Automatic prediction of functional site regions in low-resolution protein structures

World-wide structural genomics initiatives are rapidly accumulating structures for which limited functional information is available. Additionally, state-of-the art structural prediction programs are now capable of generating at least low resolution structural models of target proteins. Accurate detection and classification of functional sites within both solved and modelled protein structures therefore represents an important challenge. We present a fully automatic site detection method, FuncSite, that uses neural network classifiers to predict the location and type of functionally important sites in protein structures. The method is designed primarily to require only backbone residue positions without the need for specific side-chain atoms to be present. In order to highlight effective site detection in low resolution structural models FuncSite was used to screen model proteins generated using mGenTHREADER on a set of newly released structures. We found effective metal site detection even for moderate quality protein models illustrating the robustness of the method.

How reward modulates mimicry: EMG evidence of greater automatic facial mimicry of more rewarding faces

Spontaneous mimicry is a marker of empathy. Conditions characterized by reduced spontaneous mimicry (e.g., autism) also display deficits in sensitivity to social rewards. We tested if spontaneous mimicry of socially rewarding stimuli (happy faces) depends on the reward value of stimuli in 32 typical participants. An evaluative conditioning paradigm was used to associate different reward values with neutral target faces. Subsequently, electromyographic activity over the Zygomaticus Major was measured whilst participants watched video clips of the faces making happy expressions. Higher Zygomaticus Major activity was found in response to happy faces conditioned with high reward versus low reward. Moreover, autistic traits in the general population modulated the extent of spontaneous mimicry of happy faces. This suggests a link between reward and spontaneous mimicry and provides a possible underlying mechanism for the reduced response to social rewards seen in autism.

Resistance to the first and second generation anticoagulant rodenticides: a new perspective

Warfarin resistance was first discovered among Norway rat (Rattus norvegicus) populations in Scotland in 1958 and further reports of resistance, both in this species and in others, soon followed from other parts of Europe and the United States. Researchers quickly defined the practical impact of these resistance phenomena and developed robust methods by which to monitor their spread. These tasks were relatively simple because of the high degree of immunity to warfarin conferred by the resistance genes. Later, the second generation anticoagulants were introduced to control rodents resistant to the warfarin-like compounds, but resistance to difenacoum, bromadiolone and brodifacoum is now reported in certain localities in Europe and elsewhere. However, the adoption of test methods designed initially for use with the first generation compounds to identify resistance to compounds of the second generation has led to some practical difficulties in conducting tests and in establishing meaningful resistance baselines. In particular, the results of certain test methodologies are difficult to interpret in terms of the likely impact on practical control treatments of the resistance phenomena they seek to identify. This paper defines rodenticide resistance in the context of both first and second generation anticoagulants. It examines the advantages and disadvantages of existing laboratory and field methods used in the detection of rodent populations resistant to anticoagulants and proposes some improvements in the application of these techniques and in the interpretation of their results.

Automatic keyphrase extraction: a comparison of methods

There are many published methods available for creating keyphrases for documents. Previous work in the field has shown that in a significant proportion of cases author selected keyphrases are not appropriate for the document they accompany. This requires the use of such automated methods to improve the use of keyphrases. Often the keyphrases are not updated when the focus of a paper changes or include keyphrases that are more classificatory than explanatory. The published methods are all evaluated using different corpora, typically one relevant to their field of study. This not only makes it difficult to incorporate the useful elements of algorithms in future work but also makes comparing the results of each method inefficient and ineffective. This paper describes the work undertaken to compare five methods across a common baseline of six corpora. The methods chosen were term frequency, inverse document frequency, the C-Value, the NC-Value, and a synonym based approach. These methods were compared to evaluate performance and quality of results, and to provide a future benchmark. It is shown that, with the comparison metric used for this study Term Frequency and Inverse Document Frequency were the best algorithms, with the synonym based approach following them. Further work in the area is required to determine an appropriate (or more appropriate) comparison metric.

