Signalling Network Construction for Modelling Plant Defence Response

Plant defence signalling response against various pathogens, including viruses, is a complex phenomenon. In resistant interaction a plant cell perceives the pathogen signal, transduces it within the cell and performs a reprogramming of the cell metabolism leading to the pathogen replication arrest. This work focuses on signalling pathways crucial for the plant defence response, i.e., the salicylic acid, jasmonic acid and ethylene signal transduction pathways, in the Arabidopsis thaliana model plant. The initial signalling network topology was constructed manually by defining the representation formalism, encoding the information from public databases and literature, and composing a pathway diagram. The manually constructed network structure consists of 175 components and 387 reactions. In order to complement the network topology with possibly missing relations, a new approach to automated information extraction from biological literature was developed. This approach, named Bio3graph, allows for automated extraction of biological relations from the literature, resulting in a set of (component1, reaction, component2) triplets and composing a graph structure which can be visualised, compared to the manually constructed topology and examined by the experts. Using a plant defence response vocabulary of components and reaction types, Bio3graph was applied to a set of 9,586 relevant full text articles, resulting in 137 newly detected reactions between the components. Finally, the manually constructed topology and the new reactions were merged to form a network structure consisting of 175 components and 524 reactions. The resulting pathway diagram of plant defence signalling represents a valuable source for further computational modelling and interpretation of omics data. The developed Bio3graph approach, implemented as an executable language processing and graph visualisation workflow, is publically available at http://ropot.ijs.si/bio3graph/and can be utilised for modelling other biological systems, given that an adequate vocabulary is provided.     

An ecosystem evaluation framework for global seamount conservation and management

In the last twenty years, several global targets for protection of marine biodiversity have been adopted but have failed. The Convention on Biological Diversity (CBD) aims at preserving 10% of all the marine biomes by 2020. For achieving this goal, ecologically or biologically significant areas (EBSA) have to be identified in all biogeographic regions. However, the methodologies for identifying the best suitable areas are still to be agreed. Here, we propose a framework for applying the CBD criteria to locate potential ecologically or biologically significant seamount areas based on the best information currently available. The framework combines the likelihood of a seamount constituting an EBSA and its level of human impact and can be used at global, regional and local scales. This methodology allows the classification of individual seamounts into four major portfolio conservation categories which can help optimize management efforts toward the protection of the most suitable areas. The framework was tested against 1000 dummy seamounts and satisfactorily assigned seamounts to proper EBSA and threats categories. Additionally, the framework was applied to eight case study seamounts that were included in three out of four portfolio categories: areas highly likely to be identified as EBSA with high degree of threat; areas highly likely to be EBSA with low degree of threat; and areas with a low likelihood of being EBSA with high degree of threat. This framework will allow managers to identify seamount EBSAs and to prioritize their policies in terms of protecting undisturbed areas, disturbed areas for recovery of habitats and species, or both based on their management objectives. It also identifies seamount EBSAs and threats considering different ecological groups in both pelagic and benthic communities. Therefore, this framework may represent an important tool to mitigate seamount biodiversity loss and to achieve the 2020 CBD goals.     

Embedding permanent watermarks in synthetic genes

As synthetic biology advances, labeling of genes or organisms, like other high-value products, will become important not only to pinpoint their identity, origin, or spread, but also for intellectual property, classification, bio-security or legal reasons. Ideally information should be inseparably interlaced into expressed genes. We describe a method for embedding messages within open reading frames of synthetic genes by adapting steganographic algorithms typically used for watermarking digital media files. Text messages are first translated into a binary string, and then represented in the reading frame by synonymous codon choice. To aim for good expression of the labeled gene in its host as well as retain a high degree of codon assignment flexibility for gene optimization, codon usage tables of the target organism are taken into account. Preferably amino acids with 4 or 6 synonymous codons are used to comprise binary digits. Several different messages were embedded into open reading frames of T7 RNA polymerase, GFP, human EMG1 and HIV gag, variously optimized for bacterial, yeast, mammalian or plant expression, without affecting their protein expression or function. We also introduced Vigenère polyalphabetic substitution to cipher text messages, and developed an identifier as a key to deciphering codon usage ranking stored for a specific organism within a sequence of 35 nucleotides.     

Associations between Apolipoprotein E Genotype, Diet, Body Mass Index, and Serum Lipids in Lithuanian Adult Population

Background

Apolipoprotein E (APOE) polymorphism is associated with lipid levels. Some studies have reported that blood lipid response to diet or obesity varies depending on APOE genotypes. The aim of this study was to assess the effect of APOE genotypes, the intake of saturated fatty acids (SFA), and obesity on serum lipid levels in Lithuanian adult population.

Methodology/Principal Findings

A cross-sectional health survey was carried out in five municipalities of Lithuania. The random sample was obtained from lists of 25–64 year-old inhabitants registered at primary health care centres. The data from 996 subjects (416 men and 580 women) were analysed in this study. Two single-nucleotide polymorphisms (rs429358 and rs7412) were assessed using a real-time polymerase chain reaction. 24-hour recall and food frequency questionnaire were used for evaluation of dietary habits. Serum lipids were determined using enzymatic methods.Men and women with the APOE2 genotype had the lowest level of total cholesterol (TC) (p = 0.002 for men, and p = 0.02 for women) and low-density lipoprotein cholesterol (LDL-C) (p<0.001). Multivariate linear regression analysis showed that age, genotype APOE2, SFA intake, and body mass index (BMI) were significant determinants of TC and LDL-C level (with p values ranging from 0.043 to 0.001). Our data did not reveal any statistically significant interactions between APOE genotype and SFA intake or between APOE genotype and BMI regarding TC and LDL-C level (all p>0.05). However, the predictive power of the regression model for LDL-C improved when gene-BMI interaction and gene-BMI interaction plus gene-nutrient interaction were added (p = 0.04 and p = 0.032 for R² change, respectively).

