JNK activation in TA and EDL muscle is load-dependent in rats receiving identical excitation patterns

As the excitation–contraction coupling is inseparable during voluntary exercise, the relative contribution of the mechanical and neural input on hypertrophy-related molecular signalling is still poorly understood. Herein, we use a rat in-vivo strength exercise model with an electrically-induced standardized excitation pattern, previously shown to induce a load-dependent increase in myonuclear number and hypertrophy, to study acute effects of load on molecular signalling. We assessed protein abundance and specific phosphorylation of the four protein kinases FAK, mTOR, p70S6K and JNK after 2, 10 and 28 min of a low- or high-load contraction, in order to assess the effects of load, exercise duration and muscle-type on their response to exercise. Specific phosphorylation of mTOR, p70S6K and JNK was increased after 28 min of exercise under the low- and high-load protocol. Elevated phosphorylation of mTOR and JNK was detectable already after 2 and 10 min of exercise, respectively, but greatest after 28 min of exercise, and JNK phosphorylation was highly load-dependent. The abundance of all four kinases was higher in TA compared to EDL muscle, p70S6K abundance was increased after exercise in a load-independent manner, and FAK and JNK abundance was reduced after 28 min of exercise in both the exercised and control muscles. In conclusion, the current study shows that JNK activation after a single resistance exercise is load-specific, resembling the previously reported degree of myonuclear accrual and muscle hypertrophy with repetition of the exercise stimulus.

An electrophysiological measure of tonotopic selectivity in normal-hearing humans and cats

We describe a non-invasive electrophysiological (EEG) measure of tonotopic selectivity and compare the results between humans and cats. Sequences of 50-ms tone-burst probes were presented at 1-second intervals against a continuous noise masker, and the averaged cortical onset response (COR) to the probe was measured using EEG electrodes placed on the scalp. The noise masker had a bandwidth of 1 or 1/8th octave, geometrically centred on 4000 Hz for humans and 8000 Hz for cats. Probe frequency was either -0.5, -0.25, 0, 0.25 or 0.5 octaves re 4000/8000 Hz. The COR was larger for probe frequencies more distant from the noise geometrical centre, and this effect was greater for the 1/8th-octave than for the 1-octave masker. This pattern broadly reflected the masked excitation patterns obtained psychophysically with similar stimuli in a companion paper. However, the positive signal-to-noise ratio used to obtain reliable COR measures meant that some aspects of the data differed from those obtained psychophysically, in a way that could be partly explained by the upward spread of the probe’s excitation pattern. We argue that although COR measures are affected by some factors that differ from those that influence psychophysical masked detection thresholds, they can reveal differences in the width of excitation patterns produced by different stimuli. We also argue that the paradigm may be effectively applied to cochlear-implant experiments in humans and animals.

Directed graph mapping is able to distinguish between the true and false rotors in a complex in-silico excitation pattern

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Supported in part by Dirección General de Polı́tica Cientı́fica de la Generalitat Valenciana PROMETEU 2020/043 Background In realistic in-silico studies (Figure1, top row) it was shown that phase mapping PM (Figure 1, A) can detect the correct rotor as well as phantom rotors as an artefact of interpolation or due to the far field (Figure 1, B). After interpretation of the LAT, the far field detections could not be distinguished from the true rotor driving the excitation pattern. This can contribute to failure in Atrial Fibrillation (AF) ablation procedures. Objective We tested if the recently developed tool Directed Graph mapping (DGM) is less prone to far-field effects and interpolation artefacts than PM on the same in-silico data. DGM represents the excitation pattern as a directed network, from which the rotational activity is detected as cycles in that network. Methods Starting from the electrograms (EGMs) of the 64 electrode basket catheter, we interpolated to 957 equidistant electrodes and calculated local activation times (LATs) of the interpolated EGMs (Figure 1, C). We varied the minimal allowed conduction velocity and calculated the corresponding networks for the complete simulation time. Detections were considered as correct if they were located in the same region of the true core of the phasemaps. The false detections were classified in multiple different regions (Figure 1, D). Results We find that by proper choice of CVs in the graphs it is possible to achieve a 80% detection of true rotors with 26% detection of false rotors. Reducing restrictions on the CVs increased the detection rate of the false rotors. False rotors due to artifacts were not detected by DGM (Figure 1, last row). Conclusion DGM is able to distinguish between true and far field rotors. False detections due to interpolation artifacts as seen in the PM protocol were not observed. The velocity limits in the graph construction play a keyrole in eliminating the far field effects. Abstract Figure 1

JNK activation in TA and EDL muscle is load-dependent in rats receiving identical excitation patterns

