Parallel compensatory evolution stabilizes plasmids across the parasitism-mutualism continuum

Plasmids drive genomic diversity in bacteria via horizontal gene transfer [1 and 2]; nevertheless, explaining their survival in bacterial populations is challenging [3]. Theory predicts that irrespective of their net fitness effects, plasmids should be lost: when parasitic (costs outweigh benefits), plasmids should decline due to purifying selection [4, 5 and 6], yet under mutualism (benefits outweigh costs), selection favors the capture of beneficial accessory genes by the chromosome and loss of the costly plasmid backbone [4]. While compensatory evolution can enhance plasmid stability within populations [7, 8, 9, 10, 11, 12, 13, 14 and 15], the propensity for this to occur across the parasitism-mutualism continuum is unknown. We experimentally evolved Pseudomonas fluorescens and its mercury resistance mega-plasmid, pQBR103 [ 16], across an environment-mediated parasitism-mutualism continuum. Compensatory evolution stabilized plasmids by rapidly ameliorating the cost of plasmid carriage in all environments. Genomic analysis revealed that, in both parasitic and mutualistic treatments, evolution repeatedly targeted the gacA/gacS bacterial two-component global regulatory system while leaving the plasmid sequence intact. Deletion of either gacA or gacS was sufficient to completely ameliorate the cost of plasmid carriage. Mutation of gacA/gacS downregulated the expression of ∼17% of chromosomal and plasmid genes and appears to have relieved the translational demand imposed by the plasmid. Chromosomal capture of mercury resistance accompanied by plasmid loss occurred throughout the experiment but very rarely invaded to high frequency, suggesting that rapid compensatory evolution can limit this process. Compensatory evolution can explain the widespread occurrence of plasmids and allows bacteria to retain horizontally acquired plasmids even in environments where their accessory genes are not immediately useful

Rapid compensatory evolution promotes the survival of conjugative plasmids

Conjugative plasmids play a vital role in bacterial adaptation through horizontal gene transfer. Explaining how plasmids persist in host populations however is difficult, given the high costs often associated with plasmid carriage. Compensatory evolution to ameliorate this cost can rescue plasmids from extinction. In a recently published study we showed that compensatory evolution repeatedly targeted the same bacterial regulatory system, GacA/GacS, in populations of plasmid-carrying bacteria evolving across a range of selective environments. Mutations in these genes arose rapidly and completely eliminated the cost of plasmid carriage. Here we extend our analysis using an individual based model to explore the dynamics of compensatory evolution in this system. We show that mutations which ameliorate the cost of plasmid carriage can prevent both the loss of plasmids from the population and the fixation of accessory traits on the bacterial chromosome. We discuss how dependent the outcome of compensatory evolution is on the strength and availability of such mutations and the rate at which beneficial accessory traits integrate on the host chromosome

Ironless wheel motor for a direct drive vehicle application

An ironless motor for use as direct wheel drive is presented. The motor is intended for use in a lightweight (600kg), low drag, series hybrid commuter vehicle under development at The University of Queensland. The vehicle will utilise these ironless motors in each of its rear wheels, with each motor producing a peak torque output of 500Nm and a maximum rotational speed of 1500rpm. The axial flux motor consists of twin Ironless litz wire stators with a central magnetic ring and simplified Halbach magnet arrays on either side. A small amount of iron is used to support the outer Halbach arrays and to improve the peak magnetic flux density. Ducted air cooling is used to remove heat from the motor and will allow for a continuous torque rating of 250Nm. Ironless machines have previously been shown to be effective in high speed, high frequency applications (+1000Hz). They are generally regarded as non-optimal for low speed applications as iron cores allow for better magnet utilisation and do not significantly increase the weight of a machine. However, ironless machines can also be seen to be effective in applications where the average torque requirement is much lower than the peak torque requirement such as in some vehicle drive applications. The low spinning losses in ironless machines are shown to result in very high energy throughput efficiency in a wide range of vehicle driving cycles

The UltraCommuter : a viable and desirable solar-powered commuter vehicle

The University of Queensland UltraCommuter project is the demonstration of an ultra-light weight, low drag, energy efficient and low polluting, electric commuter vehicle equipped with a 2.5m2 on-board solar array. A key goal of the project is to make the vehicle predominantly self-sufficient from solar power for normal driving purposes , so that it does not require charging or refuelling from off-board sources. This paper examines the technical feasibility of the solar-powered commuter vehicle concept, as it applies the UltraCommuter project. A parametric description of a solar-powered commuter vehicle is presented. Real solar insolation data is then used to predict the solar driving range for the UltraCommuter and this is compared to typical urban usage patterns for commuter vehicles in Queensland. A comparative analysis of annual greenhouse gas emissions from the vehicle is also presented. The results show that the UltraCommuter’s on-board solar array can provide substantial supplementation of the energy required for normal driving, powering 90% of annual travel needs for an average QLD passenger vehicle. The vehicle also has excellent potential to reduce annual greenhouse gas emissions from the private transport sector, achieving a 98% reduction in CO2 emissions when compared to the average QLD passenger vehicle. Lastly, the vehicle battery pack provides for tolerance to consecutive days of poor weather without resorting to grid charging, giving uninterrupted functionality to the user. These results hold great promise for the technical feasibility of the solar-powered commuter vehicle concept

A new approach to estimation of global air-sea gas transfer velocity fields using dual-frequency altimeter backscatter

