Inhibition of proteasome rescues a pathogenic variant of respiratory chain assembly factor COA7.

Nuclear and mitochondrial genome mutations lead to various mitochondrial diseases, many of which affect the mitochondrial respiratory chain. The proteome of the intermembrane space (IMS) of mitochondria consists of several important assembly factors that participate in the biogenesis of mitochondrial respiratory chain complexes. The present study comprehensively analyzed a recently identified IMS protein cytochrome c oxidase assembly factor 7 (COA7), or RESpiratory chain Assembly 1 (RESA1) factor that is associated with a rare form of mitochondrial leukoencephalopathy and complex IV deficiency. We found that COA7 requires the mitochondrial IMS import and assembly (MIA) pathway for efficient accumulation in the IMS We also found that pathogenic mutant versions of COA7 are imported slower than the wild-type protein, and mislocalized proteins are degraded in the cytosol by the proteasome. Interestingly, proteasome inhibition rescued both the mitochondrial localization of COA7 and complex IV activity in patient-derived fibroblasts. We propose proteasome inhibition as a novel therapeutic approach for a broad range of mitochondrial pathologies associated with the decreased levels of mitochondrial proteins.Narodowe Centrum Nauki (NCN) NCN 2012/05/B/NZ3/00781NCN 2015/19/B/NZ3/03272 Deutsche Forschungsgemeinschaft (DFG) SFB1190 (P13) Fundacja na rzecz Nauki Polskiej (FNP) TEAM TECH CORE FACILITY/2016‐2/2MAB/2017/2COP/01/2016 Ministerstwo Nauki i Szkolnictwa Wyższego (MNiSW) Ideas Plus programme 000263 RCUK|Medical Research Council (MRC) MC_UU_00015/5 EC|FP7|FP7 Ideas: European Research Council (FP7 Ideas) FP7‐322424339580 Institut de France Telethon Italy GTB1200

A Comparison of 3D and 2D FE Frictional Heating Models for Long and Variable Applications of Railway Tread Brake

The article proposes two 3D and 2D numerical FE models of frictional heating for the estimation of temperature distributions in railway tread brake in 1xBg configuration during repeated long-term braking. The results of computations were compared with the time courses of temperature measured using thermocouples throughout the duration of the tests on a full-scale dynamometer for two different brake shoe materials in combination with a steel wheel. The resulting temperature distributions calculated using the proposed models agreed well with the experimental measurements, and the maximum difference in temperature values does not exceed 20%. It has been proven that 2D FE model can be as efficient as 3D model to estimate the temperature distribution during long-term and variable braking in the considered friction node. The differences in the calculation of the temperature values using these models did not exceed 3%, and the calculation time for the 2D model, compared to the 3D model, was shorter approximately 85 times for the braking cycle lasting 5032 s, and approximately 45 times for the braking cycle lasting 3297 s

Protein trafficking at the crossroads to mitochondria

AbstractMitochondria are central power stations in the cell, which additionally serve as metabolic hubs for a plethora of anabolic and catabolic processes. The sustained function of mitochondria requires the precisely controlled biogenesis and expression coordination of proteins that originate from the nuclear and mitochondrial genomes. Accuracy of targeting, transport and assembly of mitochondrial proteins is also needed to avoid deleterious effects on protein homeostasis in the cell. Checkpoints of mitochondrial protein transport can serve as signals that provide information about the functional status of the organelles. In this review, we summarize recent advances in our understanding of mitochondrial protein transport and discuss examples that involve communication with the nucleus and cytosol

Massively-multiplexed generation of Bell-type entanglement using a quantum memory

High-rate generation of hybrid photon-matter entanglement remains a fundamental building block of quantum network architectures enabling protocols such as quantum secure communication or quantum distributed computing. While a tremendous effort has been made to overcome technological constraints limiting the efficiency and coherence times of current systems, an important complementary approach is to employ parallel and multiplexed architectures. Here we follow this approach experimentally demonstrating the generation of bipartite polarization-entangled photonic states across more than 500 modes, with a programmable delay for the second photon enabled by qubit storage in a wavevector multiplexed cold-atomic quantum memory. We demonstrate Clauser, Horne, Shimony, Holt inequality violation by over 3 standard deviations, lasting for at least 45 {\mu}s storage time for half of the modes. The ability to shape hybrid entanglement between the polarization and wavevector degrees of freedom provides not only multiplexing capabilities but also brings prospects for novel protocols

Superradiant parametric conversion of spin waves

Atomic-ensemble spin waves carrying single-photon Fock states exhibit nonclassical many-body correlations in-between atoms. The same correlations are inherently associated with single-photon superradiance, forming the basis of a plethora of quantum light-matter interfaces. We devise a scheme allowing the preparation of spatially-structured superradiant states in the atomic two-photon cascade using spin-wave light storage. We thus show that long-lived atomic ground-state spin waves can be converted to photon pairs opening the way towards nonlinear optics of spin waves via multi-wave mixing processes.Comment: 9 pages, 6 figure