kank deletion mutant was generated. We found that the mutant is viable and fertile without noticeable defects. Further analysis showed that Kank is dispensable for muscle function in larvae. This is in sharp contrast to C. elegans in which the Kank orthologue VAB-19 is required for development by stabilising attachment structures between muscle and epidermal cells

The northern hemisphere circumglobal teleconnection in a seasonal forecast model and its relationship to European summer forecast skill

Forecasting seasonal variations in European summer weather represents a considerable challenge. Here, we assess the performance of a seasonal forecasting model at representing a major mode of northern hemisphere summer climate variability, the circumglobal teleconnection (CGT), and the implications of errors in its representation on seasonal forecasts for the European summer (June, July, August). Using seasonal hindcasts initialised at the start of May, we find that the model skill for forecasting the interannual variability of 500 hPa geopotential height is poor, particularly over Europe and several other “centres of action” of the CGT. The model also has a weaker CGT pattern than is observed, particularly in August, when the observed CGT wavetrain is strongest. We investigate several potential causes of this poor skill. First, model variance in geopotential height in west-central Asia (an important region for the maintenance of the CGT) is lower than observed in July and August, associated with a poor representation of the link between this region and Indian monsoon precipitation. Second, analysis of the Rossby wave source shows that the source associated with monsoon heating is both too strong and displaced to the northeast in the model. This is related to errors in monsoon precipitation over the Bay of Bengal and Arabian Sea, where the model has more precipitation than is observed. Third, the model jet is systematically shifted northwards by several degrees latitude over large parts of the northern hemisphere, which may affect the propagation characteristics of Rossby waves in the model

Robust observational constraint of uncertain aerosol processes and emissions in a climate model and the effect on aerosol radiative forcing

The effect of observational constraint on the ranges of uncertain physical and chemical process parameters was explored in a global aerosol–climate model. The study uses 1 million variants of the Hadley Centre General Environment Model version 3 (HadGEM3) that sample 26 sources of uncertainty, together with over 9000 monthly aggregated grid-box measurements of aerosol optical depth, PM2.5, particle number concentrations, sulfate and organic mass concentrations. Despite many compensating effects in the model, the procedure constrains the probability distributions of parameters related to secondary organic aerosol, anthropogenic SO2 emissions, residential emissions, sea spray emissions, dry deposition rates of SO2 and aerosols, new particle formation, cloud droplet pH and the diameter of primary combustion particles. Observational constraint rules out nearly 98 % of the model variants. On constraint, the ±1σ (standard deviation) range of global annual mean direct radiative forcing (RFari) is reduced by 33 % to −0.14 to −0.26 W m−2, and the 95 % credible interval (CI) is reduced by 34 % to −0.1 to −0.32 W m−2. For the global annual mean aerosol–cloud radiative forcing, RFaci, the ±1σ range is reduced by 7 % to −1.66 to −2.48 W m−2, and the 95 % CI by 6 % to −1.28 to −2.88 W m−2. The tightness of the constraint is limited by parameter cancellation effects (model equifinality) as well as the large and poorly defined “representativeness error” associated with comparing point measurements with a global model. The constraint could also be narrowed if model structural errors that prevent simultaneous agreement with different measurement types in multiple locations and seasons could be improved. For example, constraints using either sulfate or PM2.5 measurements individually result in RFari±1σ ranges that only just overlap, which shows that emergent constraints based on one measurement type may be overconfident

Development of a mathematical model for predicting electrically elicited quadriceps femoris muscle forces during isovelocity knee joint motion

<p>Abstract</p> <p>Background</p> <p>Direct electrical activation of skeletal muscles of patients with upper motor neuron lesions can restore functional movements, such as standing or walking. Because responses to electrical stimulation are highly nonlinear and time varying, accurate control of muscles to produce functional movements is very difficult. Accurate and predictive mathematical models can facilitate the design of stimulation patterns and control strategies that will produce the desired force and motion. In the present study, we build upon our previous isometric model to capture the effects of constant angular velocity on the forces produced during electrically elicited concentric contractions of healthy human quadriceps femoris muscle. Modelling the isovelocity condition is important because it will enable us to understand how our model behaves under the relatively simple condition of constant velocity and will enable us to better understand the interactions of muscle length, limb velocity, and stimulation pattern on the force produced by the muscle.</p> <p>Methods</p> <p>An additional term was introduced into our previous isometric model to predict the force responses during constant velocity limb motion. Ten healthy subjects were recruited for the study. Using a KinCom dynamometer, isometric and isovelocity force data were collected from the human quadriceps femoris muscle in response to a wide range of stimulation frequencies and patterns. % error, linear regression trend lines, and paired t-tests were used to test how well the model predicted the experimental forces. In addition, sensitivity analysis was performed using Fourier Amplitude Sensitivity Test to obtain a measure of the sensitivity of our model's output to changes in model parameters.</p> <p>Results</p> <p>Percentage RMS errors between modelled and experimental forces determined for each subject at each stimulation pattern and velocity showed that the errors were in general less than 20%. The coefficients of determination between the measured and predicted forces show that the model accounted for ~86% and ~85% of the variances in the measured force-time integrals and peak forces, respectively.</p> <p>Conclusion</p> <p>The range of predictive abilities of the isovelocity model in response to changes in muscle length, velocity, and stimulation frequency for each individual make it ideal for dynamic applications like FES cycling.</p

