Measuring rainfall from above and below the sea surface

Satellites play a major role in the determination of the rainfall at sea. Researchers at Southampton Oceanography Centre (SOC) have been involved in two projects addressing this task. First they have been instrumental in developing techniques to retrieve rain rate information from the 10+ years of dual-frequency altimeter data. The TOPEX radar measures rainfall via the attenuation it causes, producing a climatology that is independent of those derived from passive microwave (PM) and infrared (IR) sensors. Because TOPEX is an active microwave sensor, it can have a much smaller footprint than PM sensors. Therefore it can be used to estimate the size of rain cells, showing that the ITCZ and mid-latitude storm tracks are characterized by larger rain systems than elsewhere. TOPEX’s simultaneous recording of wind and wave data reveal that, for mid-latitude systems, rain is most likely in association with developing seas.All satellite-based datasets require validation, and SOC's work on the development and testing of acoustic rain gauges is the second aspect of this paper. By listening at a range of frequencies, an underwater hydrophone may distinguish the spectra of wind, rain, shipping etc., and estimate the wind speed or rain rate according to the magnitude of the signals. All our campaigns have shown a good acoustic response to changes in wind speed. However the quantitative inversion for recent trials has given values that are too high, possibly because of significant acoustic reflection from the sea bottom. The changes in spectral slope often agree with other observations of rain, although validation experiments in coastal regions are hampered by the extraneous sources present. Acoustic rain gauges would eventually see service not only for routine satellite validation, but also for real-time monitoring of locations of interest

Weathering the storm: developments in the acoustic sensing of wind and rain

An Acoustic Rain Gauge (ARG) analyses the underwater sound levels across a wide frequency range, classifies the observed spectrum according to likely source and then determines the local wind speed or rain rate as appropriate. Thispaper covers a trial on the Scotian Shelf off Canada, comparing the geophysical information derived from the acoustic signals with those obtained from other sources

Visual impairment as a function of visual acuity in both eyes and its impact on patient reported preferences

10.1371/journal.pone.0081042PLoS ONE812-POLN

Extremely fast amelioration of plasmid fitness costs by multiple functionally diverse pathways

The acquisition of plasmids is often accompanied by fitness costs such that compensatory evolution is required to allow plasmid survival, but it is unclear whether compensatory evolution can be extensive or rapid enough to maintain plasmids when they are very costly. The mercury-resistance plasmid pQBR55 drastically reduced the growth of its host, Pseudomonas fluorescens SBW25, immediately after acquisition, causing a small colony phenotype. However, within 48 h of growth on agar plates we observed restoration of the ancestral large colony morphology, suggesting that compensatory mutations had occurred. Relative fitness of these evolved strains, in lab media and in soil microcosms, varied between replicates, indicating different mutational mechanisms. Using genome sequencing we identified that restoration was associated with chromosomal mutations in either a hypothetical DNA-binding protein PFLU4242, RNA polymerase or the GacA/S two-component system. Targeted deletions in PFLU4242, gacA or gacS recapitulated the ameliorated phenotype upon plasmid acquisition, indicating three distinct mutational pathways to compensation. Our data shows that plasmid compensatory evolution is fast enough to allow survival of a plasmid despite it imposing very high fitness costs upon its host, and indeed may regularly occur during the process of isolating and selecting individual plasmid-containing clones

Positive selection inhibits plasmid coexistence in bacterial genomes

Plasmids play an important role in bacterial evolution by transferring niche-adaptive functional genes between lineages, thus driving genomic diversification. Bacterial genomes commonly contain multiple, coexisting plasmid replicons, which could fuel adaptation by increasing the range of gene functions available to selection and allowing their recombination. However, plasmid coexistence is difficult to explain because the acquisition of plasmids typically incurs high fitness costs for the host cell. Here, we show that plasmid coexistence was stably maintained without positive selection for plasmid-borne gene functions and was associated with compensatory evolution to reduce fitness costs. In contrast, with positive selection, plasmid coexistence was unstable despite compensatory evolution. Positive selection discriminated between differential fitness benefits of functionally redundant plasmid replicons, retaining only the more beneficial plasmid. These data suggest that while the efficiency of negative selection against plasmid fitness costs declines over time due to compensatory evolution, positive selection to maximize plasmid-derived fitness benefits remains efficient. Our findings help to explain the forces structuring bacterial genomes: coexistence of multiple plasmids in a genome is likely to require either rare positive selection in nature or nonredundancy of accessory gene functions among the coexisting plasmids

Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration

BACKGROUND: HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: OBJECTIVES: To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes. DESIGN: A proof of concept double-masked randomized controlled study. PARTICIPANTS: 114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA ≥ 20/60 in at least one eye, and a normal lipid profile. INTERVENTION: Simvastatin 40 mg/day or placebo, allocated 1:1. MAIN OUTCOME MEASURES: Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18-0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27-3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07-0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02-0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected. CONCLUSION/SIGNIFICANCE: Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065

