Novel DNA methylation profiles associated with key gene regulation and transcription pathways in blood and placenta of growth-restricted neonates

BB/H012494/1/ Biotechnology and Biological Sciences Research Counci

Force-Velocity Relations of a Two-State Crossbridge Model for Molecular Motors

We discuss the force-velocity relations obtained in a two-state crossbridge model for molecular motors. They can be calculated analytically in two limiting cases: for a large number and for one pair of motors. The effect of the strain-dependent detachment rate on the motor characteristics is studied. It can lead to linear, myosin-like, kinesin-like and anomalous curves. In particular, we specify the conditions under which oscillatory behavior may be found.Comment: 5 pages, 4 figures, REVTeX; thoroughly revised version; also available at http://www.physik.tu-muenchen.de/~frey

Fluctuating-friction molecular motors

We show that the correlated stochastic fluctuation of the friction coefficient can give rise to long-range directional motion of a particle undergoing Brownian random walk in a constant periodic energy potential landscape. The occurrence of this motion requires the presence of two additional independent bodies interacting with the particle via friction and via the energy potential, respectively, which can move relative to each other. Such three-body system generalizes the classical Brownian ratchet mechanism, which requires only two interacting bodies. In particular, we describe a simple two-level model of fluctuating-friction molecular motor that can be solved analytically. In our previous work [M.K., L.M and D.P. 2000 J. Nonlinear Opt. Phys. Mater. vol. 9, 157] this model has been first applied to understanding the fundamental mechanism of the photoinduced reorientation of dye-doped liquid crystals. Applications of the same idea to other fields such as molecular biology and nanotechnology can however be envisioned. As an example, in this paper we work out a model of the actomyosin system based on the fluctuating-friction mechanism.Comment: to be published in J. Physics Condensed Matter (http://www.iop.org/Journals/JPhysCM

Assessment of Acute and Chronic Pharmacological Effects on Energy Expenditure and Macronutrient Oxidation in Humans: Responses to Ephedrine

Evidence of active brown adipose tissue in human adults suggests that this may become a pharmacological target to induce negative energy balance. We have explored whole-body indirect calorimetry to detect the metabolic effects of thermogenic drugs through administration of ephedrine hydrochloride and have assessed ephedrine's merits as a comparator compound in the evaluation of novel thermogenic agents. Volunteers randomly given ephedrine hydrochloride 15 mg QID (n = 8) or placebo (n = 6) were studied at baseline and after 1-2 and 14-15 days of treatment. We demonstrate that overnight or 23-hour, 2% energy expenditure (EE) and 5% fat (FO) or CHO oxidation effects are detectable both acutely and over 14 days. Compared to placebo, ephedrine increased EE and FO rates overnight (EE 63 kJ day 2, EE 105 kJ, FO 190 kJ, day 14), but not over 23 h. We conclude that modest energy expenditure and fat oxidation responses to pharmacological interventions can be confidently detected by calorimetry in small groups. Ephedrine should provide reliable data against which to compare novel thermogenic compounds

Factors associated with crisis pregnancies in Ireland: Findings from three nationally representative sexual health surveys

Background: Findings on the demographic and sexual health characteristics associated with the experience of a crisis pregnancy is important to inform the public health policy of a country, including Ireland. Findings from other jurisdictions have suggested that certain demographic groups are at risk for unintended pregnancies and the disparity between the groups have been growing in recent years. Ireland is a country which experienced much economic and societal change in the first decade of the 21st century, changes which are likely to have affected demographic variables pertaining to sexual health. The current study had two aims: to investigate changes in the socioeconomic characteristics associated with crisis pregnancies over a seven year period [2003 to 2010], and to investigate the recent [2010] socioeconomic risk factors associated with crisis pregnancies in Ireland. Methods: The study compared the results from 18-45 year old women using data from three broadly similar nationally representative Irish sexual health surveys carried out in 2003, 2004-2006 and 2010. Chi square analysis compared of the socioeconomic characteristics across the seven year period and found that a higher proportion of women with two or more children and women for whom religion was not important reported a crisis pregnancy in 2010 compared with earlier years. A logistic regression then investigated the sexual health history and socioeconomic factors associated with the experience of a recent crisis pregnancy using the most recent 2010 data. Results: Receipt of sex education and contraception use at first sex significantly predicted the experiencing of a recent crisis pregnancy. Younger women and those with a lower level of education were more likely to report having experienced a recent crisis pregnancy. Conclusion: Similar demographic groups are at risk for experiencing a crisis pregnancy in Ireland compared with international research, yet the disparities between demographic groups who have experienced a crisis pregnancy appear to be decreasing rather than increasing over a seven year period. Recommendations are made with regard to the provision of continued sex education throughout the lifespan, particularly for those women who are at an increased risk of experiencing a crisis pregnancy

