A Blind Test of Computational Technique for Predicting the Likelihood of Peptide Sequences to Cyclize

An in silico computational technique for predicting peptide sequences that can be cyclized by cyanobactin macrocyclases, e.g., PatGmac, is reported. We demonstrate that the propensity for PatGmac-mediated cyclization correlates strongly with the free energy of the so-called pre-cyclization conformation (PCC), which is a fold where the cyclizing sequence C and N termini are in close proximity. This conclusion is driven by comparison of the predictions of boxed molecular dynamics (BXD) with experimental data, which have achieved an accuracy of 84%. A true blind test rather than training of the model is reported here as the in silico tool was developed before any experimental data was given, and no parameters of computations were adjusted to fit the data. The success of the blind test provides fundamental understanding of the molecular mechanism of cyclization by cyanobactin macrocyclases, suggesting that formation of PCC is the rate-determining step. PCC formation might also play a part in other processes of cyclic peptides production and on the practical side the suggested tool might become useful for finding cyclizable peptide sequences in general

Warm Water and Cool Nests Are Best. How Global Warming Might Influence Hatchling Green Turtle Swimming Performance

For sea turtles nesting on beaches surrounded by coral reefs, the most important element of hatchling recruitment is escaping predation by fish as they swim across the fringing reef, and as a consequence hatchlings that minimize their exposure to fish predation by minimizing the time spent crossing the fringing reef have a greater chance of surviving the reef crossing. One way to decrease the time required to cross the fringing reef is to maximize swimming speed. We found that both water temperature and nest temperature influence swimming performance of hatchling green turtles, but in opposite directions. Warm water increases swimming ability, with hatchling turtles swimming in warm water having a faster stroke rate, while an increase in nest temperature decreases swimming ability with hatchlings from warm nests producing less thrust per stroke

A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: A multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking

AbstractPurposeA study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion.Methods and materialsTen institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded.ResultsFor all lung traces all measurement sets show improved dose accuracy with a mean 2%/2mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p<0.001). For all prostate the mean 2%/2mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p<0.001). The difference between the four systems was small with an average 2%/2mm γ-fail rate of <3% for all systems with adaptation for lung and prostate.ConclusionsThe investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods

Are ethnic disparities in HbA1c levels explained by mental wellbeing? Analysis of population-based data from the Health Survey for England

Aims: It is unclear how ethnic differences in HbA1c levels are affected by individual variations in mental wellbeing. Thus, the aim of this study was to assess the extent to which HbA1c disparities between Caucasian and South Asian adults are mediated by various aspects of positive psychological functioning. Methods: Data from the 2014 Health Survey for England was analysed using bootstrapping methods. A total of 3894 UK residents with HbA1c data were eligible to participate. Mental wellbeing was assessed using the Warwick-Edinburgh Mental Well-Being Scale. To reduce bias BMI, blood pressure, diabetes status, and other factors were treated as covariates. Results: Ethnicity directly predicted blood sugar control (unadjusted coefficient -2.15; 95% CI -3.64, -0.67), with Caucasians generating lower average HbA1c levels (37.68 mmol/mol (5.6%)) compared to South Asians (39.87 mmol/mol (5.8%)). This association was mediated by positive mental wellbeing, specifically concerning perceived vigour (unadjusted effect 0.30; 95% CI 0.13, 0.58): South Asians felt more energetic than Caucasians (unadjusted coefficient -0.32; 95% CI -0.49, -0.16), and greater perceived energy predicted lower HbA1c levels (unadjusted coefficient -0.92; 95% CI -1.29, -0.55). This mediator effect accounted for just over 14% of the HbA1c variance, and was negated after adjusting for BMI. Conclusions: Caucasian experience better HbA1c levels compared with their South Asian counterparts. However, this association is partly confounded by individual differences in perceived energy levels, which is implicated in better glycaemic control, and appears to serve a protective function in South Asians

The relationship between childhood body weight and dental caries experience:an umbrella systematic review protocol

Abstract Background Obesity and dental caries are global public health problems which can impact in childhood and throughout the life course. In simple terms, childhood dental caries and body weight are linked via the common risk factor of diet. An association between dental caries and obesity has been described in a number of studies and reviews. However, similarly, a relationship has also been noted between low body weight and caries experience in children. This protocol will provide the framework for an umbrella review to address the following question: Does the available evidence support a relationship between dental caries experience and body weight in the child population? Methods This review protocol outlines the process to carry out an umbrella systematic review which will synthesise previous reviews of childhood dental caries experience and body weight. An umbrella review methodology will be used to examine the methodological and reporting quality of existing reviews. Discussion The final umbrella review aims to aggregate the available evidence in order to provide a summary for policymakers and to inform healthcare interventions. Systematic review registration PROSPERO CRD4201604730

