Characterization of Mitochondrial Calcium Uniporter in Barth Syndrome Models

The Barth Syndrome (BTHS) is caused by the loss of the mitochondrial acyltransferase tafazzin, which is involved in the remodeling process of the hallmark mitochondrial glycerophospholipid cardiolipin. Cardiolipin maintains the stability of various mitochondrial protein complexes, such as respiratory chain complexes and translocases. Our analyses indicate that cardiolipin remodeling plays a crucial role in mitochondrial calcium homeostasis via the Mitochondrial Calcium Uniporter (MCU). MCU is both, a calcium-sensing and a calcium-conducting channel mediating mitochondrial calcium uptake. The mammalian MCU complex consists of the pore-forming subunit MCU, the regulatory constituents MICU1, MICU2 and EMRE, which enable the transition of calcium sensing via MICU1/2 and calcium transduction across the MCU-EMRE-containing pore in the inner mitochondrial membrane. Our current work demonstrates that the assembly and stability of MCU complexes of various molecular weight forms depend on tafazzin function. Using genetic ablation of tafazzin in TAZ KO MEF cells and organs from the BTHS mouse model, we identified three different EMRE-containing MCU oligomers in MEF cells, which undergo a complex ratio shift from WT to TAZ KO MEF mitochondria. Only one of the MCU complexes contains MICU1, which disassembles in TAZ KO MEF cells. This observation correlates with increased basal mitochondrial calcium uptake in TAZ KO MEF cells. Moreover, MCU complexes in BTHS mouse skeletal muscle and brain display similar alterations in complex organization as well. However, MCU complexes are not affected in BTHS mouse hearts, whereas MCU protein levels are reduced. The loss of MCU was recapitulated in BTHS patient-derived cardiomyocytes. Protein steady state levels of MCU in TAZ KO MEF cells are unaffected, whereas the in-vitro import of MCU into purified mitochondria of TAZ KO MEF cells is diminished. Our data display that a reduction of mitochondrial membrane potential affects the in-vitro import of MCU, indicating that MCU precursor import is more sensitive to membrane potential in comparison to control substrates EMRE and OTC. We conclude from our data that the lack of tafazzin function affects the structural integrity of MCU complexes and mitochondrial calcium metabolism

Dual Use of Liquid Hydrogen in a Next-Generation PEMFC-Powered Regional Aircraft with Superconducting Propulsion

In this paper, we present a comprehensive model framework for a disruptive cryo-electric propulsion system intended for a hydrogen-powered regional aircraft. The main innovation lies in the systematic treatment of all the electrical and thermal components to model the overall system performance. One of the main objectives is to study the feasibility of using the liquid hydrogen (LH2) fuel to provide cryogenic cooling to the cryo-electric propulsion system, and thereby enable ultracompact designs. Another aim has been to identify the optimal working point of the fuel cell to minimize the overall propulsion system’s mass. The full mission profile is evaluated to make the analysis as realistic as possible. Analyses are done for three different 2035 scenarios, where available data from the literature are projected to a baseline, conservative, and optimistic scenario. The results show that the total propulsion system’s power density can be as high as 1.63 kW/kg in the optimistic scenario and 0.79 kW/kg in the baseline scenario. In the optimistic scenario, there is also sufficient cryogenic cooling capacity in the hydrogen to secure proper conditions for all components, whereas the DC/DC converter falls outside the defined limit of 110 K in the baseline scenario.Dual Use of Liquid Hydrogen in a Next-Generation PEMFC-Powered Regional Aircraft with Superconducting PropulsionacceptedVersio

Metaxa : a software tool for automated detection and discrimination among ribosomal small subunit (12S/16S/18S) sequences of archaea, bacteria, eukaryotes, mitochondria, and chloroplasts in metagenomes and environmental sequencing datasets

Peer reviewedPostprin

Design of a Power-Dense Aviation Motor With a Low-Loss Superconducting Slotted Armature

This article describes the design and analysis of a 2.5-MW, 5000-rpm electric motor with a slotted armature employing REBCO high-temperature superconductors (HTS). The alternating current and field in the armature induces AC losses in the superconductors, requiring cryogenic cooling. Therefore, the aim is to design a machine with sufficiently low losses to make this cooling realistic, which simultaneously outperforms the state-of-the-art. The reasoning behind the key design choices is presented before the model used for two-dimensional (2-D) finite element analysis (FEA) is described. Then, HTS AC losses are studied with the T-A-formulation, examining the impact of various operating conditions. Aligning the HTS tapes with the field was found to successfully reduce AC losses, while filamentization was only successful for more than 10 filaments. The final design had an active torque density of 50.9 Nm/kg and an estimated efficiency of 99.8% when the HTS are operated at 40 K.Design of a Power-Dense Aviation Motor With a Low-Loss Superconducting Slotted ArmaturepublishedVersio

