Although it is widely accepted that cancer-derived extracellular vesicles (EVs) carry DNA cargo, the association of cell-free circulating DNA (cfDNA) and EVs in plasma of healthy humans remains elusive. Using a physiological exercise model, where EVs and cfDNA are synchronously released, we aimed to characterize the kinetics and localization of DNA associated with EVs. EVs were separated from human plasma using size exclusion chromatography or immuno-affinity capture for CD9+, CD63+, and CD81+ EVs. DNA was quantified with an ultra-sensitive qPCR assay targeting repetitive LINE elements, with or without DNase digestion. This model shows that a minute part of circulating cell-free DNA is associated with EVs. During rest and following exercise, only 0.12% of the total cfDNA occurs in association with CD9+/CD63+/CD81+EVs. DNase digestion experiments indicate that the largest part of EV associated DNA is sensitive to DNase digestion and only ~20% are protected within the lumen of the separated EVs. A single bout of running or cycling exercise increases the levels of EVs, cfDNA, and EV-associated DNA. While EV surface DNA is increasing, DNAse-resistant DNA remains at resting levels, indicating that EVs released during exercise (ExerVs) do not contain DNA. Consequently, DNA is largely associated with the outer surface of circulating EVs. ExerVs recruit cfDNA to their corona, but do not carry DNA in their lumen.
Abstract--Experimentswere carried out on the isolated papillary muscle of the rabbit in order to further characterize the n-adrenoceptors mediating the positive inotropic effect. For this purpose dose-response relations of seven sympathomimetic amines were compared under the influence of a and!or N-adrenolytic drugs. Phentolamine (10-s M) shifted the lower part of the dose-response curves for norfenephrine, syn ephrine and epinine as for phenylephrine and adrenaline to the right, while prindolol (10-s M) affected only the upper part of the curves. In the presence of both a and adrenoceptor blocking agents the entire dose-response curves for sympathomimetic amines were shifted in a parallel manner. Noradrenaline affected preferentiallyThe question of whether or not the positive inotropic response to sympathomimetic amines is mediated via a-adrenoceptors in the atrial myocardium is still under discussion:since Govier (1, 2) has reported that in the left atrium of the guinea-pig a-adrenoceptors are responsible for inducing partly the positive inotropic effect of phenylephrine, adrenaline and noradrenaline, papers supporting as well as contradicting his observations have been pre sented. (n experiments on the left atrium of the rabbit (3-6) as well as of the rat (7) these observations of Govier were confirmed. On the spontaneously beating rabbit atrium, how ever, the positive inotropic effect of phenylephrine was due to stimulation of ~ but not of a-adrenoceptors (8).Consistent with the latter observations, recent experiments in our laboratory demon strated that only 3 not a-adrenoceptors mediated the positive inotropic as well as ehrono ' This work was supported by the Deutsche Forschungsgemeinschaft Present address:
Background Regular participation in exercise is important for people with cystic fibrosis (CF). Therefore, we implemented a personalized, web-based exercise intervention over the course of one year for people with CF. The aims were to investigate the feasibility of the intervention and to evaluate changes in exercise participation, lung function, and exercise capacity. Methods In total, 11/17 participants [aged 12–52 years; FEV1%pred. 72.3 (SD: 17.3)] were included in the final data analysis. Every week, the participants received an individual training recommendation at the start and uploaded their training report on our website at the end of each week. The number of training minutes and sessions performed were analyzed over 13 four-week training sections. The participation in exercise (physical activity questionnaire), lung function and exercise capacity were assessed at baseline (T0), after 12 weeks (T1) and after 52 weeks (T2). Results A training duration of 178 min (SD: 75.5) and 3.3 (SD: 0.89) training sessions could be achieved weekly. In the first four-week training section, the participants performed 137.31 (SD: 95.7) minutes of training, with an increase of 42% in the third training section (195.01, SD: 134.99). Minutes of training reported on the questionnaire increased by 39.7% from T0 (179.38 min, SD: 120.9) to T1 (250.63 min, SD: 124.1) but decreased at T2 (166.88, SD: 155.4). There were slight decreases in lung function (FEV1 − 3.9%pred.; FVC − 1.9%pred.) and slight increases in exercise capacity (VO2peak + 1.5 ml/min/kg; six-minute-walk-test-distance + 26 m). Noticeably, five participants experienced deteriorations in their FEV1 of more than 5% but simultaneously experienced improvements in the parameters of exercise capacity of more than 5% throughout the year. Conclusions The web-based concept was feasible for the participants over the course of a year and supported exercise participation. The improvement in exercise capacity due to increased exercise participation over a prolonged period of time, despite a decrease in lung function, should be further investigated. Finally, if integrated into usual care, this approach could facilitate the prescription of regular personalized exercise and promote exercise participation in the daily lives of people with CF.
End-to-end broadband service delivery requires remote management of devices in the home network, beyond the home gateway (HG). The service provider can only put limited requirements to these of-the-shelf devices, and therefore has to make intelligent use of their given control and management protocols. The authors propose architectures for the unique remote discovery and management of such devices in a highly heterogeneous home network. We suggest to have the HG discovering these devices and to proxy management and control actions to the provider's remote servers. This approach has been recently adopted by the Home Gateway Initiative. A proof-ofconcept is described for the remote management of UPnP devices in the home with a simple TR-069/UPnP proxy on the HG, but the architecture is basically generic for any combination of webservices like protocols.
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