ABSTACTAimAs the excitation-contraction coupling is inseparable during voluntary exercise, the relative contribution of the mechanical and neural input is poorly understood. Herein, we use a rat in-vivo strength training setup with an electrically induced standardized excitation pattern previously shown to lead to a load-dependent increase in myonuclear number and hypertrophy, to study acute effects of load per se on molecular signalling.MethodsAnaesthetized rats were subjected to unliteral identical electrically-paced contractions of the TA and EDL muscles under a high or low load for a duration of 2, 10 or 28-minutes. Muscle soluble proteins were extracted, and abundance and specific phosphorylations of FAK, mTOR, p70S6K and JNK were measured. Effects of exercise, load, muscle and exercise duration were assessed.ResultsSpecific phosphorylation of S2448-mTOR, T421/S424-p70S6K and T183/Y185-JNK was increased after 28-minutes of exercise under the high- and low-load protocol. Elevated phosphorylation of mTOR and JNK was detectable already after 2 and 10 minutes of exercise, respectively, but greatest after 28-minutes of exercise. T183/Y185-JNK and S2448-mTOR demonstrated a load-dependent increase in phosphorylation in the exercised muscles that for mTOR depended on muscle type. The abundance of all four kinases was higher in TA compared to EDL muscle. FAK and JNK abundance was reduced after 28 minutes of exercise in both the exercised and control muscle.ConclusionThe current study shows that JNK and mTOR activation is load-driven, and together with muscle-type specific mTOR and p70S6K effects it may drive muscle-type specific exercise and load-responses.

Dynamic Analysis of Low-Pressure Steam Turbine Last Stage Fir-Tree Root Blade

In the present study, the dynamic behavior of the last stage low-pressure steam turbine blade with fir-tree root at different conditions of blade root flank faces and their interfaces with rotor groove have been analyzed. Modal analysis has been done using a finite element approach to evaluate natural frequencies and evaluation of Campbell diagram generated under these conditions. For this, both healthy and defective blade have been taken. Since the variable crack size of fir-tree root flank has been taken, the excitation pattern has been evaluated due to stiffness variation of the cracked blade. This analysis provides the basis of excitation pattern of cracked blades due to inherent character and critical stressed zone. The outcome of this study forms the guidelines and checks during the fitting of blades in rotor assembly and its checks during health audit, overhaul, overspeed balancing test, and frequency turning.

A novel ex vivo protocol to mimic human walking gait: implications for Duchenne muscular dystrophy

A novel ex vivo mouse soleus protocol that mimics scaled length change and excitation profiles predicted by a mathematical model of human soleus during gait is presented. A custom stimulator was developed that enabled an innovative muscle stimulation technique to modulate voltage to closely match the excitation pattern of human soleus during gait. This ex vivo protocol provides assessment of simulated human movement in mouse muscle, including components of eccentric contractions.

P1443Accuracy of three algorithms in predicting accessory pathway localization in a pediatric population with ventricular pre-excitation

BACKGROUND Prediction of accessory pathway location is extremely important before scheduling ablation, even more in paediatric patients. Given the absence in the literature of conclusive and recent studies that established the best algorithm to predict location in these patients, especially after the introduction of 3D mapping systems, we designed a study to compare three previously published algorithms. AIM The aim of this study is to assess and compare the accuracy in predicting accessory pathway location of the algorithm by Arruda, Boersma and Chiang. METHODS This is a multicenter, observational, retrospective clinical study based on the analysis of the resting 12-leads ECGs of children (aged 0-18 years) with ventricular pre-excitation pattern. The study lasts from January 2013 to June 2019. We analyzed the accuracy (defined as percentage of true positive values) of predicted location by each algorithm, which could include one or more than one of 13 regions around mitral and tricuspid annuli. RESULTS Study population was composed by 120 patients, mean age was 12.7 +/- 3.6 years (height 155.6 +/-19.3 cm and weight 48.3 +/- 17.1 kg). The algorithm by Boersma has the highest percentage of predicted pathway locations that are found to be concordant with the site of successful AP ablation (see table). When we corrected for pre-test probability, the algorithm by Arruda makes the possibility of one specific location 8 times higher, the one by Boersma 6.4 times higher and the one by Chiang 6.9 times higher than by chance. CONCLUSIONS The algorithm by Boersma showed the highest accuracy in accessory pathway location, on the other hand the one by Arruda seems to have the highest corrected accuracy in accessory pathway among children. table 1 Arruda Boersma Chiang Number of locations 13 9 13 Total accuracy 0,617 0,717 0,533 Corrected accuracy per locations 8,0158 6,4494 6,929 Abstract Figure. picture 1