The effects of institutional distance and headquarters’ financial performance on the generation of environmental standards in multinational companies

This article combines institutional and resources’ arguments to show that the institutional distance between the home and the host country, and the headquarters’ financial performance have a relevant impact on the environmental standardization decision in multinational companies. Using a sample of 135 multinational companies in three different industries with headquarters and subsidiaries based in the USA, Canada, Mexico, France, and Spain, we find that a high environmental institutional distance between headquarters’ and subsidiaries’ countries deters the standardization of environmental practices. On the other hand, high-profit headquarters are willing to standardize their environmental practices, rather than taking advantage of countries with lax environmental protection to undertake more pollution-intensive activities. Finally, we show that headquarters’ financial performance also imposes a moderating effect on the relationship between environmental institutional distance between countries and environmental standardization within the multinational company.

Food restriction reverses the hyper-muscular phenotype and force generation capacity deficit of the myostatin null mouse

Food restriction has a great impact on skeletal muscle mass by inducing muscle protein breakdown to provide substrates for energy production through gluconeogenesis. Genetic models of hyper-muscularity interfere with the normal balance between protein synthesis and breakdown which eventually results in extreme muscle growth. Mutations or deletions in the myostatin gene result in extreme muscle mass. Here we evaluated the impact of food restriction for a period of 5 weeks on skeletal muscle size (i.e., fibre cross-sectional area), fibre type composition and contractile properties (i.e., tetanic and specific force) in myostatin null mice. We found that this hyper-muscular model was more susceptible to catabolic processes than wild type mice. The mechanism of skeletal muscle mass loss was examined and our data shows that the myostatin null mice placed on a low calorie diet maintained the activity of molecules involved in protein synthesis and did not up-regulate the expression of genes pivotal in ubiquitin-mediated protein degradation. However, we did find an increase in the expression of genes associated with autophagy. Surprisingly, the reduction on muscle size was followed by improved tetanic and specific force in the null mice compared to wild type mice. These data provide evidence that food restriction may revert the hyper-muscular phenotype of the myostatin null mouse restoring muscle function.

Root growth models: towards a new generation of continuous approaches

Models of root system growth emerged in the early 1970s, and were based on mathematical representations of root length distribution in soil. The last decade has seen the development of more complex architectural models and the use of computer-intensive approaches to study developmental and environmental processes in greater detail. There is a pressing need for predictive technologies that can integrate root system knowledge, scaling from molecular to ensembles of plants. This paper makes the case for more widespread use of simpler models of root systems based on continuous descriptions of their structure. A new theoretical framework is presented that describes the dynamics of root density distributions as a function of individual root developmental parameters such as rates of lateral root initiation, elongation, mortality, and gravitropsm. The simulations resulting from such equations can be performed most efficiently in discretized domains that deform as a result of growth, and that can be used to model the growth of many interacting root systems. The modelling principles described help to bridge the gap between continuum and architectural approaches, and enhance our understanding of the spatial development of root systems. Our simulations suggest that root systems develop in travelling wave patterns of meristems, revealing order in otherwise spatially complex and heterogeneous systems. Such knowledge should assist physiologists and geneticists to appreciate how meristem dynamics contribute to the pattern of growth and functioning of root systems in the field.

Using meteorological wind data to estimate turbine generation output: a sensitivity analysis

Various studies investigating the future impacts of integrating high levels of renewable energy make use of historical meteorological (met) station data to produce estimates of future generation. Hourly means of 10m horizontal wind are extrapolated to a standard turbine hub height using the wind profile power or log law and used to simulate the hypothetical power output of a turbine at that location; repeating this procedure using many viable locations can produce a picture of future electricity generation. However, the estimate of hub height wind speed is dependent on the choice of the wind shear exponent a or the roughness length z0, and requires a number of simplifying assumptions. This paper investigates the sensitivity of this estimation on generation output using a case study of a met station in West Freugh, Scotland. The results show that the choice of wind shear exponent is a particularly sensitive parameter which can lead to significant variation of estimated hub height wind speed and hence estimated future generation potential of a region.