Techniques for accurate protein identification in shotgun proteomic studies of human, mouse, bovine, and chicken lenses

Analysis of shotgun proteomics datasets requires techniques to distinguish correct peptide identifications from incorrect identifications, such as linear discriminant functions and target/decoy protein databases. We report an efficient, flexible proteomic analysis workflow pipeline that implements these techniques to control both peptide and protein false discovery rates. We demonstrate its performance by analyzing two-dimensional liquid chromatography separations of lens proteins from human, mouse, bovine, and chicken lenses. We compared the use of International Protein Index databases to UniProt databases and no-enzyme SEQUEST searches to tryptic searches. Sequences present in the International Protein Index databases allowed detection of several novel crystallins. An alternate start codon isoform of βA4 was found in human lens. The minor crystallin γN was detected for the first time in bovine and chicken lenses. Chicken γS was identified and is the first member of the γ-crystallin family observed in avian lenses

Small RNA analysis in Sindbis virus infected human HEK293 cells

In contrast to the defence mechanism of RNA interference (RNAi) in plants and invertebrates, its role in the innate response to virus infection of mammals is a matter of debate. Since RNAi has a well-established role in controlling infection of the alphavirus Sindbis virus (SINV) in insects, we have used this virus to investigate the role of RNAi in SINV infection of human cells

Influence of the physical dimension of leaf size measures on the goodness of fit for Taylor's power law using 101 bamboo taxa

The mean and variance of ecological measures usually follow a power-law relationship, referred to as Taylor's power law (TPL). Leaves are important organs for photosynthesis, and leaf size is closely related to photosynthetic potential. Leaf size has different physical measures, such as leaf length, area, and fresh or dry weight. However, it has not been reported whether these leaf size measures follow TPL and whether the estimates of the TPL exponent reflect basic topological constraints. Considering that the variation of leaf size can affect the photosynthetic capacity of leaves and plant competitive abilities in communities, we examined the effects of different physical dimensions of leaf size (including leaf length, area, and fresh and dry weight) on the estimate of the scaling exponent and the goodness of fit of TPL for 101 bamboo species, varieties, forms, and cultivars, using 90-100 leaves for each type of plant. All leaf size measures follow TPL. However, the goodness of fit increases with the physical dimension of the leaf size measure (e.g., from 1D leaf length to 3D leaf weight). Interestingly, no significant differences in the estimates of the TPL exponent were detected among any of the physical dimensions (1D to 3D) because the 95% confidence intervals of the differences between any two groups of bootstrap replicates of the exponents of TPL obtained from different leaf size measures did not include 0. In other words, the TPL exponents of leaf size measures from the different physical dimensions could be deemed identical. We found that leaf dry weight provides the best fit of TPL and the most reliable estimate of the exponent among the four leaf size measures used in this study, perhaps because it is the best representative of the energy allocated to individual leaves

Two spatiotemporally distinct value systems shape reward-based learning in the human brain

Avoiding repeated mistakes and learning to reinforce rewarding decisions is critical for human survival and adaptive actions. Yet, the neural underpinnings of the value systems that encode different decision-outcomes remain elusive. Here coupling single-trial electroencephalography with simultaneously acquired functional magnetic resonance imaging, we uncover the spatiotemporal dynamics of two separate but interacting value systems encoding decision-outcomes. Consistent with a role in regulating alertness and switching behaviours, an early system is activated only by negative outcomes and engages arousal-related and motor-preparatory brain structures. Consistent with a role in reward-based learning, a later system differentially suppresses or activates regions of the human reward network in response to negative and positive outcomes, respectively. Following negative outcomes, the early system interacts and downregulates the late system, through a thalamic interaction with the ventral striatum. Critically, the strength of this coupling predicts participants’ switching behaviour and avoidance learning, directly implicating the thalamostriatal pathway in reward-based learning