Machine learning differentiates enzymatic and non-enzymatic metals in proteins

Metalloenzymes are 40% of all enzymes and can perform all seven classes of enzyme reactions. Because of the physicochemical similarities between the active sites of metalloenzymes and inactive metal binding sites, it is challenging to differentiate between them. Yet distinguishing these two classes is critical for the identification of both native and designed enzymes. Because of similarities between catalytic and non-catalytic metal binding sites, finding physicochemical features that distinguish these two types of metal sites can indicate aspects that are critical to enzyme function. In this work, we develop the largest structural dataset of enzymatic and non-enzymatic metalloprotein sites to date. We then use a decision-tree ensemble machine learning model to classify metals bound to proteins as enzymatic or non-enzymatic with 92.2% precision and 90.1% recall. Our model scores electrostatic and pocket lining features as more important than pocket volume, despite the fact that volume is the most quantitatively different feature between enzyme and non-enzymatic sites. Finally, we find our model has overall better performance in a side-to-side comparison against other methods that differentiate enzymatic from non-enzymatic sequences. We anticipate that our model’s ability to correctly identify which metal sites are responsible for enzymatic activity could enable identification of new enzymatic mechanisms and de novo enzyme design

Efflux Pumps Represent Possible Evolutionary Convergence onto the Beta Barrel Fold

Preprint now published in Structure doi: 10.1016/j.str.2018.06.007There are around 100 types of integral outer membrane proteins in each Gram negative bacteria. All of these proteins have the same fold—an up-down β-barrel. It has been suggested that all membrane β-barrels other than lysins are homologous. Here we suggest that β-barrels of efflux pumps have converged on this fold as well. By grouping structurally-solved outer membrane β-barrels (OMBBs) by sequence we find evidence that the membrane environment may have led to convergent evolution of the barrel fold. Specifically, the lack of sequence linkage to other barrels coupled with distinctive structural differences, such as differences in strand tilt and barrel radius, suggest that efflux pumps have evolutionarily converged on the barrel. Finally, we find a possible ancestor for the OMBB efflux pumps as they are related to periplasmic components of the same pumps

Fracture in the Elderly Multidisciplinary Rehabilitation (FEMuR): study protocol for a phase II randomised feasibility study of a multidisciplinary rehabilitation package following hip fracture

Objective: To conduct a rigorous feasibility study for a future definitive parallel-group randomised controlled trial (RCT) and economic evaluation of an enhanced rehabilitation package for hip fracture.Setting: Recruitment from 3 acute hospitals in North Wales. Intervention delivery in the community.Participants: Older adults (aged ≥65) who received surgical treatment for hip fracture, lived independently prior to fracture, had mental capacity (assessed by clinical team) and received rehabilitation in the North Wales area.Intervention: Remote randomisation to usual care (control) or usual care+enhanced rehabilitation package (intervention), including six additional home-based physiotherapy sessions delivered by a physiotherapist or technical instructor, novel information workbook and goal-setting diary.Primary and secondary outcome measures: Primary: Barthel Activities of Daily Living (BADL). Secondary measures included Nottingham Extended Activities of Daily Living scale (NEADL), EQ-5D, ICECAP capability, a suite of self-efficacy, psychosocial and service-use measures and costs. Outcome measures were assessed at baseline and 3-month follow-up by blinded researchers.Results: 62 participants were recruited, 61 randomised (control 32; intervention 29) and 49 (79%) completed 3-month follow-up. Minimal differences occurred between the 2 groups for most outcomes, including BADL (adjusted mean difference 0.5). The intervention group showed a medium-sized improvement in the NEADL relative to the control group, with an adjusted mean difference between groups of 3.0 (Cohen's d 0.63), and a trend for greater improvement in self-efficacy and mental health, but with small effect sizes. The mean cost of delivering the intervention was £231 per patient. There was a small relative improvement in quality-adjusted life year in the intervention group. No serious adverse events relating to the intervention were reported.Conclusions: The trial methods were feasible in terms of eligibility, recruitment and retention. The effectiveness and cost-effectiveness of the rehabilitation package should be tested in a phase III RCT

The physical, economic and policy drivers of land conversion to forestry in Ireland

peer-reviewedLand use change is fundamentally a product of the interaction of physical land characteristics, economic considerations and agricultural and environmental policies. Researchers are increasingly combining physical and socio-economic spatial data to investigate the drivers of land-use change in relation to policy and economic developments. Focusing on Ireland, this study develops a panel data set of annual afforestation over 2811 small-area boundaries between 1993 and 2007 from vector and raster data sources. Soil type and other physical characteristics are combined with the net returns of converting agricultural land to forestry, based on the micro-simulation of individual farm incomes, to investigate land conversion. A spatial econometric approach is adopted to model the data and a range of physical, economic and policy factors are identified as having a significant effect on afforestation rates. In addition to the financial returns, the availability and quality of land and the implementation of environmental protection policies are identified as important factors in land conversion. The implications of these factors for the goal of forest expansion are discussed in relation to conflicting current and future land use policies.Department of Agriculture, Food and the Marin

Can we improve cognitive function among adults with osteoarthritis by increasing moderate-to-vigorous physical activity and reducing sedentary behaviour? Secondary analysis of the MONITOR-OA study

Background: Preliminary evidence suggests osteoarthritis is a risk factor for cognitive decline. One potential reason is 87% of adults with osteoarthritis are inactive, and low moderate-to-vigorous physical activity and high sedentary behaviour are each risk factors for cognitive decline. Thus, we investigated whether a community-based intervention to increase moderate-to-vigorous physical activity and reduce sedentary behaviour could improve cognitive function among adults with osteoarthritis. Methods: This was a secondary analysis of a six month, proof-of-concept randomized controlled trial of a community-based, technology-enabled counselling program to increase moderate-to-vigorous physical activity and reduce sedentary behaviour among adults with knee osteoarthritis. The Immediate Intervention (n = 30) received a Fitbit® Flex™ and four bi-weekly activity counselling sessions; the Delayed Intervention (n = 31) received the same intervention two months later. We assessed episodic memory and working memory using the National Institutes of Health Toolbox Cognition Battery. Between-group differences (Immediate Intervention vs. Delayed Intervention) in cognitive performance were evaluated following the primary intervention (i.e., Baseline – 2 Months) using intention-to-treat. Results: The intervention did not significantly improve cognitive function; however, we estimated small average improvements in episodic memory for the Immediate Intervention vs. Delayed Intervention (estimated mean difference: 1.27; 95% CI [− 9.27, 11.81]; d = 0.10). Conclusion: This small study did not show that a short activity promotion intervention improved cognitive health among adults with osteoarthritis. However, the effects of increased moderate-to-vigorous physical activity and reduced sedentary behaviour are likely to be small and thus we recommend subsequent studies use larger sample sizes and measure changes in cognitive function over longer intervals. Trial registration number: ClinicalTrials.gov Protocol Registration System: NCT02315664 ; registered 12 December, 2014; https://clinicaltrials.gov/ct2/show/NCT02315664?cond=NCT02315664&rank=1Medicine, Faculty ofOther UBCPhysical Therapy, Department ofReviewedFacult