Energy landscape mapping and replica exchange molecular dynamics of an adsorbed peptide

Adsorption of peptides at the interface between a fluid and a solid occurs widely in both nature and applications. Knowing the dominant conformations of adsorbed peptides and the energy barriers between them is of interest for a variety of reasons. Molecular dynamics (MD) simulation is a widely used technique that can yield such understanding. However, the complexity of the energy landscapes of adsorbed peptides means that comprehensive exploration of the energy landscape by MD simulation is challenging. An alternative approach is energy landscape mapping (ELM), which involves the location of stationary points on the potential energy surface, and its analysis to determine, for example, the pathways and energy barriers between them. In the study reported here, a comparison is made between this technique and replica exchange molecular dynamics (REMD) for met-enkephalin adsorbed at the interface between graphite and the gas phase: the first ever direct comparison of these techniques for adsorbed peptides. Both methods yield the dominant adsorbed peptide conformations. Unlike REMD, however, ELM readily allows the identification of the connectivity and energy barriers between the favored conformations, transition paths, and structures between these conformations and the impact of entropy. It also permits the calculation of the constant volume heat capacity although the accuracy of this is limited by the sampling of high-energy minima. Overall, compared to REMD, ELM provides additional insights into the adsorbed peptide system provided sufficient care is taken to ensure that key parts of the landscape are adequately sampled

Energy landscapes of a pair of adsorbed peptides

The wide relevance of peptide adsorption in natural and synthetic contexts means it has attracted much attention. Molecular dynamics (MD) simulation has been widely used in these endeavors. Much of this has focused on single peptides due to the computational effort required to capture the rare events that characterize their adsorption. This focus is, however, of limited practical relevance as in reality, most systems of interest operate in the nondilute regime where peptides will interact with other adsorbed peptides. As an alternative to MD simulation, we have used energy landscape mapping (ELM) to investigate two met-enkephalin molecules adsorbed at a gas/graphite interface. Major conformations of the adsorbed peptides and the connecting transition states are elucidated along with the associated energy barriers and rates of exchange. The last of these makes clear that MD simulations are currently of limited use in probing the co-adsorption of two peptides, let alone more. The constant volume heat capacity as a function of temperature is also presented. Overall, this study represents a significant step toward characterizing peptide adsorption beyond the dilute limit

Using interpretative phenomenological analysis to inform physiotherapy practice: An introduction with reference to the lived experience of cerebellar ataxia

The attached file is a pre-published version of the full and final paper which can be found at the link below.This article has been made available through the Brunel Open Access Publishing Fund.Qualitative research methods that focus on the lived experience of people with health conditions are relatively underutilised in physiotherapy research. This article aims to introduce interpretative phenomenological analysis (IPA), a research methodology oriented toward exploring and understanding the experience of a particular phenomenon (e.g., living with spinal cord injury or chronic pain, or being the carer of someone with a particular health condition). Researchers using IPA try to find out how people make sense of their experiences and the meanings they attach to them. The findings from IPA research are highly nuanced and offer a fine grained understanding that can be used to contextualise existing quantitative research, to inform understanding of novel or underresearched topics or, in their own right, to provoke a reappraisal of what is considered known about a specified phenomenon. We advocate IPA as a useful and accessible approach to qualitative research that can be used in the clinical setting to inform physiotherapy practice and the development of services from the perspective of individuals with particular health conditions.This article is available through the Brunel Open Access Publishing Fund

When benefit eligibility and patient-led care intersect. Living in the UK with chronic illness:Experiences of the work capability assessment

Individuals living with chronic physical health conditions are more likely to be out-of-work than other groups. Often framed as a 'response' to these statistics, many countries have introduced policy instruments for promoting the employment of individuals with chronic conditions. This qualitative study sought to explore the impact of welfare reforms on UK individuals. Employing a phenomenological approach, semi-structured interviews were conducted with five participants living with chronic conditions. Three themes were generated using Interpretative Phenomenological Analysis: 'intersubjective sense making of the condition'; 'battles for control' and 'the fluidity and strengthening of identity'. Implications for further, holistic, policy reform are explored

Physically active academic lessons; Acceptance, barriers and facilitators for implementation

Background To improve health and academic learning in schoolchildren, the Active School programme in Stavanger, Norway has introduced physically active academic lessons. This is a teaching method combining physical activity with academic content. The purpose of this paper was to evaluate the response to the physically active lessons and identify facilitators and barriers for implementation of such an intervention. Methods Five school leaders (principals or vice-principals), 13 teachers and 30 children from the five intervention schools were interviewed about their experiences with the 10-month intervention, which consisted of weekly minimum 2 × 45 minutes of physically active academic lessons, and the factors affecting its implementation. All interviews were transcribed and analysed using the qualitative data analysis program NVivo 10 (QSR international, London, UK). In addition, weekly teacher’s intervention delivery logs were collected and analysed. Results On average, the physically active academic lessons in 18 of the 34 weeks (53%) were reported in the teacher logs. The number of delivered physically active academic lessons covered 73% of the schools’ planned activity. Physically active lessons were well received among school leaders, teachers and children. The main facilitators for implementation of the physically active lessons were active leadership and teacher support, high self-efficacy regarding mastering the intervention, ease of organizing physically active lessons, inclusion of physically active lessons into the lesson curricula, and children’s positive reception of the intervention. The main barriers were unclear expectations, lack of knowledge and time to plan the physiclly active lessons, and the length of the physically active lessons (15–20 min lessons were preferred over the 45 min lessons). Conclusion Physically active academic lessons were considered an appropriate pedagogical method for creating positive variation, and were highly appreciated among both teachers and children. Both the principal and the teachers should be actively involved the implementation, which could be strengthened by including physical activity into the school’s strategy. Barriers for implementing physically active lessons in schools could be lowered by increasing implementation clarity and introducing the teachers to high quality and easily organized lessons.publishedVersio

Are There Age Spreads in Star Forming Regions?

