Nonlinear network model analysis of vibrational energy transfer and localisation in the Fenna-Matthews-Olson complex

Collective protein modes are expected to be important for facilitating energy transfer in the Fenna-Matthews-Olson (FMO) complex of photosynthetic green sulphur bacteria, however to date little work has focussed on the microscopic details of these vibrations. The nonlinear network model (NNM) provides a computationally inexpensive approach to studying vibrational modes at the microscopic level in large protein structures, whilst incorporating anharmonicity in the inter-residue interactions which can influence protein dynamics. We apply the NNM to the entire trimeric FMO complex and find evidence for the existence of nonlinear discrete breather modes. These modes tend to transfer energy to the highly connected core pigments, potentially opening up alternative excitation energy transfer routes through their influence on pigment properties. Incorporating localised modes based on these discrete breathers in the optical spectra calculations for FMO using ab initio site energies and excitonic couplings can substantially improve their agreement with experimental results.A.W.C. and S.E.M. acknowledge support from the Winton Programme for the Physics of Sustainability. S.E.M. is also supported by an EPSRC doctoral training award. D.J.C. is supported by a Marie Curie International Outgoing Fellowship within the seventh European Community Framework Programme

Curry-assisted diagnosis in the rheumatology clinic.

We report five cases of glucocorticoid-responsive mouth symptoms in polymyalgia rheumatica/giant cell arteritis (GCA); three cases of tongue pain exacerbated by hot/spicy food, a case of scalp pain made worse by eating hot/spicy food and a case of sore tongue as a presenting feature of GCA. These cases emphasize the importance of asking about mouth symptoms and changes in taste when evaluating patients with suspected GCA

Detection of anti-drug antibodies using a bridging ELISA compared with radioimmunoassay in adalimumab-treated rheumatoid arthritis patients with random drug levels

Objective: To determine the concordance between RIA and bridging ELISA at detecting anti-drug antibodies (ADAbs) in the context of random adalimumab levels and investigate the additional clinical utility of detecting ADAbs in RA patients who test ADAb positive by RIA and negative by ELISA. Methods: ADAb levels were determined using RIA and bridging ELISA in 63 adalimumab treated RA patients (159 samples). Immunogenicity concordance was determined using receiver-operating characteristic (ROC) curves. To determine the additional clinical value provided by a positive RIA in the presence of negative ELISA, association between treatment response (ΔDAS28), adalimumab drug levels and ADAbs was evaluated longitudinally using generalised estimating equation. Results: Of the 60 RIA+ samples (n=31 patients), 19 (n=10 patients) were also ELISA+, corresponding to 31.7% of samples. Area under the curve (AUC) for detecting ADAbs using ELISA (compared with RIA) using ROC curves was 0.65 (95% CI: 0.59-0.71); this increased to 0.91 (95% CI: 0.81-0.99) if ADAbs were ≥100 AU/ml using RIA. In RIA+/ELISA- patients, adalimumab levels were associated with ΔDAS28 over 12 months [regression coefficient: 0.098 (0.043-0.15), p<0.0001] and whilst ADAbs were significantly associated with drug level, they were not directly associated with ΔDAS28 over 12 months [β coefficient: 0.00083 (-0.0038 to 0.0054), p=0.72]. Conclusion: ADAbs were detected using ELISA more frequently when present in high titres as measured by RIA. In RIA+/ELISA- patients, only drug levels were significantly associated with treatment response. Although ADAbs were not independently associated with treatment response, they may be helpful in determining the aetiology of low drug levels

Differential Methylation as a Biomarker of Response to Etanercept in Patients With Rheumatoid Arthritis

Objective: Biologic drug therapies represent a huge advance in the treatment of rheumatoid arthritis (RA). However, very good disease control is achieved in only 30% of patients, making identification of biomarkers of response a research priority. We undertook this study to test our hypothesis that differential DNA methylation patterns may provide biomarkers predictive of response to tumor necrosis factor inhibitor (TNFi) therapy in patients with RA. Methods: An epigenome-wide association study was performed on pretreatment whole blood DNA from patients with RA. Patients who displayed good response (n = 36) or no response (n = 36) to etanercept therapy at 3 months were selected. Differentially methylated positions were identified using linear regression. Variance of methylation at differentially methylated positions was assessed for correlation with cis-acting single-nucleotide polymorphisms (SNPs). A replication experiment for prioritized SNPs was performed in an independent cohort of 1,204 RA patients. Results: Five positions that were differentially methylated between responder groups were identified, with a false discovery rate of <5%. The top 2 differentially methylated positions mapped to exon 7 of the LRPAP1 gene on chromosome 4 (cg04857395, P = 1.39 × 10−8 and cg26401028, P = 1.69 × 10−8). The A allele of the SNP rs3468 was correlated with higher levels of methylation for both of the top 2 differentially methylated positions (P = 2.63 × 10−7 and P = 1.05 × 10−6, respectively). Furthermore, the A allele of rs3468 was correlated with European League Against Rheumatism nonresponse in the discovery cohort (P = 0.03; n = 56) and in the independent replication cohort (P = 0.003; n = 1,204). Conclusion: We identify DNA methylation as a potential biomarker of response to TNFi therapy, and we report the association between response and the LRPAP1 gene, which encodes a chaperone of low-density lipoprotein receptor–related protein 1. Additional replication experiments in independent sample collections are now needed

Методи оцінки ризиків в інформаційній системі аналізу екологічного стану басейну малої ріки

