Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G presenting as childhood-onset severe myopathy: threshold determination through segregation study

Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G is associated with respiratory chain complex I deficiency and has been described as a rare cause of mostly adult-onset slowly progressive myopathy. Five families with 11 patients have been described so far; 5 of them died young due to cardiorespiratory failure. Here, we report on a segregation study in a family with an index patient who already presented at the age of 18 months with proximal muscular hypotonia, abnormal fatigability, and lactic acidosis. This early-onset myopathy was rapidly progressive. At 8 years, the patient is wheel-chair bound, requires nocturnal assisted ventilation, and suffers from recurrent respiratory infections. Severe complex I deficiency and nearly homoplasmy for m.3302A > G were found in muscle. We collected blood, hair, buccal swabs and muscle biopsies from asymptomatic adults in this pedigree and determined heteroplasmy levels in these tissues as well as OXPHOS activities in muscle. All participating asymptomatic adults had normal OXPHOS activities. In contrast to earlier reports, we found surprisingly little variation of heteroplasmy levels in different tissues of the same individual. Up to 45% mutation load in muscle and up to 38% mutation load in other tissues were found in non-affected adults. The phenotypic spectrum of tRNA(Leu(UUR)) m.3302A > G mutation seems to be wider than previously described. A threshold of more than 45% heteroplasmy in muscle seems to be necessary to alter complex I activity leading to clinical manifestation. The presented data may be helpful for prognostic considerations and counseling in affected families.

Block training periodization in alpine skiing: effects of 11-day HIT on VO2max and performance

Attempting to achieve the high diversity of training goals in modern competitive alpine skiing simultaneously can be difficult and may lead to compromised overall adaptation. Therefore, we investigated the effect of block training periodization on maximal oxygen consumption (VO2max) and parameters of exercise performance in elite junior alpine skiers. Six female and 15 male athletes were assigned to high-intensity interval (IT, N = 13) or control training groups (CT, N = 8). IT performed 15 high-intensity aerobic interval (HIT) sessions in 11 days. Sessions were 4 x 4 min at 90-95% of maximal heart rate separated by 3-min recovery periods. CT continued their conventionally mixed training, containing endurance and strength sessions. Before and 7 days after training, subjects performed a ramp incremental test followed by a high-intensity time-to-exhaustion (tlim) test both on a cycle ergometer, a 90-s high-box jump test as well as countermovement (CMJ) and squat jumps (SJ) on a force plate. IT significantly improved relative VO2max by 6.0% (P < 0.01; male +7.5%, female +2.1%), relative peak power output by 5.5% (P < 0.01) and power output at ventilatory threshold 2 by 9.6% (P < 0.01). No changes occurred for these measures in CT. tlim remained unchanged in both groups. High-box jump performance was significantly improved in males of IT only (4.9%, P < 0.05). Jump peak power (CMJ -4.8%, SJ -4.1%; P < 0.01), but not height decreased in IT only. For competitive alpine skiers, block periodization of HIT offers a promising way to efficiently improve VO2max and performance. Compromised explosive jump performance might be associated with persisting muscle fatigue.

Properties of low-threshold motor axons in the human median nerve

This study investigated the excitability and accommodative properties of low-threshold human motor axons to test whether these motor axons have greater expression of the persistent Na(+) conductance, I(NaP). Computer-controlled threshold tracking was used to study 22 single motor units and the data were compared with compound motor potentials of various amplitudes recorded in the same experimental session. Detailed comparisons were made between the single units and compound potentials that were 40% or 5% of maximal amplitude, the former because this is the compound potential size used in most threshold tracking studies of axonal excitability, the latter because this is the compound potential most likely to be composed entirely of motor axons with low thresholds to electrical recruitment. Measurements were made of the strength-duration relationship, threshold electrotonus, current-voltage relationship, recovery cycle and latent addition. The findings did not support a difference in I(NaP). Instead they pointed to greater activity of the hyperpolarization-activated inwardly rectifying current (I(h)) as the basis for low threshold to electrical recruitment in human motor axons. Computer modelling confirmed this finding, with a doubling of the hyperpolarization-activated conductance proving the best single parameter adjustment to fit the experimental data. We suggest that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel(s) expressed on human motor axons may be active at rest and contribute to resting membrane potential.

Threshold-dependent effects on peripheral nerve in vivo excitability properties in the rat

Various factors, including maturity, have been shown to influence peripheral nerve excitability measures, but little is known about differences in these properties between axons with different stimulation thresholds. Multiple nerve excitability tests were performed on the caudal motor axons of immature and mature female rats, recording from tail muscles at three target compound muscle action potential (CMAP) levels: 10%, 40% ("standard" level), and 60% of the maximum CMAP amplitude. Compared to lower target levels, axons at high target levels have the following characteristics: lower strength-duration time constant, less threshold reduction during depolarizing currents and greater threshold increase to hyperpolarizing currents, most notably to long hyperpolarizing currents in mature rats. Threshold-dependent effects on peripheral nerve excitability properties depend on the maturation stage, especially inward rectification (Ih), which becomes inversely related to threshold level. Performing nerve excitability tests at different target levels is useful in understanding the variation in membrane properties between different axons within a nerve. Because of the threshold effects on nerve excitability and the possibility of increased variability between axons and altered electric recruitment order in disease conditions, excitability parameters measured only at the "standard" target level should be interpreted with caution, especially the responses to hyperpolarizing currents.

Corticospinal output during muscular fatigue differs in multiple sclerosis patients compared to healthy controls

In multiple sclerosis (MS), fatigue is a common and often disabling symptom. It has multiple causes with central motor fatigue playing an important role.

A Model to Predict Percolation Threshold and Effective Conductivity of Infiltrated Electrodes for Solid Oxide Fuel Cells

We present a mechanistic modeling methodology to predict both the percolation threshold and effective conductivity of infiltrated Solid Oxide Fuel Cell (SOFC) electrodes. The model has been developed to mirror each step of the experimental fabrication process. The primary model output is the infiltrated electrode effective conductivity which provides results over a range of infiltrate loadings that are independent of the chosen electronically conducting material. The percolation threshold is utilized as a valuable output data point directly related to the effective conductivity to compare a wide range of input value choices. The predictive capability of the model is demonstrated by favorable comparison to two separate published experimental studies, one using strontium molybdate and one using La0.8Sr0.2FeO3-δ as infiltrate materials. Effective conductivities and percolation thresholds are shown for varied infiltrate particle size, pore size, and porosity with the infiltrate particle size having the largest impact on the results.

A Model to Predict Percolation Threshold and Effective Conductivity of Infiltrated Electrodes for Solid Oxide Fuel Cells

We present a mechanistic modeling methodology to predict both the percolation threshold and effective conductivity of infiltrated Solid Oxide Fuel Cell (SOFC) electrodes. The model has been developed to mirror each step of the experimental fabrication process. The primary model output is the infiltrated electrode effective conductivity which provides results over a range of infiltrate loadings that are independent of the chosen electronically conducting material. The percolation threshold is utilized as a valuable output data point directly related to the effective conductivity to compare a wide range of input value choices. The predictive capability of the model is demonstrated by favorable comparison to two separate published experimental studies, one using strontium molybdate and one using La0.8Sr0.2FeO3-delta as infiltrate materials. Effective conductivities and percolation thresholds are shown for varied infiltrate particle size, pore size, and porosity with the infiltrate particle size having the largest impact on the results. (C) 2013 The Electrochemical Society. All rights reserved.