M19 Modulates Skeletal Muscle Differentiation and Insulin Secretion in Pancreatic β-Cells through Modulation of Respiratory Chain Activity

Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion

Spreading continents kick-started plate tectonics

International audienceStresses acting on cold, thick and negatively buoyant oceanic litho- sphere are thought to be crucial to the initiation of subduction and the operation of plate tectonics, which characterizes the present- day geodynamics of the Earth. Because the Earth’s interior was hotter in the Archaean eon, the oceanic crust may have been thicker, thereby making the oceanic lithosphere more buoyant than at present, and whether subduction and plate tectonics occurred during this time is ambiguous, both in the geological record and in geodynamic models. Here we show that because the oceanic crust was thick and buoyant5, early continents may have produced intra-lithospheric gravitational stresses large enough to drive their gravitational spreading, to initiate subduction at their margins and to trigger episodes of subduction. Our model predicts the co-occurrence of deep to progressively shallower mafic volcanics and arc magmatism within continents in a self-consistent geodynamic framework, explaining the enigmatic multimodal volcanism and tectonic record of Archaean cratons. Moreover, our model predicts a petrological stratification and tectonic structure of the sub-continental lithospheric mantle, two predictions that are consistent with xenolith and seismic studies, respectively, and consistent with the existence of a mid-lithospheric seismic discontinuity. The slow gravitational collapse of early continents could have kick-started transient episodes of plate tectonics until, as the Earth’s interior cooled and oceanic lithosphere became heavier, plate tectonics became self-sustaining

On the Complexity of Compressing Obfuscation

Indistinguishability obfuscation has become one of the most exciting cryptographic primitives due to its far reaching applications in cryptography and other fields. However, to date, obtaining a plausibly secure construction has been an illusive task, thus motivating the study of seemingly weaker primitives that imply it, with the possibility that they will be easier to construct. In this work, we provide a systematic study of compressing obfuscation, one of the most natural and simple to describe primitives that is known to imply indistinguishability obfuscation when combined with other standard assumptions. A compressing obfuscator is roughly an indistinguishability obfuscator that outputs just a slightly compressed encoding of the truth table. This generalizes notions introduced by Lin et al.~(PKC 2016) and Bitansky et al.~(TCC 2016) by allowing for a broader regime of parameters. We view compressing obfuscation as an independent cryptographic primitive and show various positive and negative results concerning its power and plausibility of existence, demonstrating significant differences from full-fledged indistinguishability obfuscation. First, we show that as a cryptographic building block, compressing obfuscation is weak. In particular, when combined with one-way functions, it cannot be used (in a black-box way) to achieve public-key encryption, even under (sub-)exponential security assumptions. This is in sharp contrast to indistinguishability obfuscation, which together with one-way functions implies almost all cryptographic primitives. Second, we show that to construct compressing obfuscation with perfect correctness, one only needs to assume its existence with a very weak correctness guarantee and polynomial hardness. Namely, we show a correctness amplification transformation with optimal parameters that relies only on polynomial hardness assumptions. This implies a universal construction assuming only polynomially secure compressing obfuscation with approximate correctness. In the context of indistinguishability obfuscation, we know how to achieve such a result only under sub-exponential security assumptions together with derandomization assumptions. Lastly, we characterize the existence of compressing obfuscation with \emph{statistical} security. We show that in some range of parameters and for some classes of circuits such an obfuscator exists, whereas it is unlikely to exist with better parameters or for larger classes of circuits. These positive and negative results reveal a deep connection between compressing obfuscation and various concepts in complexity theory and learning theory

STEADY-STATE TRANSCRIPT LEVELS OF CYTOCHROME-C-OXIDASE GENES DURING HUMAN MYOGENESIS INDICATE SUBUNIT SWITCHING OF SUBUNIT VIA AND COEXPRESSION OF SUBUNIT VIIA ISOFORMS

Steady-state levels of the mitochondrial rRNAs, of mRNAs for mitochondrially and nuclear-encoded subunits of cytochrome c oxidase and for the beta-subunit of ATP synthase were assessed by Northern blot hybridizations during the in vitro differentiation of human myoblasts. Transcript levels of the so-called liver-type form of subunit VIa of cytochrome c oxidase diminished during the course of differentiation, while transcription of the so-called heart-type form was induced. Transcripts for the liver-type form and for the heart-type form of subunit VIIa of cytochrome c oxidase were detected in all myogenic cultures; the levels of the heart-type form progressively increased during the course of differentiation. The levels of the other transcripts studied did not change substantially. The results suggest subunit switching of subunit VIa and co-expression of subunit VIIa isoforms during myogenesis. The differential changes in mRNA levels of the heart-type subunits VIa and VIIa and the differential changes in mRNA levels of the liver-type subunits VIa and VIIa demonstrate that different transcriptional regulation mechanisms are present for both heart-type genes as well as for both liver-type genes