Mitochondrial effects of dexamethasone imply both membrane and cytosolic-initiated pathways in HepG2 cells

Glucocorticoid treatment is often linked to increased whole-body energy expenditure and hypermetabolism. Glucocorticoids affect mitochondrial energy production, notably in the liver, where they lead to mitochondrial uncoupling reducing the efficacy of oxidative phosphorylation. However, the signaling pathways involved in these phenomena are poorly understood. Here we treated HepG2 cells with dexamethasone for different times and, by using different combinations of inhibitors, we showed that dexamethasone treatment leads to recruitment of two main signaling pathways. The first one involves a G-protein coupled membrane glucocorticoid binding site and rapidly decreases complexes I and II activities while complex III activity is upregulated in a p38MAPK dependent mechanism. The second one implies the classical cytosolic glucocorticoid receptor and triggers long-term transcriptional increases of respiration rates and of complex IV activity and quantity. We concluded that mitochondria are the target of multiple dexamethasone-induced regulatory pathways that are set up gradually after the beginning of hormone exposure and that durably influence mitochondrial oxidative phosphorylation

The pro-region of the Kex2 endoprotease of Saccharomyces cerevisiae is removed by self-processing

AbstractWe have produced in the baculovirus/insect cells expression system a soluble secreted form of the Saccharomyces cerevisiae Kex2 endoprotease. This secreted enzyme was purified and its NH2-terminal sequence determined. The NH2-terminal sequence started at residue Leu109 of the sequence deduced from the KEX2 gene nucleotide sequence, showing that the Kex2 enzyme is produced as a proenzyme. Residue Leu109 is preceded by a pair of basic amino acid residues (Lys107-Arg108) which is a potential processing site for the Kex2 endopeptidase. Futhermore, expression of an inactive form of this truncated enzyme resulted in the production of a protein with a higher molecular weight. These observations suggest that the pro-region of Kex2 endoprotease is removed by a self-processing event

Compliance error compensation in robotic-based milling

The paper deals with the problem of compliance errors compensation in robotic-based milling. Contrary to previous works that assume that the forces/torques generated by the manufacturing process are constant, the interaction between the milling tool and the workpiece is modeled in details. It takes into account the tool geometry, the number of teeth, the feed rate, the spindle rotation speed and the properties of the material to be processed. Due to high level of the disturbing forces/torques, the developed compensation technique is based on the non-linear stiffness model that allows us to modify the target trajectory taking into account nonlinearities and to avoid the chattering effect. Illustrative example is presented that deals with robotic-based milling of aluminum alloy

Origin of volatiles in the main belt

We propose a scenario for the formation of the main belt in which asteroids incorporated icy particles formed in the outer solar nebula. We calculate the composition of icy planetesimals formed beyond a heliocentric distance of 5 au in the nebula by assuming that the abundances of all elements, in particular that of oxygen, are solar. As a result, we show that ices formed in the outer solar nebula are composed of a mix of clathrate hydrates, hydrates formed above 50 K and pure condensates produced at lower temperatures. We then consider the inward migration of solids initially produced in the outer solar nebula and show that a significant fraction may have drifted to the current position of the main belt without encountering temperature and pressure conditions high enough to vaporize the ices they contain. We propose that, through the detection and identification of initially buried ices revealed by recent impacts on the surfaces of asteroids, it could be possible to infer the thermodynamic conditions that were present within the solar nebula during the accretion of these bodies, and during the inward migration of icy planetesimals. We also investigate the potential influence that the incorporation of ices in asteroids may have on their porosities and densities. In particular, we show how the presence of ices reduces the value of the bulk density of a given body, and consequently modifies its macroporosity from that which would be expected from a given taxonomic typ

Multiphase weakly nonlinear geometric optics for Schrodinger equations

We describe and rigorously justify the nonlinear interaction of highly oscillatory waves in nonlinear Schrodinger equations, posed on Euclidean space or on the torus. Our scaling corresponds to a weakly nonlinear regime where the nonlinearity affects the leading order amplitude of the solution, but does not alter the rapid oscillations. We consider initial states which are superpositions of slowly modulated plane waves, and use the framework of Wiener algebras. A detailed analysis of the corresponding nonlinear wave mixing phenomena is given, including a geometric interpretation on the resonance structure for cubic nonlinearities. As an application, we recover and extend some instability results for the nonlinear Schrodinger equation on the torus in negative order Sobolev spaces.Comment: 29 page

Subcarrier index-power modulated optical OFDM with dual superposition multiplexing for IMDD PON systems

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Topological Analysis of Metabolic Networks Integrating Co-Segregating Transcriptomes and Metabolomes in Type 2 Diabetic Rat Congenic Series

Background: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus is caused by complex organ-specific cellular mechanisms contributing to impaired insulin secretion and insulin resistance. Methods: We used systematic metabotyping by 1H NMR spectroscopy and genome-wide gene expression in white adipose tissue to map molecular phenotypes to genomic blocks associated with obesity and insulin secretion in a series of rat congenic strains derived from spontaneously diabetic Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a network biology strategy approach to visualise shortest paths between metabolites and genes significantly associated with each genomic block. Results: Despite strong genomic similarities (95-99%) among congenics, each strain exhibited specific patterns of gene expression and metabotypes, reflecting metabolic consequences of series of linked genetic polymorphisms in the congenic intervals. We subsequently used the congenic panel to map quantitative trait loci underlying specific metabotypes (mQTL) and genome-wide expression traits (eQTL). Variation in key metabolites like glucose, succinate, lactate or 3-hydroxybutyrate, and second messenger precursors like inositol was associated with several independent genomic intervals, indicating functional redundancy in these regions. To navigate through the complexity of these association networks we mapped candidate genes and metabolites onto metabolic pathways and implemented a shortest path strategy to highlight potential mechanistic links between metabolites and transcripts at colocalized mQTLs and eQTLs. Minimizing shortest path length drove prioritization of biological validations by gene silencing. Conclusions: These results underline the importance of network-based integration of multilevel systems genetics datasets to improve understanding of the genetic architecture of metabotype and transcriptomic regulations and to characterize novel functional roles for genes determining tissue-specific metabolism