Constant force muscle stretching induces greater acute deformations and changes in passive mechanical properties compared to constant length stretching

Stretching is applied to lengthen shortened muscles in pathological conditions such as joint contractures. We investigated (i) the acute effects of different types of stretching, i.e. constant length (CL) and constant force (CF) stretching, on acute deformations and changes in passive mechanical properties of medial gastrocnemius muscle (MG) and (ii) the association of acute muscle–tendon deformations or changes in mechanical properties with the impulse or maximal strain of stretching. Forty-eight hindlimbs from 13 male and 12 female Wistar rats (13 weeks old, respectively 424.6 ± 35.5 and 261.8 ± 15.6 g) were divided into six groups (n = 8 each). The MG was initially stretched to a length at which the force was 75%, 95%, or 115% of the force corresponding to estimated maximal dorsiflexion and held at either CF or CL for 30 min. Before and after the stretching protocol, the MG peak force and peak stiffness were assessed by lengthening the passive muscle to the length corresponding to maximal ankle dorsiflexion. Also, the muscle belly length and tendon length were measured. CF stretching affected peak force, peak stiffness, muscle belly length, and tendon length more than CL stretching (p &lt; 0.01). Impulse was associated only with the decrease in peak force, while maximal strain was associated with the decrease in peak force, peak stiffness, and the increase in muscle belly length. We conclude that CF stretching results in greater acute deformations and changes in mechanical properties than CL stretching, which appears to be dependent predominantly on the differences in imposed maximal strain.</p

Novel RNA interactions with the elongation factor EF-Tu: consequences for protein synthesis and tuf gene expression

Microbial Biotechnolog

Decreased Pain and Improved Dynamic Knee Instability Mediate the Beneficial Effect of Wearing a Soft Knee Brace on Activity Limitations in Patients With Knee Osteoarthritis

OBJECTIVE: To evaluate whether improvement of proprioception, pain or dynamic knee instability mediate the effect of wearing a soft knee brace on activity limitations in persons with knee osteoarthritis (OA). METHODS: Exploratory analysis from 44 participants with knee OA and self-reported knee instability in a laboratory trial evaluating the effect of wearing a commercially available soft knee brace. Activity limitations were assessed with the 10-meter walk test and the Get up and Go test. Knee joint proprioception was assessed by an active joint position sense test; pain was assessed with the Numeric Rating Scale (NRS); pressure pain threshold (PPT) was assessed with a hand-held pressure algometer; dynamic knee instability was expressed by the Perturbation Response, i.e. a measure reflecting a deviation in mean knee varus-valgus angle after a controlled mechanical perturbation on a treadmill, with respect to level walking. Mediation analysis was conducted with the product of coefficients approach. Confidence intervals were calculated with a bootstrap procedure. RESULTS: A decrease of pain (NRS) and a decrease of dynamic knee instability mediated the effect of wearing a soft knee brace on reduction of activity limitations (p < 0.05), while changes of proprioception and PPT did not mediate this effect (p > 0.05). CONCLUSION: This study shows that decreased pain and reduced dynamic knee instability are pathways via which wearing a soft knee brace decreased activity limitations in persons with knee OA. This article is protected by copyright. All rights reserved

Synthesis of Stable NAD+ Mimics as Inhibitors for the Legionella pneumophila Phosphoribosyl Ubiquitylating Enzyme SdeC

Stable NAD+ analogues carrying single atom substitutions in either the furanose ring or the nicotinamide part have proven their value as inhibitors for NAD+‐consuming enzymes. To investigate the potential of such compounds to inhibit the adenosine diphosphate ribosyl (ADPr) transferase activity of the Legionella SdeC enzyme, we prepared three NAD+ analogues, namely carbanicotinamide adenosine dinucleotide (c‐NAD+), thionicotinamide adenosine dinucleotide (S‐NAD+) and benzamide adenosine dinucleotide (BAD). We optimized the chemical synthesis of thionicotinamide riboside and for the first time used an enzymatic approach to convert all three ribosides into the corresponding NAD+ mimics. We thus expanded the known scope of substrates for the NRK1/NMNAT1 enzyme combination by turning all three modified ribosides into NAD+ analogues in a scalable manner. We then compared the three NAD+ mimics side‐by‐side in a single assay for enzyme inhibition on Legionella effector enzyme SdeC. The class of SidE enzymes to which SdeC belongs was recently identified to be important in bacterial virulence, and we found SdeC to be inhibited by S‐NAD+ and BAD with IC50 values of 28 and 39 μM, respectively.Bio-organic Synthesi

Limb Spicules from the Ground and from Space

We amassed statistics for quiet-sun chromosphere spicules at the limb using ground-based observations from the Swedish 1-m Solar Telescope on La Palma and simultaneously from NASA's Transition Region and Coronal Explorer (TRACE) spacecraft. The observations were obtained in July 2006. With the 0.2 arcsecond resolution obtained after maximizing the ground-based resolution with the Multi-Object Multi-Frame Blind Deconvolution (MOMFBD) program, we obtained specific statistics for sizes and motions of over two dozen individual spicules, based on movies compiled at 50-second cadence for the series of five wavelengths observed in a very narrow band at H-alpha, on-band and in the red and blue wings at 0.035 nm and 0.070 nm (10 s at each wavelength) using the SOUP filter, and had simultaneous observations in the 160 nm EUV continuum from TRACE. The MOMFBD restoration also automatically aligned the images, facilitating the making of Dopplergrams at each off-band pair. We studied 40 H-alpha spicules, and 14 EUV spicules that overlapped H-alpha spicules; we found that their dynamical and morphological properties fit into the framework of several previous studies. From a preliminary comparison with spicule theories, our observations are consistent with a reconnection mechanism for spicule generation, and with UV spicules being a sheath region surrounding the H-alpha spicules

Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI) versus intercalated TKI with chemotherapy for EGFR-mutated nonsmall cell lung cancer

Introduction Previous studies have shown interference between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy in the cell cycle, thus reducing efficacy. In this randomised controlled trial we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR-mutated nonsmall cell lung cancer (NSCLC). Materials and methods Treatment-naïve patients with an activating EGFR mutation, ECOG performance score of 0–3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2–16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival, objective response rate (ORR) and toxicity. Results Between April 2014 and September 2016, 22 patients were randomised equally into both arms; the study was stopped due to slow accrual. Median follow-up was 64 months. Median PFS was 13.7 months (95% CI 5.2–18.8) for CPE and 10.3 months (95% CI 7.1–15.5; hazard ratio (HR) 0.62, 95% CI 0.25–1.57) for erlotinib monotherapy; when compensating for number of days receiving erlotinib, PFS of the CPE arm was superior (HR 0.24, 95% CI 0.07–0.83; p=0.02). ORR was 64% for CPE versus 55% for erlotinib monotherapy. Median overall survival was 31.7 months (95% CI 21.8–61.9 months) for CPE compared to 17.2 months (95% CI 11.5–45.5 months) for erlotinib monotherapy (HR 0.58, 95% CI 0.22–1.41 months). Patients treated with CPE had higher rates of treatment-related fatigue, anorexia, weight loss and renal toxicity. Conclusion Intercalating erlotinib with cisplatin-pemetrexed provides a longer PFS compared to erlotinib alone in EGFR-mutated NSCLC at the expense of more toxicity

The helminth glycoprotein omega-1 improves metabolic homeostasis in obese mice through type 2 immunity-independent inhibition of food intake

Type 2 immunity plays an essential role in the maintenance of metabolic homeostasis and its disruption during obesity promotes meta-inflammation and insulin resistance. Infection with the helminth parasite Schistosoma mansoni and treatment with its soluble egg antigens (SEA) induce a type 2 immune response in metabolic organs and improve insulin sensitivity and glucose tolerance in obese mice, yet, a causal relationship remains unproven. Here, we investigated the effects and underlying mechanisms of the T2 ribonuclease omega-1 (omega 1), one of the major S mansoni immunomodulatory glycoproteins, on metabolic homeostasis. We show that treatment of obese mice with plant-produced recombinant omega 1, harboring similar glycan motifs as present on the native molecule, decreased body fat mass, and improved systemic insulin sensitivity and glucose tolerance in a time- and dose-dependent manner. This effect was associated with an increase in white adipose tissue (WAT) type 2 T helper cells, eosinophils, and alternatively activated macrophages, without affecting type 2 innate lymphoid cells. In contrast to SEA, the metabolic effects of omega 1 were still observed in obese STAT6-deficient mice with impaired type 2 immunity, indicating that its metabolic effects are independent of the type 2 immune response. Instead, we found that omega 1 inhibited food intake, without affecting locomotor activity, WAT thermogenic capacity or whole-body energy expenditure, an effect also occurring in leptin receptor-deficient obese and hyperphagic db/db mice. Altogether, we demonstrate that while the helminth glycoprotein omega 1 can induce type 2 immunity, it improves whole-body metabolic homeostasis in obese mice by inhibiting food intake via a STAT6-independent mechanism.Radiolog

Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review

DOT Tomography of the Solar Atmosphere VII. Chromospheric Response to Acoustic Events

We use synchronous movies from the Dutch Open Telescope sampling the G band, Ca II and Halpha with five-wavelength profile sampling to study the response of the chromosphere to acoustic events in the underlying photosphere. We first compare the visibility of the chromosphere in Ca II H and Halpha, demonstrate that studying the chromosphere requires Halpha data, and summarize recent developments in understanding why this is so. We construct divergence and vorticity maps of the photospheric flow field from the G-band images and locate specific events through the appearance of bright Ca II H grains. The reaction of the Halpha chromosphere is diagnosed in terms of brightness and Doppler shift. We show and discuss three particular cases in detail: a regular acoustic grain marking shock excitation by granular dynamics, a persistent flasher which probably marks magnetic-field concentration, and an exploding granule. All three appear to buffet overlying fibrils, most clearly in Dopplergrams. Although our diagnostic displays to dissect these phenomena are unprecedentedly comprehensive, adding even more information (photospheric Doppler tomography and magnetograms, chromospheric imaging and Doppler mapping in the ultraviolet) is warranted.Comment: accepted by Solar Physic

The European Solar Telescope

The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French Télescope Héliographique pour l'Étude du Magnétisme et des Instabilités Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems