Comparative RNAi Screens in C. elegans and C. briggsae Reveal the Impact of Developmental System Drift on Gene Function

Although two related species may have extremely similar phenotypes, the genetic networks underpinning this conserved biology may have diverged substantially since they last shared a common ancestor. This is termed Developmental System Drift (DSD) and reflects the plasticity of genetic networks. One consequence of DSD is that some orthologous genes will have evolved different in vivo functions in two such phenotypically similar, related species and will therefore have different loss of function phenotypes. Here we report an RNAi screen in C. elegans and C. briggsae to identify such cases. We screened 1333 genes in both species and identified 91 orthologues that have different RNAi phenotypes. Intriguingly, we find that recently evolved genes of unknown function have the fastest evolving in vivo functions and, in several cases, we identify the molecular events driving these changes. We thus find that DSD has a major impact on the evolution of gene function and we anticipate that the C. briggsae RNAi library reported here will drive future studies on comparative functional genomics screens in these nematodes.     

The physiological role of reversible methionine oxidation

Sulfur-containing amino acids such as cysteine and methionine are particularly vulnerable to oxidation. Oxidation of cysteine and methionine in their free amino acid form renders them unavailable for metabolic processes while their oxidation in the protein-bound state is a common post-translational modification in all organisms and usually alters the function of the protein. In the majority of cases, oxidation causes inactivation of proteins. Yet, an increasing number of examples have been described where reversible cysteine oxidation is part of a sophisticated mechanism to control protein function based on the redox state of the protein. While for methionine the dogma is still that its oxidation inhibits protein function, reversible methionine oxidation is now being recognized as a powerful means of triggering protein activity. This mode of regulation involves oxidation of methionine to methionine sulfoxide leading to activated protein function, and inactivation is accomplished by reduction of methionine sulfoxide back to methionine catalyzed by methionine sulfoxide reductases. Given the similarity to thiol-based redox-regulation of protein function, methionine oxidation is now established as a novel mode of redox-regulation of protein function. This article is part of a Special Issue entitled: Thiol-Based Redox Processes.     

Genome sequencing of a single cell of the widely distributed marine subsurface Dehalococcoidia,phylum Chloroflexi

Bacteria of the class Dehalococcoidia (DEH), phylum Chloroflexi, are widely distributed in the marine subsurface, yet metabolic properties of the many uncultivated lineages are completely unknown. This study therefore analysed genomic content from a single DEH cell designated ‘DEH-J10'' obtained from the sediments of Aarhus Bay, Denmark. Real-time PCR showed the DEH-J10 phylotype was abundant in upper sediments but was absent below 160 cm below sea floor. A 1.44 Mbp assembly was obtained and was estimated to represent up to 60.8% of the full genome. The predicted genome is much larger than genomes of cultivated DEH and appears to confer metabolic versatility. Numerous genes encoding enzymes of core and auxiliary beta-oxidation pathways were identified, suggesting that this organism is capable of oxidising various fatty acids and/or structurally related substrates. Additional substrate versatility was indicated by genes, which may enable the bacterium to oxidise aromatic compounds. Genes encoding enzymes of the reductive acetyl-CoA pathway were identified, which may also enable the fixation of CO₂ or oxidation of organics completely to CO₂. Genes encoding a putative dimethylsulphoxide reductase were the only evidence for a respiratory terminal reductase. No evidence for reductive dehalogenase genes was found. Genetic evidence also suggests that the organism could synthesise ATP by converting acetyl-CoA to acetate by substrate-level phosphorylation. Other encoded enzymes putatively conferring marine adaptations such as salt tolerance and organo-sulphate sulfohydrolysis were identified. Together, these analyses provide the first insights into the potential metabolic traits that may enable members of the DEH to occupy an ecological niche in marine sediments.     

Big and aerial invaders: dominance of exotic spiders in burned New Zealand tussock grasslands

As post-disturbance community response depends on the characteristics of the ecosystem and the species composition, so does the invasion of exotic species rely on their suitability to the new environment. Here, we test two hypotheses: exotic spider species dominate the community after burning; and two traits are prevalent for their colonisation ability: ballooning and body size, the latter being correlated with their dispersal ability. We established spring burn, summer burn and unburned experimental plots in a New Zealand tussock grassland area and collected annual samples 3 and 4 years before and after the burning, respectively. Exotic spider abundance increased in the two burn treatments, driven by an increase in Linyphiidae. Indicator analysis showed that exotic and native species characterised burned and unburned plots, respectively. Generalised linear mixed-effects models indicated that ballooning had a positive effect on the post-burning establishment (density) of spiders in summer burn plots but not in spring plots. Body size had a positive effect on colonisation and establishment. The ability to balloon may partly explain the dominance of exotic Linyphiidae species. Larger spiders are better at moving into and colonising burned sites probably because of their ability to travel longer distances over land. Native species showed a low resilience to burning, and although confirmation requires longer-term data, our findings suggest that frequent fires could cause long lasting damage to the native spider fauna of tussock grasslands, and we propose limiting the use of fire to essential situations.     

The effects of light and noise from urban development on biodiversity: Implications for protected areas in Australia

Global population growth and associated urban development are having profound effects on biodiversity. Two major outcomes of expanding development that affect wildlife are light and noise pollution. In this paper, we review literature reporting the effects of light and noise on biodiversity, and assess implications for conservation planning in Australia. Our results clearly indicate that light and noise pollution have the potential to affect the physiology, behaviour and reproduction of a range of animal taxa. Types of effects include changes in foraging and reproductive behaviours, reduction in animal fitness, increased risk of predation and reduced reproductive success. These could have flow‐on consequences at the population and ecosystem levels. We found a significant gap in knowledge of the impact of these pollutants on Australian fauna. To reduce the effect of light and noise pollution, there needs to be careful planning of urban areas in relation to protected areas, and for biodiversity more generally. Potential measures include strategically planning the types of development and associated human activities adjacent to protected areas, and the use of shields and barriers, such as covers for lights or the use of dense native vegetation screens, while still allowing movement of animals. Changes in government standards and regulations could also help to reduce the impacts of light and noise pollution.     