В інформаційній системі аналізу стану басейну малої ріки запропоновано методи оцінки ризиків на основі імовірнісних та статистичних оцінок, формалізації моделі гри з природою, прогнозування процесів підтоплення земель з використанням ланцюгів Маркова, розглянуто багато критеріальні моделі ризиків.In informational and analytical system of the small rivers’ ecological condition estimation the methods of risks modelling on the basis of likelihood and statistical estimations, formalization of models of game with nature, risk modelling and forecasting processes flooded lands using Markov chains are offered, multicriteria models of risks are considered

Non-state nations: Structure, rescaling, and the role of territorial policy communities, illustrated by the cases of Wales and Sardinia

This paper explores the role of non-state nations’ identity and agency with regard to relations with their host nation states. The particular focus here is on the means by which such regions might express their individuality. To this end, we employ a comparative case study analysis of two non-state nations with a range of differing yet in other ways similar qualities – namely Wales (UK) and Sardinia (Italy). We suggest that this is a valuable exercise, allowing as it does for the exploring of evidence ‘on the ground’ of the processes involved. The conceptual rationale for the paper is provided by new regionalism – regions as actors beyond the nation state. Following this, the idea of the ‘territorial policy community’ is presented as a point of departure, with the scope of the paper being to develop a diachronic framework for regional change. Given the focus on identity and interest articulation, the role of regional political parties is a particular subject of the empirical investigation, with non-state nations and nation states linked by opportunistic relationships based on political and electoral support. We then consider what this might mean with regard to the capacity of non-state nations to build on the past to successfully negotiate future policy-making agendas. Finally, we reflect on the limitations of the study, and consider the implications of its findings for further research agendas

Evaluating the feasibility of a web-based weight loss programme for naval service personnel with excess body weight.

Overweight and obesity are a major concern that may influence the operational capacity of the UK Naval Service (NS). This study was conducted to evaluate the feasibility of trialling and implementing a modified web-based weight loss programme for overweight and obese NS personnel.Royal Navy; University of Southampto

Photoperiod Regulates Lean Mass Accretion, but Not Adiposity, in Growing F344 Rats Fed a High Fat Diet

yesIn this study the effects of photoperiod and diet, and their interaction, were examined for their effects on growth and body composition in juvenile F344 rats over a 4-week period. On long (16L:8D), relative to short (8L:16D), photoperiod food intake and growth rate were increased, but percentage adiposity remained constant (ca 3-4%). On a high fat diet (HFD), containing 22.8% fat (45% energy as fat), food intake was reduced, but energy intake increased on both photoperiods. This led to a small increase in adiposity (up to 10%) without overt change in body weight. These changes were also reflected in plasma leptin and lipid levels. Importantly while both lean and adipose tissue were strongly regulated by photoperiod on a chow diet, this regulation was lost for adipose, but not lean tissue, on HFD. This implies that a primary effect of photoperiod is the regulation of growth and lean mass accretion. Consistent with this both hypothalamic GHRH gene expression and serum IGF-1 levels were photoperiod dependent. As for other animals and humans, there was evidence of central hyposomatotropism in response to obesity, as GHRH gene expression was suppressed by the HFD. Gene expression of hypothalamic AgRP and CRH, but not NPY nor POMC, accorded with the energy balance status on long and short photoperiod. However, there was a general dissociation between plasma leptin levels and expression of these hypothalamic energy balance genes. Similarly there was no interaction between the HFD and photoperiod at the level of the genes involved in thyroid hormone metabolism (Dio2, Dio3, TSHβ or NMU), which are important mediators of the photoperiodic response. These data suggest that photoperiod and HFD influence body weight and body composition through independent mechanisms but in each case the role of the hypothalamic energy balance genes is not predictable based on their known function.Scottish Government (Rural and Environment Science and Analytical Services Division, http://www.scotland.gov.uk/), AWR LR LMT PJM and the BBSRC, (http://www.bbsrc.ac.uk/home/home.aspx, grant BB/K001043/1), AWR GH PJ

Psychological determinants of whole-body endurance performance

Background: No literature reviews have systematically identified and evaluated research on the psychological determinants of endurance performance, and sport psychology performance-enhancement guidelines for endurance sports are not founded on a systematic appraisal of endurance-specific research. Objective: A systematic literature review was conducted to identify practical psychological interventions that improve endurance performance and to identify additional psychological factors that affect endurance performance. Additional objectives were to evaluate the research practices of included studies, to suggest theoretical and applied implications, and to guide future research. Methods: Electronic databases, forward-citation searches, and manual searches of reference lists were used to locate relevant studies. Peer-reviewed studies were included when they chose an experimental or quasi-experimental research design, a psychological manipulation, endurance performance as the dependent variable, and athletes or physically-active, healthy adults as participants. Results: Consistent support was found for using imagery, self-talk, and goal setting to improve endurance performance, but it is unclear whether learning multiple psychological skills is more beneficial than learning one psychological skill. The results also demonstrated that mental fatigue undermines endurance performance, and verbal encouragement and head-to-head competition can have a beneficial effect. Interventions that influenced perception of effort consistently affected endurance performance. Conclusions: Psychological skills training could benefit an endurance athlete. Researchers are encouraged to compare different practical psychological interventions, to examine the effects of these interventions for athletes in competition, and to include a placebo control condition or an alternative control treatment. Researchers are also encouraged to explore additional psychological factors that could have a negative effect on endurance performance. Future research should include psychological mediating variables and moderating variables. Implications for theoretical explanations of endurance performance and evidence-based practice are described

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201