A luminosity spread at a given effective temperature is ubiquitously seen in the Hertzsprung-Russell (HR) diagrams of young star forming regions and often interpreted in terms of a prolonged period (>=10 Myr) of star formation. I review the evidence that the observed luminosity spreads are genuine and not caused by astrophysical sources of scatter. I then address whether the luminosity spreads necessarily imply large age spreads, by comparing HR diagram ages with ages from independent clocks such as stellar rotation rate, the presence of circumstellar material and lithium depletion. I argue that whilst there probably is a true luminosity dispersion, there is little evidence to support age spreads larger than a few Myr. This paradox could be resolved by brief periods of rapid accretion during the class I pre main-sequence phase.Comment: To appear in the proceedings of JENAM10: Star Clusters in the Era of Large Surveys, 8 page

Genetic analysis of haemophilia A in Bulgaria

BACKGROUND: Haemophilias are the most common hereditary severe disorders of blood clotting. In families afflicted with heamophilia, genetic analysis provides opportunities to prevent recurrence of the disease. This study establishes a diagnostical strategy for carriership determination and prenatal diagnostics of haemophilia A in Bulgarian haemophilic population. METHODS: A diagnostical strategy consisting of screening for most common mutations in the factor VIII gene and analysis of a panel of eight linked to the factor VIII gene locus polymorphisms was established. RESULTS: Polymorphic analysis for carrier status determination of haemophilia A was successful in 30 families out of 32 (94%). Carrier status was determined in 25 of a total of 28 women at risk (89%). Fourteen prenatal diagnoses in women at high risk of having a haemophilia A – affected child were performed, resulting in 6 healthy boys and 5 girls. CONCLUSION: The compound approach proves to be a highly informative and cost-effective strategy for prevention of recurrence of haemophilia A in Bulgaria. DNA analysis facilitates carriership determination and subsequent prenatal diagnosis in the majority of Bulgarian families affected by haemophilia A

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia.

Introduction: The change in bone turnover markers (BTM) in response to osteoporosis therapy can be assessed by a decrease beyond the least significant change (LSC) or below the mean of the reference interval (RI). We compared the performance of these two approaches in women treated with raloxifene. Methods: Fifty postmenopausal osteopenic women, (age 51-72y) were randomised to raloxifene or no treatment for 2 years. Blood samples were collected for the measurement of BTM. The LSC for each marker was calculated from the untreated women and the RI obtained from healthy premenopausal women (age 35-40y). Bone mineral density (BMD) was measured at the spine and hip. Results: There was a decrease in BTM in response to raloxifene treatment; percentage change at 12 weeks, CTX -39% (95% CI -48 to -28) and PINP -32% (95% CI -40 to -23) P<0.001. The proportion of women classified as responding to treatment using LSC at 12 weeks was: CTX 38%, PINP 52%, at 48 weeks CTX 60%, PINP 65%. For the RI approach; at 12 weeks CTX and PINP 38%, at 48 weeks CTX 40%, PINP 45%. There was a significant difference in the change in spine BMD in the raloxifene treated group compared to the no-treatment group at week 48; difference 0.031 g/cm2, (95% CI 0.016 to 0.046, P<0.001). Conclusions: The two approaches identified women that reached the target for treatment using BTM. Both LSC and RI criteria appear useful in identifying treatment response but the two approaches do not fully overlap and may be complementary

Edible crabs “Go West”: migrations and incubation cycle of Cancer pagurus revealed by electronic tags

Crustaceans are key components of marine ecosystems which, like other exploited marine taxa, show seasonable patterns of distribution and activity, with consequences for their availability to capture by targeted fisheries. Despite concerns over the sustainability of crab fisheries worldwide, difficulties in observing crabs’ behaviour over their annual cycles, and the timings and durations of reproduction, remain poorly understood. From the release of 128 mature female edible crabs tagged with electronic data storage tags (DSTs), we demonstrate predominantly westward migration in the English Channel. Eastern Channel crabs migrated further than western Channel crabs, while crabs released outside the Channel showed little or no migration. Individual migrations were punctuated by a 7-month hiatus, when crabs remained stationary, coincident with the main period of crab spawning and egg incubation. Incubation commenced earlier in the west, from late October onwards, and brooding locations, determined using tidal geolocation, occurred throughout the species range. With an overall return rate of 34%, our results demonstrate that previous reluctance to tag crabs with relatively high-cost DSTs for fear of loss following moulting is unfounded, and that DSTs can generate precise information with regards life-history metrics that would be unachievable using other conventional means

A primary cutaneous adenoid-cystic carcinoma in a young woman. Differential diagnosis and clinical implications

Primary cutaneous adenoid-cystic carcinoma (PCACC) is a rare slow-growing neoplasm of disputed histogenesis characterized by a cribriform pattern at histology and local aggressive behaviour. Up to date about 60 cases of PCACC have been reported in the literature. This tumour is most common in the scalp, affects middle-aged and older individuals (mean age 59) and has predilection for women. We describe an unexpected case of PCACC in a 32-years-old woman referred to our clinic for a subcutaneous nodule in the scalp showing a slow growth and indolent course. The differential diagnosis and the clinical management of this PCACC patient, successfully treated with a wide local excision, are presented and discussed