Recurrent structural variation, clustered sites of selection, and disease risk for the complement factor H (CFH) gene family

Data deposition: The data reported in this paper have been deposited as a National Center for Biotechnology Information BioProject (accession no. PRJNA401648). Author contributions: S.C. and E.E.E. designed research; S.C., C.B., L.H., K.P., K.M.M., M.S., A.E.W., V.D., T.A.G.-L., and R.K.W. performed research; S.C., J.H., C.B., L.H., K.P., K.M.M., M.S., A.E.W., V.D., F.G., A.J.R., R.H.G., T.A.G.-L., R.K.W., B.H.F.W., P.N.B., R.A., and E.E.E. contributed new reagents/analytic tools; S.C., B.J.N., J.H., and E.E.E. analyzed data; and S.C., B.J.N., and E.E.E. wrote the paper.Peer reviewedPublisher PD

Quantitative bone marrow lesion size in osteoarthritic knees correlates with cartilage damage and predicts longitudinal cartilage loss

<p>Abstract</p> <p>Background</p> <p>Bone marrow lesions (BMLs), common osteoarthritis-related magnetic resonance imaging findings, are associated with osteoarthritis progression and pain. However, there are no articles describing the use of 3-dimensional quantitative assessments to explore the longitudinal relationship between BMLs and hyaline cartilage loss. The purpose of this study was to assess the cross-sectional and longitudinal descriptive characteristics of BMLs with a simple measurement of approximate BML volume, and describe the cross-sectional and longitudinal relationships between BML size and the extent of hyaline cartilage damage.</p> <p>Methods</p> <p>107 participants with baseline and 24-month follow-up magnetic resonance images from a clinical trial were included with symptomatic knee osteoarthritis. An 'index' compartment was identified for each knee defined as the tibiofemoral compartment with greater disease severity. Subsequently, each knee was evaluated in four regions: index femur, index tibia, non-index femur, and non-index tibia. Approximate BML volume, the product of three linear measurements, was calculated for each BML within a region. Cartilage parameters in the index tibia and femur were measured based on manual segmentation.</p> <p>Results</p> <p>BML volume changes by region were: index femur (median [95% confidence interval of the median]) 0.1 cm³(-0.5 to 0.9 cm³), index tibia 0.5 cm³(-0.3 to 1.7 cm³), non-index femur 0.4 cm³(-0.2 to 1.6 cm³), and non-index tibia 0.2 cm³(-0.1 to 1.2 cm³). Among 44 knees with full thickness cartilage loss, baseline tibia BML volume correlated with baseline tibia full thickness cartilage lesion area (<it>r </it>= 0.63, <it>p</it>< 0.002) and baseline femur BML volume with longitudinal change in femoral full thickness cartilage lesion area (<it>r </it>= 0.48 <it>p</it>< 0.002).</p> <p>Conclusions</p> <p>Many regions had no or small longitudinal changes in approximate BML volume but some knees experienced large changes. Baseline BML size was associated to longitudinal changes in area of full thickness cartilage loss.</p

The Hydrophobic Core of Twin-Arginine Signal Sequences Orchestrates Specific Binding to Tat-Pathway Related Chaperones

Redox enzyme maturation proteins (REMPs) bind pre-proteins destined for translocation across the bacterial cytoplasmic membrane via the twin-arginine translocation system and enable the enzymatic incorporation of complex cofactors. Most REMPs recognize one specific pre-protein. The recognition site usually resides in the N-terminal signal sequence. REMP binding protects signal peptides against degradation by proteases. REMPs are also believed to prevent binding of immature pre-proteins to the translocon. The main aim of this work was to better understand the interaction between REMPs and substrate signal sequences. Two REMPs were investigated: DmsD (specific for dimethylsulfoxide reductase, DmsA) and TorD (specific for trimethylamine N-oxide reductase, TorA). Green fluorescent protein (GFP) was genetically fused behind the signal sequences of TorA and DmsA. This ensures native behavior of the respective signal sequence and excludes any effects mediated by the mature domain of the pre-protein. Surface plasmon resonance analysis revealed that these chimeric pre-proteins specifically bind to the cognate REMP. Furthermore, the region of the signal sequence that is responsible for specific binding to the corresponding REMP was identified by creating region-swapped chimeric signal sequences, containing parts of both the TorA and DmsA signal sequences. Surprisingly, specificity is not encoded in the highly variable positively charged N-terminal region of the signal sequence, but in the more similar hydrophobic C-terminal parts. Interestingly, binding of DmsD to its model substrate reduced membrane binding of the pre-protein. This property could link REMP-signal peptide binding to its reported proofreading function