Rein tension in harness trotters during on-track exercise

Horseracing is under public scrutiny with increasing demands to safeguard horse welfare. It is accepted that, as a result of bit pressure and/or equipment, mouth lesions accompany many types of horse use, including racing. However, there are currently no data available on the range of bit pressures in driven trotters. Our aim was to investigate whether rein tension (RT, proxy for bit pressures) differs among gaits, between tempo within gait, between horses and drivers, and between left/right reins. Standardbreds (n = 9), driven by experienced drivers (n = 11), performed exercise tests on a racetrack (cross-over design; total 31 tests, data available from 26 tests). Horses' motion symmetry was measured before tests (trotting in hand). Rein tension, speed and heart rate were measured during exercise. A moving-window filter was applied to RT raw data. Median, maximum and interquartile range for the estimated stride median RT were determined for each rein (left/right) and segment: walk; circling in slow trot followed by transition to faster trot; fast (racing) trot; and slowing down to walk. Mixed models were used for statistical analysis. Least square means for segment median RT ranged between 17-19 N in walk, 34-40 N during circling-accelerating, 51-62 N in fast trot, and 53-71 N for slowing down. Segment maximum RT was between 60-81 N in walk, 104-106 N during circling-accelerating, 72-86 N in fast trot, and 86-129 N during slowing down. Interquartile ranges were between 7-9 N in walk, 28-31 N during circling-accelerating, 8-10 N in fast trot, and 12-18 N for slowing down. Hind limb asymmetry exceeded the recommended threshold in three horses and was associated with higher median (48 N) and maximum (106 N) RT than symmetric horses (29 N and 73 N, respectively, p < 0.01). Consistent left-right asymmetry in RT was more common among horses than among drivers. Rein tension increased with increasing heart rate (p <= 0.0006). Rein tensions were higher than those reported during riding or in horses worked from the ground. The findings of high RT, taken together with the high reported prevalence of oral injuries in harness trotters, call for further research into RT, motion symmetry and use of equipment

Rein tension in harness trotters during on-track exercise

Horseracing is under public scrutiny with increasing demands to safeguard horse welfare. It is accepted that, as a result of bit pressure and/or equipment, mouth lesions accompany many types of horse use, including racing. However, there are currently no data available on the range of bit pressures in driven trotters. Our aim was to investigate whether rein tension (RT, proxy for bit pressures) differs among gaits, between tempo within gait, between horses and drivers, and between left/right reins. Standardbreds (n = 9), driven by experienced drivers (n = 11), performed exercise tests on a racetrack (cross-over design; total 31 tests, data available from 26 tests). Horses\u27 motion symmetry was measured before tests (trotting in hand). Rein tension, speed and heart rate were measured during exercise. A moving-window filter was applied to RT raw data. Median, maximum and interquartile range for the estimated stride median RT were determined for each rein (left/right) and segment: walk; circling in slow trot followed by transition to faster trot; fast (racing) trot; and slowing down to walk. Mixed models were used for statistical analysis. Least square means for segment median RT ranged between 17–19 N in walk, 34–40 N during circling-accelerating, 51–62 N in fast trot, and 53–71 N for slowing down. Segment maximum RT was between 60–81 N in walk, 104–106 N during circling-accelerating, 72–86 N in fast trot, and 86–129 N during slowing down. Interquartile ranges were between 7–9 N in walk, 28–31 N during circling-accelerating, 8–10 N in fast trot, and 12–18 N for slowing down. Hind limb asymmetry exceeded the recommended threshold in three horses and was associated with higher median (48 N) and maximum (106 N) RT than symmetric horses (29 N and 73 N, respectively, p &lt; 0.01). Consistent left-right asymmetry in RT was more common among horses than among drivers. Rein tension increased with increasing heart rate (p ≤ 0.0006). Rein tensions were higher than those reported during riding or in horses worked from the ground. The findings of high RT, taken together with the high reported prevalence of oral injuries in harness trotters, call for further research into RT, motion symmetry and use of equipment

What do we learn from correlations of local and global network properties?

In complex networks a common task is to identify the most important or "central" nodes. There are several definitions, often called centrality measures, which often lead to different results. Here we study extensively correlations between four local and global measures namely the degree, the shortest-path-betweenness, the random-walk betweenness and the subgraph centrality on different random-network models like Erdos-Renyi, Small-World and Barabasi-Albert as well as on different real networks like metabolic pathways, social collaborations and computer networks. Correlations are quite different between the real networks and the model networks questioning whether the models really reflect all important properties of the real world