Regulation of mitochondrial proteostasis by the proton gradient

Mitochondria adapt to different energetic demands reshaping their proteome. Mitochondrial proteases are emerging as key regulators of these adaptive processes. Here, we use a multi-proteomic approach to demonstrate regulation of the m-AAA protease AFG3L2 by the mitochondrial proton gradient, coupling mitochondrial protein turnover to the energetic status of mitochondria. We identify TMBIM5 (previously also known as GHITM or MICS1) as a Ca2+/H+ exchanger in the mitochondrial inner membrane, which binds to and inhibits the m-AAA protease. TMBIM5 ensures cell survival and respiration, allowing Ca2+ efflux from mitochondria and limiting mitochondrial hyperpolarization. Persistent hyperpolarization, however, triggers degradation of TMBIM5 and activation of the m-AAA protease. The m-AAA protease broadly remodels the mitochondrial proteome and mediates the proteolytic breakdown of respiratory complex I to confine ROS production and oxidative damage in hyperpolarized mitochondria. TMBIM5 thus integrates mitochondrial Ca2+ signaling and the energetic status of mitochondria with protein turnover rates to reshape the mitochondrial proteome and adjust the cellular metabolism.

Shakedown strength based parameter optimization technique and its application on designing an airtight module

Structural optimal design is traditionally performed according to the elastic limit rule which makes the structure overweighted or strength over conservative to an extent. Shakedown theory is implemented in the present study in order to measure load-capacity performance of structure. It can determine the strength of a structure under arbitrary varying loads without loading history where failure form of incremental collapse, ratcheting and alternate plasticity will be avoided. The current research subsequently provides a parameter optimal design scheme with respect to maximum structure strength and strength-to-weight performance in the framework of shakedown which makes the optimal structure design in a relatively practical way. With this motivation, the formula of proposed shakedown limited parameter optimization problem is derived and solved based on genetic-gradient coupling algorithm. The present coupling algorithm is essentially solve a double-loop problem where the inner loop adopt interior point method to solve shakedown problem under a given parameter combination while the outer loop use genetic algorithm to find the optimal parameters based on a given shakedown fitness. In addition, external database technique is applied to accelerate computation and prevent unexpected interrupt. Subsequently, a test example which is a optimal parameter design problem of plate with a circular hole is presented to demonstrate the accuracy and effectiveness of the proposed method and algorithm. In addition, the proposed method is also utilized to determine the optimal load-bearing capacity of a airtight module to be used in a manned spacecraft. Moreover, optimal shakedown load design results of the manned airtight module as well as optimal strength-to-weight efficiency design results are given in the end. This study confirmed that genetic-gradient coupling algorithm is a effective means for determine the optimal parameter in accordance to the shakedown load domain.

Shakedown strength based parameter optimization technique and its application on designing an airtight module

Structural optimal design is traditionally performed according to the elastic limit rule which makes the structure overweighted or strength over conservative to an extent. Shakedown theory is implemented in the present study in order to measure load-capacity performance of structure. It can determine the strength of a structure under arbitrary varying loads without loading history where failure form of incremental collapse, ratcheting and alternate plasticity will be avoided. The current research subsequently provides a parameter optimal design scheme with respect to maximum structure strength and strength-to-weight performance in the framework of shakedown which makes the optimal structure design in a relatively practical way. With this motivation, the formula of proposed shakedown limited parameter optimization problem is derived and solved based on genetic-gradient coupling algorithm. The present coupling algorithm is essentially solve a double-loop problem where the inner loop adopt interior point method to solve shakedown problem under a given parameter combination while the outer loop use genetic algorithm to find the optimal parameters based on a given shakedown fitness. In addition, external database technique is applied to accelerate computation and prevent unexpected interrupt. Subsequently, a test example which is a optimal parameter design problem of plate with a circular hole is presented to demonstrate the accuracy and effectiveness of the proposed method and algorithm. In addition, the proposed method is also utilized to determine the optimal load-bearing capacity of a airtight module to be used in a manned spacecraft. Moreover, optimal shakedown load design results of the manned airtight module as well as optimal strength-to-weight efficiency design results are given in the end. This study confirmed that genetic-gradient coupling algorithm is a effective means for determine the optimal parameter in accordance to the shakedown load domain.

Comparison of coupling methods in joint inversion along the Namibian continental margin

<p>Understanding the driving mechanisms of continental breakup is still a key question in global geodynamics. The Namibian continental margin and Walvis Ridge offer an ideal area for related studies, because it accumulates on- and offshore magmatic features, associated with crustal stretching, a potential plume impact, and continental breakup.</p><p> </p><p>While previous studies in the area all agree on the general occurrence of these features, they have shown some contradictory results for their extent and depth. Therefore, we jointly invert different geophysical data sets to gain a deeper, three-dimensional insight into the continent-ocean-transition zone. In this study, we test three different cross-gradient coupling approaches for Magnetotelluric, Gravity and Seismic data sets or models. First, a fixed 3D density model is used as a structural constraint to MT data inversion. It’s impact is limited, due to large model areas with constant density values, and thus zero density gradients. Second, satellite gravity and MT data are jointly inverted. Both data sets reach a satisfactory misfit and the gravity data constraint slightly modifies the interpreted earth model. Third, a fixed 2D velocity model is used as a structural constraint for a 3D MT data inversion. Some assumptions had to be made to account for the dimensionality difference, but a sufficiently good data fit was achieved, and inversion benefits from a gradient structural model for the cross-gradient coupling. Earth model modifications through this velocity model constraint resemble the results from the joint Gravity-MT data inversion. The analysis of the three approaches, yields new insights into the cross-gradient coupling concept for joint inversion.</p><p> </p><p>Interpreting these three earth models, we believe, that continental break-up in the South Atlantic is neither driven solely by a large plume, nor by pure tectonic forces. High resistivites, velocities and densities in the lower crust point to an accumulation of plume material. However, the size of these features is not big enough to explain the Gondawana break-up as a result of a mega-plume arrival. Indications for a tectonically driven break-up initiation include evidence for extensive crustal stretching, and often an abrupt change to oceanic regime, with the upwelling asthenosphere in juxtaposition to the stretched continental lithosphere. As our models indicate a broader transitional zone, we exclude a pure tectonically driven continental break-up. Our favoured explanation incorporates aspects of both hypothesis, where an accumulation of so-called secondary plumes initiate rifting and break-up. These would be smaller plumes, rising from mid-mantle depths, which might have a common source in the deep mantle.</p>