Perceived barriers and enablers of physical activity in postpartum women: A qualitative approach

© 2016 Saligheh et al.Background: Postpartum women's recovery from birth can be assisted through increased physical activity (PA). However, women face substantial barriers to participating in exercise and require support to enable them to benefit from increased PA. Methods: This study sought to explore women's beliefs about and experiences of PA and exercise during the 6 weeks to 12 months postpartum period. A cohort of 14 postpartum women from a survey study of the barriers and enablers to exercise participation agreed to take part in interview sessions to provide an in-depth understanding of the women's perceptions of the postpartum period and their physical activity during this time. Results: Findings are presented with reference to the social ecological framework and indicate postpartum women face substantial personal and environmental barriers to PA and exercise participation: fatigue, a lack of motivation and confidence, substantial time constraints, lack of access to affordable and appropriate activities and poor access to public transport. In contrast, enablers such as possessing greater social support, in particular partner support, improved PA and exercise participation. Conclusions: The findings encourage facilitation of exercise through mothers' groups, mothers' exercise clubs or postnatal classes suggesting behavioral and social change is needed. Interaction between individuals, community, organizations and policy makers is required. In addition, the provision of specifically tailored and appropriate exercise programs could potentially enable increased PA in postpartum women, thereby improving their health

Recurring alcohol-related care between 1998 and 2007 among people treated for an alcohol-related disorder in 1997: A register study in Stockholm County

<p>Abstract</p> <p>Background</p> <p>Inpatient care for alcohol intoxication is increasing in Sweden, especially among young women. Since it is well known that alcohol disorder is a chronic relapsing illness, this study examines the extent to which people return for more care.</p> <p>Method</p> <p>All inpatients with alcohol-related diagnoses in Stockholm County during 1997 were followed prospectively to 2007 through registers. The proportion reappearing for the same diagnosis, other alcohol-related inpatient, or outpatient care each year after baseline, as well as the number of years the inpatients reappeared were calculated (n = 2735). Three diagnoses were examined separately; alcohol dependence, harmful use of alcohol, and alcohol intoxication.</p> <p>Results</p> <p>Three out of five inpatients with an alcohol diagnoses reappeared for more alcohol-related inpatient care during the following decade. The proportion returning was largest the year after baseline and then decreased curvilinearly over time. The inclusion of outpatient care increased proportions, but did not change patterns. Of those with an alcohol dependence diagnosis at baseline 42 percent returned for more alcohol-related inpatient care the first, 28 percent the fifth, and 25 percent the tenth year. Corresponding proportions for harmful use and intoxication were smaller. One in five among those with an alcohol dependence returned for more than five of the ten years. Ordered logistic regressions confirmed that besides diagnosis, age and gender were independently related to the number of years returning to care.</p> <p>Conclusions</p> <p>While middle-aged males with alcohol dependence were in a revolving door, young female inpatients with intoxication diagnosis returned to a comparably lower degree.</p

A closer look at neuron interaction with track-etched microporous membranes

Microporous membranes support the growth of neurites into and through micro-channels, providing a different type of neural growth platform to conventional dish cultures. Microporous membranes are used to support various types of culture, however, the role of pore diameter in relation to neurite growth through the membrane has not been well characterised. In this study, the human cell line (SH-SY5Y) was differentiated into neuron-like cells and cultured on track-etched microporous membranes with pore and channel diameters selected to accommodate neurite width (0.8 µm to 5 µm). Whilst neurites extended through all pore diameters, the extent of neurite coverage on the non-seeded side of the membranes after 5 days in culture was found to be directly proportional to channel diameter. Neurite growth through membrane pores reduced significantly when neural cultures were non-confluent. Scanning electron microscopy revealed that neurites bridged pores and circumnavigated pore edges – such that the overall likelihood of a neurite entering a pore channel was decreased. These findings highlight the role of pore diameter, cell sheet confluence and contact guidance in directing neurite growth through pores and may be useful in applications that seek to use physical substrates to maintain separate neural populations whilst permitting neurite contact between cultures

Search for ZZ and ZW Production in ppbar Collisions at sqrt(s) = 1.96 TeV

We present a search for ZZ and ZW vector boson pair production in ppbar collisions at sqrt(s) = 1.96 TeV using the leptonic decay channels ZZ --> ll nu nu, ZZ --> l l l' l' and ZW --> l l l' nu. In a data sample corresponding to an integrated luminosity of 194 pb-1 collected with the Collider Detector at Fermilab, 3 candidate events are found with an expected background of 1.0 +/- 0.2 events. We set a 95% confidence level upper limit of 15.2 pb on the cross section for ZZ plus ZW production, compared to the standard model prediction of 5.0 +/- 0.4 pb.Comment: 7 pages, 2 figures. This version is accepted for publication by Phys. Rev. D Rapid Communication