Conclusions/Significance

APOE genotypes, SFA intake, and obesity were found to be associated with blood lipid levels in Lithuanian adult population. Analysis of gene-diet and gene-obesity interactions did not confirm that the effects of diet and obesity on TC and LDL-C level significantly depended on APOE genotype.     

Climate Change: Believing and Seeing Implies Adapting

Knowledge of factors that trigger human response to climate change is crucial for effective climate change policy communication. Climate change has been claimed to have low salience as a risk issue because it cannot be directly experienced. Still, personal factors such as strength of belief in local effects of climate change have been shown to correlate strongly with responses to climate change and there is a growing literature on the hypothesis that personal experience of climate change (and/or its effects) explains responses to climate change. Here we provide, using survey data from 845 private forest owners operating in a wide range of bio-climatic as well as economic-social-political structures in a latitudinal gradient across Europe, the first evidence that the personal strength of belief and perception of local effects of climate change, highly significantly explain human responses to climate change. A logistic regression model was fitted to the two variables, estimating expected probabilities ranging from 0.07 (SD ±0.01) to 0.81 (SD ±0.03) for self-reported adaptive measures taken. Adding socio-demographic variables improved the fit, estimating expected probabilities ranging from 0.022 (SD ±0.008) to 0.91 (SD ±0.02). We conclude that to explain and predict adaptation to climate change, the combination of personal experience and belief must be considered.     

Risk of subsequent coronary heart disease in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden

Background

Certain immune-mediated diseases (IMDs), such as rheumatoid arthritis and systemic lupus erythematosus, have been linked to cardiovascular disorders. We examined whether there is an association between 32 different IMDs and risk of subsequent hospitalization for coronary heart disease (CHD) related to coronary atherosclerosis in a nationwide follow up study in Sweden.

Methods and Findings

All individuals in Sweden hospitalized with a main diagnosis of an IMD (n = 336,479) without previous or coexisting CHD, between January 1, 1964 and December 31 2008, were followed for first hospitalization for CHD. The reference population was the total population of Sweden. Standardized incidence ratios (SIRs) for CHD were calculated. Overall risk of CHD during the first year after hospitalization for an IMD was 2.92 (95% CI 2.84–2.99). Twenty-seven of the 32 IMDs studied were associated with an increased risk of CHD during the first year after hospitalization. The overall risk of CHD decreased over time, from 1.75 after 1–5 years (95% CI 1.73–1.78), to 1.43 after 5–10 years (95% CI 1.41–1.46) and 1.28 after 10+ years (95% CI 1.26–1.30). Females generally had higher SIRs than males. The IMDs for which the SIRs of CDH were highest during the first year after hospitalization included chorea minor 6.98 (95% CI 1.32–20.65), systemic lupus erythematosus 4.94 (95% CI 4.15–5.83), rheumatic fever 4.65 (95% CI 3.53–6.01), Hashimoto''s thyroiditis 4.30 (95% CI 3.87–4.75), polymyositis/dermatomyositis 3.81 (95% CI 2.62–5.35), polyarteritis nodosa 3.81 (95% CI 2.72–5.19), rheumatoid arthritis 3.72 (95% CI 3.56–3.88), systemic sclerosis 3.44 (95% CI 2.86–4.09), primary biliary cirrhosis 3.32 (95% CI 2.34–4.58), and autoimmune hemolytic anemia 3.17 (95% CI 2.16–4.47).

Conclusions

Most IMDs are associated with increased risk of CHD in the first year after hospital admission. Our findings suggest that many hospitalized IMDs are tightly linked to coronary atherosclerosis.     

Sickness Presenteeism Predicts Suboptimal Self-Rated Health and Sickness Absence: A Nationally Representative Study of the Swedish Working Population

Background

Earlier studies have suggested that sickness presenteeism (SP) may be a risk factor for future health problems. The purpose of the present study was to test this in a nationally representative prospective study of Swedish workers.

Methods

Prospective cohort with a representative sample of the Swedish working population surveyed in 2008 and 2010. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using logistic regression.

Results

Those who reported more than 7 days of SP had higher risk of suboptimal SRH compared to those who reported no SP (OR = 5.95; 95% CI 4.98–7.12), also after adjustment for confounders (OR = 1.64; 95% CI 1.30–2.06). Those who reported 1–7 days of SP also had an increased risk before and after adjustments. Inclusion of self-rated physical and psychological work capacity did not attenuate the associations, whereas of emotional exhaustion attenuated the ORs to non-significance for both outcomes, indicating that the health consequences associated with SP are largely related to mental health.

Conclusion

The results strengthen earlier findings suggesting that SP can be a risk factor for future suboptimal general health and sickness absence, particularly through mental health problems. This indicates that asking about SP could yield important information for employers, occupational health practitioners and GPs, possibly leading to more timely intervention that could decrease the risk of future sickness absence and more serious health problems, especially in the mental domain. Further studies of the possible causal pathways between SP and future health development are also warranted, especially since going to work is often seen as desirable also for those with poor health.