• Enemark Jordan posted an update 6 days, 12 hours ago

    Thus, the transition of myelin ultrastructure from correlated to uncorrelated disordered state, is principally affected by the deformation of the membrane and extracellular domain. Daptomycin is a lipopeptide antibiotic that is important in the treatment of infections with Gram-positive bacteria. In the presence of calcium, daptomycin binds to phosphatidylglycerol in the bacterial cytoplasmic membrane and then forms oligomers that mediate its bactericidal effect. The structure of these bactericidal oligomers has not been elucidated. We here explore the feasibility of structural studies on the oligomer by solution-state NMR. To this end, we use nanodiscs that contain DMPC and DMPG, stabilized with a styrene-maleic acid copolymer that has been modified to minimize calcium chelation. We show that these nanodiscs bind daptomycin and induce the formation of stable oligomers under physiologically relevant conditions. The findings suggest that this membrane model is suitable for structural and functional characterization of oligomeric daptomycin, and possibly of other calcium-dependent lipopeptide antibiotics. We show that these nanodiscs bind daptomycin and induce the formation of stable oligomers, under conditions that are suitable for biomolecular NMR. The findings suggest that this membrane model is suitable for structural elucidation of oligomeric daptomycin, and possibly of other calcium-dependent lipopeptide antibiotics. The influence of several antimicrobial trivalent cyclic hexapeptides on the mixing behavior of bilayer lipid membranes containing phosphatidylglycerol (PG) and phosphatidylethanolamine (PE) with varying composition was studied using DSC and ITC. The peptides contained three arginines and three aromatic amino acids and had different sequences. All of them induce clustering of PG-rich clusters with bound peptides after binding. In a previous publication we could show that a correlation between clustering efficacy and the antimicrobial activity of the peptides exists (S. Finger et al., Biochim. Biophys. Acta 1848 (2015) 2998-3006). In the current study we investigated whether the non-ideality of the lipid mixture had any effect on the clustering efficacy and the critical peptide/lipid clustering ratio. We could show that for PG/PE membranes containing 11 M ratios and lipids with equal or unequal chain lengths, the amount of clustered PG depended only slightly on the absolute chain length and on the chain length re of the cyclic peptide influences the clustering efficacy but also the mixing behavior of the lipids in the bilayers has an influence on the amount of clustering induced by binding of cyclic peptides. OBJECTIVE To examine if eight weeks of high-intensity interval training (HIIT) in addition to standard care would increase and maintain peak oxygen uptake (VO2peak) more than standard care alone in patients with stroke. DESIGN This was a single-blind, multicenter, parallel group, randomized controlled trial. SETTING Specialized rehabilitation units at three Norwegian hospitals. PARTICIPANTS Participants, three months to five years after first-ever stroke, were randomly assigned to the intervention group (n=36) or the control group (n=34), 42% women, mean (SD) age was 57.6 (9.3) years and 26.4 (14.5) months post-stroke. INTERVENTION The intervention was eight weeks, three times a week high-intensity interval treadmill training with work periods of 4×4 minutes at 85-95% of peak heart rate (HRpeak), interspersed with 3 minutes of active recovery at 50-70% of HRpeak. The control group received standard care according to national guidelines. OUTCOMES The primary outcome, analyzed by intention-to-treat, was VO2peak measured as liters per minute (L·min-1) 12 months after inclusion. Secondary outcome measures were blood pressure and blood profile. RESULTS Mean (SD) baseline VO2peak was 2.63 (1.08) versus 2.87 (0.71) L·min-1, while at 12 months VO2peak was 2.70 (1.00) versus 2.67 (0.76) L·min-1, p=0.068, in the intervention and control groups, respectively. There was a significant and greater improvement in the intervention group compared to the control group at 12 months in three out of six secondary outcomes from the peak test, but no significant differences for the blood pressure or blood profile. CONCLUSIONS The HIIT intervention, which was well-tolerated in this sample of well-functioning stroke survivors, was not superior to standard care in improving and maintaining VO2peak at the 12-month follow-up. However, secondary results from the peak test showed a significant improvement from before to immediately after the intervention. OBJECTIVE To investigate the feasibility and benefits of Whole Body Vibration (WBV) exercise as a safe and effective training-tool for countering sarcopenia and age-related declines in mobility and function in the frail elderly. Linrodostat mouse DESIGN An open, randomised control trial. SETTING Residential care-facilities PARTICIPANTS 117 male and female volunteers (82.5 ± 7.9 years) INTERVENTIONS After pre-screening for contra-indications, participants were randomly allocated to a Control (CON), Simulated-WBV (SIM) or WBV-exercise (WBV) group. All participants received regular care, whilst WBV- and SIM- participants also underwent thrice-weekly exercise sessions for 16 weeks. Delivered by overload principle, WBV-training began with 5 x 1-min bouts at 6 Hz/2 mm (11min exerciserest), progressing to 10 x 1-min at up-to 26 Hz/4 mm, maintaining knee-flexion. Training for SIM participants mimicked WBV-exercise stance and duration only MAIN OUTCOME MEASURES Timed-Up-and-Go, Parallel Walk and 10-m Timed-Walk test performance were assessed, in addition to the Barthel Index Questionnaire, at baseline, 8- and 16-weeks of exercise, and 3-, 6- and 12-months post-exercise. RESULTS High levels of compliance were reported in SIM (89%) and WBV-training (93%), with ease-of-use and no adverse effects. In comparison to baseline-levels, WBV-training elicited clinically-important treatment-effects in all parameters compared to SIM and CON groups. Treatment-effects remained apparent up-to 12-months post-intervention for Parallel Walk and 6-months for 10-m Timed-Walk. Functional-test performance declined during- and post-intervention in non-WBV groups. CONCLUSIONS Findings indicate that 16-weeks of low-level WBV-exercise provides easily-accessible, adequate stimulus for the frail elderly to attain improved levels of physical functionality.