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 112 (2007): C11003, doi:10.1029/2006JC003819.A new approach to estimating air-sea gas transfer velocities based on normalized backscatter from the dual-frequency TOPEX and Jason-1 altimeters is described. The differential scattering of Ku-band (13.6 GHz) and C-band (5.3 GHz) microwave pulses is used to isolate the contribution of small-scale waves to mean square slope and gas transfer. Mean square slope is derived for the nominal wave number range 40–100 rad m−1 by differencing mean square slope estimates computed from the normalized backscatter in each band, using a simple geometric optics model. Model parameters for calculating the differenced mean square slope over this wave number range are optimized using in situ optical slope measurements. An empirical relation between gas transfer velocity and mean square slope, also based on field measurements, is then used to derive gas transfer velocities. Initial results demonstrate that the calculated transfer velocities exhibit magnitudes and a dynamic range which are generally consistent with existing field measurements. The new algorithm is used to construct monthly global maps of gas transfer velocity and to illustrate seasonal transfer velocity variations over a 1-year period. The measurement precision estimated from >106 duplicate observations of the sea surface by TOPEX and Jason-1 altimeters orbiting in tandem is better than 10%. The estimated overall uncertainty of the method is ±30%. The long-term global, area-weighted, Schmidt number corrected, mean gas transfer velocity is 13.7 ± 4.1 cm h−1. The new approach, based on surface roughness, represents a potential alternative to commonly used parameterizations based on wind speed.Financial support for this research from the National Aeronautics and Space Administration through Jet Propulsion Laboratory contract 961425 and the NOAA Global Carbon Cycle Program under grant NA16GP2918, Office of Global Programs is gratefully acknowledged

Identification of a Rare Coding Variant in Complement 3 Associated with Age-related Macular Degeneration

Macular degeneration is a common cause of blindness in the elderly. To identify rare coding variants associated with a large increase in risk of age-related macular degeneration (AMD), we sequenced 2,335 cases and 789 controls in 10 candidate loci (57 genes). To increase power, we augmented our control set with ancestry-matched exome sequenced controls. An analysis of coding variation in 2,268 AMD cases and 2,268 ancestry matched controls revealed two large-effect rare variants; previously described R1210C in the CFH gene (fcase = 0.51%, fcontrol = 0.02%, OR = 23.11), and newly identified K155Q in the C3 gene (fcase = 1.06%, fcontrol = 0.39%, OR = 2.68). The variants suggest decreased inhibition of C3 by Factor H, resulting in increased activation of the alternative complement pathway, as a key component of disease biology

An assessment of prevalence of Type 1 CFI rare variants in European AMD, and why lack of broader genetic data hinders development of new treatments and healthcare access

PurposeAdvanced age-related macular degeneration (AAMD) risk is associated with rare complement Factor I (FI) genetic variants associated with low FI protein levels (termed ‘Type 1’), but it is unclear how variant prevalences differ between AMD patients from different ethnicities.MethodsCollective prevalence of Type 1 CFI rare variant genotypes were examined in four European AAMD datasets. Collective minor allele frequencies (MAFs) were sourced from the natural history study SCOPE, the UK Biobank, the International AMD Genomics Consortium (IAMDGC), and the Finnish Biobank Cooperative (FINBB), and compared to paired control MAFs or background population prevalence rates from the Genome Aggregation Database (gnomAD). Due to a lack of available genetic data in non-European AAMD, power calculations were undertaken to estimate the AAMD population sizes required to identify statistically significant association between Type 1 CFI rare variants and disease risk in different ethnicities, using gnomAD populations as controls.ResultsType 1 CFI rare variants were enriched in all European AAMD cohorts, with odds ratios (ORs) ranging between 3.1 and 7.8, and a greater enrichment was observed in dry AMD from FINBB (OR 8.9, 95% CI 1.49–53.31). The lack of available non-European AAMD datasets prevented us exploring this relationship more globally, however a statistical association may be detectable by future sequencing studies that sample approximately 2,000 AAMD individuals from Ashkenazi Jewish and Latino/Admixed American ethnicities.ConclusionsThe relationship between Type 1 CFI rare variants increasing odds of AAMD are well established in Europeans, however the lack of broader genetic data in AAMD has adverse implications for clinical development and future commercialisation strategies of targeted FI therapies in AAMD. These findings emphasise the importance of generating more diverse genetic data in AAMD to improve equity of access to new treatments and address the bias in health care.</p

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Biochemical and physiological investigations of the activities of TorD family chaperones in Escherichia coli and Salmonella enterica serovar Typhimurium

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The development of a screening questionnaire for childhood cruelty to animals

Childhood cruelty to animals may be a marker of poor prognosis amongst conduct disordered children. However, other than semistructured interviews with parents or children, there are no screening instruments for this behavior. The aim of this study was to develop such an instrument. In the first phase of the study, a parent-report questionnaire, Children\u27s Attitudes and Behaviors Towards Animals (CABTA) was designed and piloted on 360 elementary school children, enabling community norms and a factor structure for the instrument to be derived. In the second phase, the questionnaire was completed by the parents of a small sample of children (N= 17) to establish its test-retest reliability. In the third phase of the study, the CABTA was completed by the parents of 19 children who had been diagnosed with either a Disruptive Behavioral Disorder or Attention Deficit Hyperactivity Disorder, and the results were compared with the outcome of a semistructured interview with parents regarding their child\u27s behavior toward animals. The results of the various phases of the study indicated that the CABTA consists of two factors, Typical and Malicious Cruelty to animals, and is a reliable and valid tool for detecting childhood cruelty to animals. Possible use and adaptations of the CABTA as a screening instrument in clinical and community samples are discussed.<br /