Cooperative Transport of Brownian Particles

We consider the collective motion of finite-sized, overdamped Brownian particles (e.g., motor proteins) in a periodic potential. Simulations of our model have revealed a number of novel cooperative transport phenomena, including (i) the reversal of direction of the net current as the particle density is increased and (ii) a very strong and complex dependence of the average velocity on both the size and the average distance of the particles.Comment: 4 pages, 5 figure

Release of Carbon in Different Molecule Size Fractions from Decomposing Boreal Mor and Peat as Affected by Enchytraeid Worms

Terrestrial export of dissolved organic carbon (DOC) to watercourses has increased in boreal zone. Effect of decomposing material and soil food webs on the release rate and quality of DOC are poorly known. We quantified carbon (C) release in CO2, and DOC in different molecular weights from the most common organic soils in boreal zone; and explored the effect of soil type and enchytraeid worms on the release rates. Two types of mor and four types of peat were incubated in laboratory with and without enchytraeid worms for 154 days at + 15 A degrees C. Carbon was mostly released as CO2; DOC contributed to 2-9% of C release. The share of DOC was higher in peat than in mor. The release rate of CO2 was three times higher in mor than in highly decomposed peat. Enchytraeids enhanced the release of CO2 by 31-43% and of DOC by 46-77% in mor. High molecular weight fraction dominated the DOC release. Upscaling the laboratory results into catchment level allowed us to conclude that peatlands are the main source of DOC, low molecular weight DOC originates close to watercourse, and that enchytraeids substantially influence DOC leaching to watercourse and ultimately to aquatic CO2 emissions.Peer reviewe

Implementation and delivery of group consultations for young people with diabetes in socioeconomically deprived, ethnically diverse settings

BACKGROUND: Young people with diabetes experience poor clinical and psychosocial outcomes, and consider the health service ill-equipped in meeting their needs. Improvements, including alternative consulting approaches, are required to improve care quality and patient engagement. We examined how group-based, outpatient diabetes consultations might be delivered to support young people (16-25 years old) in socio-economically deprived, ethnically diverse settings. METHODS: This multi-method, comparative study recruited a total of 135 young people with diabetes across two implementation and two comparison sites (2017-2019). Informed by a 'researcher-in-residence' approach and complexity theory, we used a combination of methods: (a) 31 qualitative interviews with young people and staff and ethnographic observation in group and individual clinics, (b) quantitative analysis of sociodemographic, clinical, service use, and patient enablement data, and (c) micro-costing analysis. RESULTS: Implementation sites delivered 29 group consultations in total. Overall mean attendance per session was low, but a core group of young people attended repeatedly. They reported feeling better understood and supported, gaining new learning from peers and clinicians, and being better prepared to normalise diabetes self-care. Yet, there were also instances where peer comparison proved difficult to manage. Group consultations challenged deeply embedded ways of thinking about care provision and required staff to work flexibly to achieve local tailoring, sustain continuity, and safely manage complex interdependencies with other care processes. Set-up and delivery were time-consuming and required in-depth clinical and relational knowledge of patients. Facilitation by an experienced youth worker was instrumental. There was indication that economic value could derive from preventing at least one unscheduled consultation annually. CONCLUSIONS: Group consulting can provide added value when tailored to meet local needs rather than following standardised approaches. This study illustrates the importance of adaptive capability and self-organisation when integrating new models of care, with young people as active partners in shaping service provision. TRIAL REGISTRATION: ISRCTN reference 27989430

Bronchopulmonary Dysplasia: Executive Summary of a Workshop

Comment in Bronchopulmonary Dysplasia: The Ongoing Search for One Definition to Rule Them All. [J Pediatr. 2018] Midlife crisis? In its 50th year, BPD redefines itself. [J Pediatr. 2018