An Immunochip-based interrogation of scleroderma susceptibility variants identifies a novel association at DNASE1L3

Introduction

The aim of the study was to interrogate the genetic architecture and autoimmune pleiotropy of scleroderma susceptibility in the Australian population.

Methods

We genotyped individuals from a well-characterized cohort of Australian scleroderma patients with the Immunochip, a custom array enriched for single nucleotide polymorphisms (SNPs) at immune loci. Controls were taken from the 1958 British Birth Cohort. After data cleaning and adjusting for population stratification the final dataset consisted of 486 cases, 4,458 controls and 146,525 SNPs. Association analyses were conducted using logistic regression in PLINK. A replication study was performed using 833 cases and 1,938 controls.

Results

A total of eight loci with suggestive association (P <10^-4.5) were identified, of which five showed significant association in the replication cohort (HLA-DRB1, DNASE1L3, STAT4, TNP03-IRF5 and VCAM1). The most notable findings were at the DNASE1L3 locus, previously associated with systemic lupus erythematosus, and VCAM1, a locus not previously associated with human disease. This study identified a likely functional variant influencing scleroderma susceptibility at the DNASE1L3 locus; a missense polymorphism rs35677470 in DNASE1L3, with an odds ratio of 2.35 (P = 2.3 × 10⁻¹⁰) in anti-centromere antibody (ACA) positive cases.

Conclusions

This pilot study has confirmed previously reported scleroderma associations, revealed further genetic overlap between scleroderma and systemic lupus erythematosus, and identified a putative novel scleroderma susceptibility locus.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0438-8) contains supplementary material, which is available to authorized users.     

Validity and reliability of two brief physical activity questionnaires among Spanish-speaking individuals of Mexican descent

Background

Klebsiella pneumoniae is a leading cause of hospital-acquired urinary tract infections and pneumonia worldwide, and is responsible for many cases of pyogenic liver abscess among diabetic patients in Asia. A defining characteristic of this pathogen is the presence of a thick, exterior capsule that has been reported to play a role in biofilm formation and to protect the organism from threats such antibiotics and host immune challenge.

Findings

We constructed two knockout mutants of K. pneumoniae to investigate how perturbations to capsule biosynthesis alter the cellular phenotype. In the first mutant, we deleted the entire gene cluster responsible for biosynthesis of the extracellular polysaccharide capsule. In the second mutant, we deleted the capsule export subsystem within this cluster. We find that both knockout mutants have lower amounts of capsule but produce greater amounts of biofilm. Moreover, one of the two mutants abolishes fimbriae expression as well.

Conclusions

These results are expected to provide insight into the interaction between capsule biosynthesis, biofilm formation, and fimbriae expression in this organism.     

Sugar Sweetened Beverages and Weight Gain over 4 Years in a Thai National Cohort – A Prospective Analysis

Introduction

Sugar sweetened beverages (SSBs) are implicated in the rising prevalence of obesity and diet-related chronic diseases worldwide. However, little is known about their contribution to weight gain in Asian populations. This study aimed to investigate weight change associated with SSB consumption between 2005 and 2009 in a large national cohort of Thai university students.

Methods

Questionnaire data were collected from a large Thai cohort (the Thai Health-Risk Transition: a National Cohort Study). The analysis was based on responses from 59 283 of the 60 569 (98%) cohort members who had valid SSB consumption and weight variables in 2005 and 2009. The relationship between SSB consumption in 2005 and self-reported weight change was analysed using multiple linear regression models controlled for socio-demographic, activity and (non-validated) dietary factors shown to influence weight.

Results

Higher frequency of SSB consumption in 2005 was significantly associated with greater weight gain between 2005 and 2009 in all age groups and in both sexes (p<0.0001); persons who consumed SSBs at least once a day in 2005 gained 0.5 kg more than those who consumed SSBs less than once a month. The estimated weight gain for the average person in the sample was 1.9 kg (95% C I 1.95–1.96). The difference in weight gain between those who increased their consumption frequency (<once a month to > once per day) between 2005 and 2009 compared to those who maintained it was 0.3 kgs, while persons who reduced their consumption frequency (once a day to > once a month) gained 0.2 kgs less than those whose consumption remained unchanged.

Conclusion

SSB consumption is independently associated with weight gain in the Thai population. Research and health promotion in Thailand and other economically transitioning countries should focus on reducing their contribution to population weight gain and to diet-related chronic diseases.     

Cognitive Distance,Absorptive Capacity and Group Rationality: A Simulation Study

We report the results of a simulation study in which we explore the joint effect of group absorptive capacity (as the average individual rationality of the group members) and cognitive distance (as the distance between the most rational group member and the rest of the group) on the emergence of collective rationality in groups. We start from empirical results reported in the literature on group rationality as collective group level competence and use data on real-life groups of four and five to validate a mathematical model. We then use this mathematical model to predict group level scores from a variety of possible group configurations (varying both in cognitive distance and average individual rationality). Our results show that both group competence and cognitive distance are necessary conditions for emergent group rationality. Group configurations, in which the groups become more rational than the most rational group member, are groups scoring low on cognitive distance and scoring high on absorptive capacity.