A Theoretical Model of Mitochondrial ATP Synthase Deficiencies. The Role of Mitochondrial Carriers

The m.8993T>G mutation of the mitochondrial MT-ATP6 gene is associated with NARP syndrome (neuropathy, ataxia and retinitis pigmentosa). The equivalent point mutation introduced in yeast Saccharomyces cerevisiae mitochondrial DNA considerably reduced the activity of ATP synthase and of cytochrome-c-oxidase, preventing yeast growth on oxidative substrates. The overexpression of the mitochondrial oxodicarboxylate carrier (Odc1p) was able to rescue the growth on the oxidative substrate by increasing the substrate-level phosphorylation of ADP coupled to the conversion of α-ketoglutarate (AKG) into succinate with an increase in Complex IV activity. Previous studies showed that equivalent point mutations in ATP synthase behave similarly and can be rescued by Odc1p overexpression and/or the uncoupling of OXPHOS from ATP synthesis. In order to better understand the mechanism of the ATP synthase mutation bypass, we developed a core model of mitochondrial metabolism based on AKG as a respiratory substrate. We describe the different possible metabolite outputs and the ATP/O ratio values as a function of ATP synthase inhibition.

Equivalent Point-Source Ground-Motion Model for Subduction Earthquakes in Japan

ABSTRACT We use an equivalent point-source ground-motion model (GMM) to characterize subduction earthquakes (interface and in-slab) in Japan. The model, which is calibrated using the newly published Next Generation Attenuation (NGA) Subduction database (Bozorgnia et al., 2020), provides a useful complement to the more traditional empirical NGA models developed from the same database. The utility of the point-source model approach lies in its ability to aid in the interpretation of observed trends in the data and to guide modifications to the GMM for application to other regions having fewer data. Key trends in the data that are parameterized with the model include: (a) the enrichment of high-frequency amplitudes for in-slab versus interface events, as modeled by a depth-dependent stress parameter, and (b) attenuation attributes that vary with event type and region, including consideration of fore-arc versus back-arc settings. The developed GMMs of this study are applicable for M 4.5–9.2 for interface events, and M 4–8.5 for in-slab earthquakes, for rupture distances (Drup) from 10 to 600 km, and for 100 m/s<VS30<1500 m/s (time-averaged shear-wave velocity in the top 30 m).

Considerations on the Derivative of the Titration Curve of a Weak Diacid

We show that the derivative of the titration curve of a diacid can be used to assess the first equivalent as well as the second equivalent point, but also the value for which pH=pKa. This is controlled by the difference between both pKa's of the diacid. A bifurcation is observed for the values of volume of titrant for which the first derivative cancels.<br>

Considerations on the Derivative of the Titration Curve of a Weak Diacid

We show that the derivative of the titration curve of a diacid can be used to assess the first equivalent as well as the second equivalent point, but also the value for which pH=pKa. This is controlled by the difference between both pKa's of the diacid. A bifurcation is observed for the values of volume of titrant for which the first derivative cancels.<br>