498 research outputs found

    Synthetically tuneable biomimetic artificial photosynthetic reaction centres that closely resemble the natural system in purple bacteria

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    © 2016 The Royal Society of Chemistry. Porphyrin-based photosynthetic reaction centre (PRC) mimics, ZnPQ-Q2HP-C60 and MP2Q-Q2HP-C60 (M = Zn or 2H), designed to have a similar special-pair electron donor and similar charge-separation distances, redox processes and photochemical reaction rates to those in the natural PRC from purple bacteria, have been synthesised and extensive photochemical studies performed. Mechanisms of electron-transfer reactions are fully investigated using femtosecond and nanosecond transient absorption spectroscopy. In benzonitrile, all models show picosecond-timescale charge-separations and the final singlet charge-separations with the microsecond-timescale. The established lifetimes are long compared to other processes in organic solar cells or other organic light harvesting systems. These rigid, synthetically flexible molecules provide the closest mimics to the natural PRC so far synthesised and present a future direction for the design of light harvesters with controllable absorption, redox, and kinetics properties

    Dynamic coupling of fast channel gating with slow ATP-turnover underpins protein transport through the Sec translocon.

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    The Sec translocon is a highly conserved membrane assembly for polypeptide transport across, or into, lipid bilayers. In bacteria, secretion through the core channel complex-SecYEG in the inner membrane-is powered by the cytosolic ATPase SecA. Here, we use single-molecule fluorescence to interrogate the conformational state of SecYEG throughout the ATP hydrolysis cycle of SecA. We show that the SecYEG channel fluctuations between open and closed states are much faster (~20-fold during translocation) than ATP turnover, and that the nucleotide status of SecA modulates the rates of opening and closure. The SecY variant PrlA4, which exhibits faster transport but unaffected ATPase rates, increases the dwell time in the open state, facilitating pre-protein diffusion through the pore and thereby enhancing translocation efficiency. Thus, rapid SecYEG channel dynamics are allosterically coupled to SecA via modulation of the energy landscape, and play an integral part in protein transport. Loose coupling of ATP-turnover by SecA to the dynamic properties of SecYEG is compatible with a Brownian-rachet mechanism of translocation, rather than strict nucleotide-dependent interconversion between different static states of a power stroke

    Early intervention for adolescents with Patellofemoral Pain Syndrome - a pragmatic cluster randomised controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Self-reported knee pain is highly prevalent among adolescents. As much as 50% of the non-specific knee pain may be attributed to Patellofemoral Pain Syndrome (PFPS). In the short term, exercise therapy appears to have a better effect than patient education consisting of written information and general advice on exercise or compared with placebo treatment. But the long-term effect of exercise therapy compared with patient education is conflicting. The purpose of this study is to examine the short- and long-term effectiveness of patient education compared with patient education and multimodal physiotherapy applied at a very early stage of the condition among adolescents.</p> <p>Methods/Design</p> <p>This study is a single blind pragmatic cluster randomised controlled trial. Four upper secondary schools have been invited to participate in the study (approximately 2500 students, aged 15-19 years). Students are asked to answer an online questionnaire regarding musculoskeletal pain. The students who report knee pain are contacted by telephone and offered a clinical examination by a rheumatologist. Subjects who fit the inclusion criteria and are diagnosed with PFPS are invited to participate in the study. A minimum of 102 students with PFPS are then cluster-randomised into two intervention groups based on which school they attend. Both intervention groups receive written information and education. In addition to patient education, one group receives multimodal physiotherapy consisting primarily of neuromuscular training of the muscles around the foot, knee and hip and home exercises.</p> <p>The students with PFPS fill out self-reported questionnaires at baseline, 3, 6, 12 and 24 months after inclusion in the study. The primary outcome measure is perception of recovery measured on a 7-point Likert scale ranging from "completely recovered" to "worse than ever" at 12 months.</p> <p>Discussion</p> <p>This study is designed to investigate the effectiveness of patient education compared with patient education combined with multimodal physiotherapy. If patient education and multimodal physiotherapy applied at an early stage of Patellofemoral Pain Syndrome proves effective, it may serve as a basis for optimising the clinical pathway for those suffering from the condition, where specific emphasis can be placed on early diagnosis and early treatment.</p> <p>Trial Registration</p> <p>clinicaltrials.gov reference: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01438762">NCT01438762</a></p

    Extracellular Matrix Aggregates from Differentiating Embryoid Bodies as a Scaffold to Support ESC Proliferation and Differentiation

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    Embryonic stem cells (ESCs) have emerged as potential cell sources for tissue engineering and regeneration owing to its virtually unlimited replicative capacity and the potential to differentiate into a variety of cell types. Current differentiation strategies primarily involve various growth factor/inducer/repressor concoctions with less emphasis on the substrate. Developing biomaterials to promote stem cell proliferation and differentiation could aid in the realization of this goal. Extracellular matrix (ECM) components are important physiological regulators, and can provide cues to direct ESC expansion and differentiation. ECM undergoes constant remodeling with surrounding cells to accommodate specific developmental event. In this study, using ESC derived aggregates called embryoid bodies (EB) as a model, we characterized the biological nature of ECM in EB after exposure to different treatments: spontaneously differentiated and retinoic acid treated (denoted as SPT and RA, respectively). Next, we extracted this treatment-specific ECM by detergent decellularization methods (Triton X-100, DOC and SDS are compared). The resulting EB ECM scaffolds were seeded with undifferentiated ESCs using a novel cell seeding strategy, and the behavior of ESCs was studied. Our results showed that the optimized protocol efficiently removes cells while retaining crucial ECM and biochemical components. Decellularized ECM from SPT EB gave rise to a more favorable microenvironment for promoting ESC attachment, proliferation, and early differentiation, compared to native EB and decellularized ECM from RA EB. These findings suggest that various treatment conditions allow the formulation of unique ESC-ECM derived scaffolds to enhance ESC bioactivities, including proliferation and differentiation for tissue regeneration applications. © 2013 Goh et al

    The writing on the wall: the concealed communities of the East Yorkshire horselads

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    This paper examines the graffiti found within late nineteenth and early-twentieth century farm buildings in the Wolds of East Yorkshire. It suggests that the graffiti were created by a group of young men at the bottom of the social hierarchy - the horselads – and was one of the ways in which they constructed a distinctive sense of communal identity, at a particular stage in their lives. Whilst it tells us much about changing agricultural regimes and social structures, it also informs us about experiences and attitudes often hidden from official histories and biographies. In this way, the graffiti are argued to inform our understanding, not only of a concealed community, but also about their hidden histor

    Knee arthroscopy and exercise versus exercise only for chronic patellofemoral pain syndrome: a randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Arthroscopy is often used to treat patients with chronic patellofemoral pain syndrome (PFPS). As there is a lack of evidence, we conducted a randomized controlled trial to study the efficacy of arthroscopy in patients with chronic PFPS.</p> <p>Methods</p> <p>A total of 56 patients with chronic PFPS were randomized into two treatment groups: an <it>arthroscopy group </it>(<it>N </it>= 28), treated with knee arthroscopy and an 8-week home exercise program, and a <it>control group </it>(<it>N </it>= 28), treated with the 8-week home exercise program only. The arthroscopy included finding-specific surgical procedures according to current recommendations. The primary outcome was the Kujala score on patellofemoral pain and function at 9 months following randomization. Secondary outcomes were visual analog scales (VASs) to assess activity-related symptoms. We also estimated the direct healthcare costs.</p> <p>Results</p> <p>Both groups showed marked improvement during the follow-up. The mean improvement in the Kujala score was 12.9 (95% confidence interval (CI) 8.2–17.6) in the arthroscopy group and 11.4 (95% CI 6.9–15.8) in the control group. However, there was no difference between the groups in mean improvement in the Kujala score (group difference 1.1 (95% CI -7.4 - 5.2)) or in any of the VAS scores. Total direct healthcare costs in the arthroscopy group were estimated to exceed on average those of the control group by €901 per patient (<it>p </it>< 0.001).</p> <p>Conclusion</p> <p>In this controlled trial involving patients with chronic PFPS, the outcome when arthroscopy was used in addition to a home exercise program was no better than when the home exercise program was used alone.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN 41800323</p

    “Did I bring it on myself?” An exploratory study of the beliefs that adolescents referred to mental health services have about the causes of their depression

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    Background: The causal beliefs which adults have regarding their mental health difficulties have been linked to help-seeking behaviour, treatment preferences and the outcome of therapy; yet the topic remains a relatively unexplored one in the adolescent literature. Aims: This exploratory study aims to explore the causal beliefs regarding depression among a sample of clinically referred adolescents. Design: 77 adolescents, aged between 11 and 17, all diagnosed with moderate to severe depression, were interviewed using a semi-structured interview schedule, at the beginning of their participation in a randomised controlled trial. Data were analysed qualitatively using Framework Analysis. Findings: The study identified three themes related to causal beliefs: 1) Bewilderment about why they were depressed; 2) Depression as a result of rejection, victimisation and stress; and 3) Something inside is to blame. Conclusion: Although some adolescents struggled to identify the causes of their depression, many identified stressful life experiences as the cause of their current depression. They also tended to emphasise their own negative ways of interpreting those events, and some believed that their depression was caused by something inside them. Adolescents’ causal beliefs are likely to have implications for the way they seek help and engage in treatment, making it important to understand how adolescents understand their difficulties

    Patellofemoral pain syndrome (PFPS): a systematic review of anatomy and potential risk factors

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    Patellofemoral Pain Syndrome (PFPS), a common cause of anterior knee pain, is successfully treated in over 2/3 of patients through rehabilitation protocols designed to reduce pain and return function to the individual. Applying preventive medicine strategies, the majority of cases of PFPS may be avoided if a pre-diagnosis can be made by clinician or certified athletic trainer testing the current researched potential risk factors during a Preparticipation Screening Evaluation (PPSE). We provide a detailed and comprehensive review of the soft tissue, arterial system, and innervation to the patellofemoral joint in order to supply the clinician with the knowledge required to assess the anatomy and make recommendations to patients identified as potentially at risk. The purpose of this article is to review knee anatomy and the literature regarding potential risk factors associated with patellofemoral pain syndrome and prehabilitation strategies. A comprehensive review of knee anatomy will present the relationships of arterial collateralization, innervations, and soft tissue alignment to the possible multifactoral mechanism involved in PFPS, while attempting to advocate future use of different treatments aimed at non-soft tissue causes of PFPS
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